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Lipolysis
Kinds of Lipolysis Selected AbstractsFat as a fuel: emerging understanding of the adipose tissue,skeletal muscle axisACTA PHYSIOLOGICA, Issue 4 2010K. N. Frayn Abstract The early pioneers in the field of metabolism during exercise such as Lindhard and Krogh understood the importance of fat as a fuel for muscle contraction. But they could not have understood the details of the pathways involved, as neither the metabolic role of adipose tissue nor the transport role of non-esterified fatty acids (NEFA) in the plasma was clearly understood at the time. We now recognize that the onset of muscular contraction coincides with an increase in the delivery of NEFA from adipose tissue, probably coordinated by the sympatho-adrenal system. During light exercise, adipose tissue-derived NEFA make up the majority of the oxidative fuel used by muscle. As exercise is prolonged, the importance of NEFA increases. The onset of exercise is marked by an increased proportion of NEFAs entering ,-oxidation rather than re-esterification and recycling. At moderate intensities of exercise, other sources of fat, potentially plasma- and intramyocellular-triacylglycerol, supplement the supply of plasma NEFA. The delivery of NEFA is augmented by increased adipose tissue blood flow and by other stimuli such as atrial natriuretic peptide. Only during high-intensity exercise is there a failure of adipose tissue to deliver sufficient fatty acids for muscle (which is coupled with an inability of muscle to use them, even when fatty acids are supplied artificially). This limitation of adipose tissue NEFA delivery may reflect some feedback inhibition of lipolysis, perhaps via lactate, or possibly ,-adrenergic inhibition of lipolysis at very high catecholamine concentrations. [source] Ascorbic acid oral treatment modifies lipolytic response and behavioural activity but not glucocorticoid metabolism in cafeteria diet-fed ratsACTA PHYSIOLOGICA, Issue 4 2009D. F. Garcia-Diaz Abstract Aim:, To analyse the effects of vitamin C (VC), a potent dietary antioxidant, oral supplementation on body weight gain, behavioural activity, lipolytic response and glucocorticoid metabolism in the early stages of diet-induced overweight in rats. Methods:, Food intake, locomotive activity and faecal corticosterone were assessed during the 14 day trial period. After 2 weeks, the animals were sacrificed and the body composition, biochemical markers and lipolytic response from isolated adipocytes from retroperitoneal white adipose tissue were examined. Results:, The intake of a high-fat diet by rats induced a significant increase in body weight, adiposity and insulin resistance markers as well as a decrease in faecal corticosterone levels compared with standard diet-fed rats. Interestingly, the animals fed on the cafeteria diet showed a significant increase in the isoproterenol-induced lipolytic response in isolated adipocytes. Furthermore, this cafeteria-fed group showed a reduced locomotive behaviour than the control rats. On the other hand, oral VC supplementation in animals receiving the high-fat diet restored the cafeteria diet effect in some of the analysed variables such as final body weight and plasma insulin to control group levels. Remarkably, increases in locomotive behaviour and a significant decrease in the lipolytic response induced by isoproterenol on isolated adipocytes from animals treated with VC were observed. Conclusion:, This work demonstrates that an oral ascorbic acid supplementation has direct effects on behavioural activity and on adipocyte lipolysis in early obesity stages in rats, which could indicate a protective short-term role of this vitamin against adiposity induced by chronic high-fat diet consumption. [source] Pituitary and autonomic responses to cold exposures in manACTA PHYSIOLOGICA, Issue 4 2005J. Leppäluoto Abstract This review presents hormonal responses to various cold exposures and their calorigenic effects in man and some animals. Previous studies in rats have shown that cold exposures activate the hypothalamic-pituitary-thyroid axis. Increased thyroid hormone concentrations lead to heat production via general stimulation of metabolism (obligatory thermogenesis) and possibly via activation of thyroid hormone receptors and uncoupling protein 1 (UCP 1) and deiodinase enzyme genes in the brown adipose tissue (BAT). In human subjects long-term cold exposures do not seem to activate the pituitary-thyroid axis, but rather accelerate the elimination of triiodothyronine (T3), leading to low serum concentrations of free T3 hormone. In corollary to this a hypothyreotic condition with increased serum thyroid-stimulating hormone and impaired mood and cognitive performance can be observed after long-term cold exposures such as wintering. During cold exposures the sympathetic nerve system is activated and noradrenaline is released to blood circulation and to BAT, where it leads to production of cAMP, lipolysis and free fatty acids. Free fatty acids open the mitochondrial proton channel protein in BAT. Protons enter the mitochondria and inhibit ATP synthesis (uncoupling). By this way energy is transformed into heat (facultatory or adaptive thermogenesis). In adult human subjects the amount of BAT is small and adaptive thermogenesis (non-shivering thermogenesis) has a smaller role. UCP 1 with other uncoupling proteins may have other functions in the control of body weight, sugar balance and formation of reactive oxygen species. [source] Laser Lipolysis Using a Novel 1,064 nm Nd:YAG LaserDERMATOLOGIC SURGERY, Issue 2 2006KAREN H. KIM MD BACKGROUND We studied the safety and efficacy of a 1,064 nm Nd:YAG laser with a 300 ,m fiber for the reduction of small unwanted fat areas. METHODS Thirty subjects with focal areas of fat less than 100 cm3 were enrolled. Ten subjects were treated with laser lipolysis and had magnetic resonance imaging (MRI) at baseline and 3 months post-treatment. Ten subjects had laser lipolysis followed by biweekly treatments with the Tri-active system. The last group of 10 subjects served as control. Patients were seen at baseline, 1 week, 1 month, and 3 month follow-up visits. RESULTS Twenty-nine patients completed the study. Self-assessment evaluations reported an improvement of 37% at the 3-month follow-up visit. MRI demonstrated an average 17% reduction in fat volume. Smaller baseline volume areas, such as the submentum, showed better results, suggesting a dose-response relationship. The most common side effects were mild bruising and swelling resolving within 2 weeks. CONCLUSION Laser lipolysis using the 1,064 nm Nd:YAG laser with 300 ,m fiber appears to be a very promising procedure that delivers good, reproducible results safely and effectively. The advantages include excellent patient tolerance, quick recovery time, as well as the benefit of dermal tightening. [source] Comparison of the antilipolytic effects of an A1 adenosine receptor partial agonist in normal and diabetic ratsDIABETES OBESITY & METABOLISM, Issue 2 2009A. K. Dhalla Introduction and Aims:, Elevated plasma free fatty acid (FFA) concentrations play a role in the pathogenesis of type 2 diabetes (2DM). Antilipolytic agents that reduce FFA concentrations may be potentially useful in the treatment of 2DM. Our previous observation that CVT-3619 lowered plasma FFA and triglyceride concentrations in rats and enhanced insulin sensitivity in rodents with dietary-induced forms of insulin resistance suggested that it might be of use in the treatment of patients with 2DM. The present study was undertaken to compare the antilipolytic effects of CVT-3619 in normal (Sprague Dawley, SD) and Zucker diabetic fatty (ZDF) rats. Results:, ZDF rats had significantly higher fat pad weight, glucose, insulin and FFA concentrations than those of SD rats. EC50 values for forskolin-stimulated FFA release from isolated adipocytes from SD and ZDF rats were 750 and 53 nM, respectively (p < 0.05). Maximal forskolin stimulation of FFA release was significantly (p < 0.01) less in ZDF rats (133 ± 60 ,M) compared with SD rats (332 ± 38 ,M). EC50 values for isoproterenol to increase lipolysis in adipocytes from SD and ZDF rats were 2 and 7 nM respectively. Maximal isoproterenol-stimulated lipolysis was significantly (p < 0.01) lower in adipocytes from ZDF rats (179 ± 23 ,M) compared with SD rats (343 ± 27 ,M). Insulin inhibited lipolysis in adipocytes from SD rats with an IC50 value of 30 pM, whereas adipocytes from ZDF rats were resistant to the antilipolytic actions of insulin. In contrast, IC50 values for CVT-3619 to inhibit the release of FFA from SD and ZDF adipocytes were essentially the same (63 and 123 nM respectively). CVT-3619 inhibited lipolysis more than insulin in both SD (86 vs. 46%, p < 0.001) and ZDF (80 vs. 13%, p < 0.001) adipocytes. In in vivo experiments, CVT-3619 (5 mg/kg, PO) lowered FFA to a similar extent in both groups. Plasma concentrations of CVT-3619 were not different in SD and ZDF rats. There was no significant difference in the messenger RNA expression of the A1 receptors relative to ,-actin expression in adipocytes from SD (0.98 ± 0.2) and ZDF rats (0.99 ± 0.3). Conclusion:, The antilipolytic effects of CVT-3619 appear to be independent of insulin resistance and animal model. [source] Administration of myostatin does not alter fat mass in adult miceDIABETES OBESITY & METABOLISM, Issue 2 2008L. E. Stolz Aim: Myostatin, a member of the TGF-beta superfamily, is produced by skeletal muscle and acts as a negative regulator of muscle mass. It has also been suggested that low-dose administration of myostatin (2 ,g/day) in rodents can reduce fat mass without altering muscle mass. In the current study, we attempted to further explore the effects of myostatin on adipocytes and its potential to reduce fat mass, since myostatin administration could potentially be a useful strategy to treat obesity and its complications in humans. Methods: Purified myostatin protein was examined for its effects on adipogenesis and lipolysis in differentiated 3T3-L1 adipocytes as well as for effects on fat mass in wild-type, myostatin null and obese mice. Results: While myostatin was capable of inhibiting adipogenesis in 3T3-L1 cells, it did not alter lipolysis in fully differentiated adipocytes. Importantly, pharmacological administration of myostatin over a range of doses (2,120 ,g/day) did not affect fat mass in wild-type or genetically obese (ob/ob, db/db) mice, although muscle mass was significantly reduced at the highest myostatin dose. Conclusions: Our results suggest that myostatin does not reduce adipose stores in adult animals. Contrary to prior indications, pharmacological administration of myostatin does not appear to be an effective strategy to treat obesity in vivo. [source] Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adultsDIABETES OBESITY & METABOLISM, Issue 1 2007K. C. J. Yuen Growth hormone (GH) is generally considered to exert anti-insulin actions, whereas insulin-like growth factor I (IGF-I) has insulin-like properties. Paradoxically, GH deficient adults and those with acromegaly are both predisposed to insulin resistance, but one cannot extrapolate from these pathological conditions to determine the normal metabolic roles of GH and IGF-I on glucose homeostasis. High doses of GH treatment have major effects on lipolysis, which plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as an insulin sensitizer that does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is only evident after feeding when the bioavailability of circulating IGF-I is increased. In contrast, many studies in GH deficient adults have consistently shown that GH replacement improves the body composition profile although these studies differ considerably in terms of age, the presence or absence of multiple pituitary hormone deficiency, and whether GH deficiency was childhood or adult-onset. However, the improvement in body composition does not necessarily translate into improvements in insulin sensitivity presumably due to the anti-insulin effects of high doses of GH therapy. More recently, we have found that a very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without affecting body composition in GH-deficient adults and in subjects with metabolic syndrome, and we postulate that these effects are mediated by its ability to increase free ,bioavailable' IGF-I without the induction of lipolysis. These results raise the possibility that this low GH dose may play a role in preventing the decline of ,-cell function and the development of type 2 diabetes in these "high risk" subjects. [source] Diabetes: insulin resistance and derangements in lipid metabolism.DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2005Cure through intervention in fat transport, storage Abstract We present multiple findings on derangements in lipid metabolism in type 2 diabetes. The increase in the intracellular deposition of triglycerides (TG) in muscles, liver and pancreas in subjects prone to diabetes is well documented and demonstrated to attenuate glucose metabolism by interfering with insulin signaling and insulin secretion. The obesity often associated with type 2 diabetes is mainly central, resulting in the overload of abdominal adipocytes with TG and reducing fat depot capacity to protect other tissues from utilizing a large proportion of dietary fat. In contrast to subcutaneous adipocytes, the central adipocytes exhibit a high rate of basal lipolysis and are highly sensitive to fat mobilizing hormones, but respond poorly to lipolysis restraining insulin. The enlarged visceral adipocytes are flooding the portal circulation with free fatty acids (FFA) at metabolically inappropriate time, when FFA should be oxidized, thus exposing nonadipose tissues to fat excess. This leads to ectopic TG accumulation in muscles, liver and pancreatic beta-cells, resulting in insulin resistance and beta-cell dysfunction. This situation, based on a large number of observations in humans and experimental animals, confirms that peripheral adipose tissue is closely regulated, performing a vital role of buffering fluxes of FFA in the circulation. The central adipose tissues tend to upset this balance by releasing large amounts of FFA. To reduce the excessive fat outflow from the abdominal depots and prevent the ectopic fat deposition it is important to decrease the volume of central fat stores or increase the peripheral fat stores. One possibility is to downregulate the activity of lipoprotein lipase, which is overexpressed in abdominal relatively to subcutaneous fat stores. This can be achieved by gastrointestinal bypass or gastroplasty, which decrease dietary fat absorption, or by direct means that include surgical removal of mesenteric fat. Indirect treatment consists of the compliant application of drastic lifestyle change comprising both diet and exercise and pharmacotherapy that reduces mesenteric fat mass and activity. The first step should be an attempt to effectively induce a lifestyle change. Next comes pharmacotherapy including acarbose, metformin, PPAR,, or PPAR,, agonists, statins and orlistat, estrogens in postmenopausal women or testosterone in men. Among surgical procedures, gastric bypass has been proven to produce beneficial results in advance of other surgical techniques, the evidence basis of which still needs strengthening. Copyright © 2004 John Wiley & Sons, Ltd. [source] An adipocentric view of signaling and intracellular traffickingDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2002Silvia Mora Abstract Adipocytes have traditionally been considered to be the primary site for whole body energy storage mainly in the form of triglycerides and fatty acids. This occurs through the ability of insulin to markedly stimulate both glucose uptake and lipogenesis. Conventional wisdom held that defects in fuel partitioning into adipocytes either because of increased adipose tissue mass and/or increased lipolysis and circulating free fatty acids resulted in dyslipidemia, obesity, insulin resistance and perhaps diabetes. However, it has become increasingly apparent that loss of adipose tissue (lipodystrophies) in both animal models and humans also leads to metabolic disorders that result in severe states of insulin resistance and potential diabetes. These apparently opposite functions can be resolved by the establishment of adipocytes not only as a fuel storage depot but also as a critical endocrine organ that secretes a variety of signaling molecules into the circulation. Although the molecular function of these adipocyte-derived signals are poorly understood, they play a central role in the maintenance of energy homeostasis by regulating insulin secretion, insulin action, glucose and lipid metabolism, energy balance, host defense and reproduction. The diversity of these secretory factors include enzymes (lipoprotein lipase (LPL) and adipsin), growth factors [vascular endothelial growth factor (VEGF)], cytokines (tumor necrosis factor-,, interleukin 6) and several other hormones involved in fatty acid and glucose metabolism (leptin, Acrp30, resistin and acylation stimulation protein). Despite the large number of molecules secreted by adipocytes, our understanding of the pathways and mechanisms controlling intracellular trafficking and exocytosis in adipocytes is poorly understood. In this article, we will review the current knowledge of the trafficking and secretion processes that take place in adipocytes, focusing our attention on two of the best characterized adipokine molecules (leptin and adiponectin) and on one of the most intensively studied regulated membrane proteins, the GLUT4 glucose transporter. Copyright © 2002 John Wiley & Sons, Ltd. [source] Insulin resistance in type 2 diabetes: role of fatty acids,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002Peter Arner Abstract Insulin resistance is one of the key factors responsible for hyperglycaemia in type 2 diabetes and can result in a number of metabolic abnormalities associated with cardiovascular disease (insulin resistance syndrome), even in the absence of overt diabetes. The mechanisms involved in the development of insulin resistance are multifactorial and are only partly understood, but increased availability of free fatty acids (FFAs) is of particular importance for the liver and skeletal muscle. The role of FFAs in type 2 diabetes is most evident in obese patients who have several abnormalities in FFA metabolism. Because of a mass effect, the release of FFAs from the total adipose tissue depot to the blood stream is increased and the high concentration of circulating FFAs impairs muscle uptake of glucose by competitive inhibition. In upper-body obesity, which predisposes individuals to type 2 diabetes, the rate of lipolysis is accelerated in visceral adipose tissue. This results in a selective increase in FFA mobilisation to the portal vein, which connects visceral fat to the liver. A high ,portal' FFA concentration has undesirable effects on the liver, resulting in dyslipidaemia, hyperinsulinaemia, hyperglycaemia and hepatic insulin resistance. Recently, a new class of antidiabetic agents, the thiazolidinediones (TZDs) or ,glitazones' has been developed. A prominent effect of these agents is the lowering of circulating FFA levels and it is believed, but not yet proven, that this interaction with FFAs constitutes a major mechanism behind the glucose-lowering effect of the TZDs. Copyright © 2002 John Wiley & Sons, Ltd. [source] Studies of associations between the Arg389Gly polymorphism of the ,1 -adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjectsDIABETIC MEDICINE, Issue 4 2007A. P. Gjesing Abstract Aims, Activation of the ,1 -adrenergic receptor (ADRB1) causes increased lipolysis in adipose tissue and enhances cardiac output. Analysis of the association of the functional ADRB1 Arg389Gly variant with obesity and hypertension has given ambiguous results. To clarify the potential impact of this variant on obesity and hypertension in the general population, we examined the Arg389Gly variant in a relatively large-scale population-based study. Methods, Case-control studies and quantitative trait analyses were carried out in 7677 Danish Caucasians who were genotyped for the Arg389Gly variant (dbSNP rs1801253) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results, A weak association between the Gly allele of the Arg389Gly variant and obesity was observed when comparing cases (n = 1540) defined as body mass index (BMI) > 30 kg/m2 with control subjects (n = 6108) defined as BMI , 30 kg/m2 for both allele frequencies (P = 0.05) and genotype distribution (P = 0.05). Case-control studies (cases n = 2518; control n = 3981) examining the effect on hypertension showed no association with allele frequencies (P = 0.3) or genotype distribution (P = 0.5); however, in the quantitative trait analyses, individuals carrying the Gly allele had slightly but significantly lower diastolic (Arg/Arg = 81.9 mmHg vs. Gly-allele carriers = 81.5 mmHg) and systolic (Arg/Arg = 129.4 mmHg vs. Gly-allele carriers = 128.8 mmHg) blood pressure as well as a lower mean arterial blood pressure. Conclusion, Our results suggest that the Arg389Gly polymorphism does not have any clinically important impact on the pathogenesis of obesity in Danish white subjects. Furthermore, despite the observed minor influence on blood pressure, this variant is most likely not to be a major contributor to the development of hypertension. [source] Insulino-mimetic and anti-diabetic effects of vanadium compoundsDIABETIC MEDICINE, Issue 1 2005A. K. Srivastava Abstract Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes. [source] The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young menDIABETIC MEDICINE, Issue 6 2003J. R. Ortlepp Abstract Aims Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor (VDR), which has been found to be associated with bone mineral density, has been reported to be also associated with Type 2 diabetes mellitus (DM). To test the influence of the VDR polymorphism on fasting glucose in healthy young men before the onset of Type 2 DM, we studied a homogeneous population of aircrew members. Methods A total of 1539 individuals were recruited during routine medical qualification for flying duty. Physical activity was assessed in all individuals and categorized into low physical activity (, 3 h per week) and high physical activity (> 3 h per week). The BsmI VDR polymorphism was analysed by polymerase chain reaction. On the day of blood testing the individuals were fasting for at least 8 h overnight. Serum glucose was measured within 60 min after sampling venous blood. Results In young males with low physical activity (n = 752) gene carriers with the VDR genotype BB (n = 137) have significantly (P < 0.001) higher levels of fasting glucose (5.61 ± 0.49 mmol/l) than gene carriers with the genotype Bb (n = 370; 5.44 ± 0.44 mmol/l) or bb (n = 245; 5.38 ± 0.44 mmol/l). Of BB gene carriers, 47% had fasting glucose levels > 5.55 mmol/l compared with 36% of Bb gene carriers and 34% of bb gene carriers (P = 0.018). This effect is absent in gene carriers with high physical activity (n = 787). Conclusions The VDR genotype is associated with altered fasting glucose levels in young men with low physical activity. If this association is confirmed in other populations it might be worthwhile studying the particular benefits of an exercise programme in dependents of the VDR genotype. Diabet. Med. 20, 451,454 (2003) [source] The vitamin D receptor gene variant is associated with the prevalence of Type 2 diabetes mellitus and coronary artery diseaseDIABETIC MEDICINE, Issue 10 2001J. R. Ortlepp Abstract Aims, Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor, which has been found to be associated with bone mineral density, has also been reported to be associated with insulin-dependent diabetes mellitus. To test the influence of the vitamin D receptor polymorphism on the prevalence of Type 2 diabetes mellitus and coronary artery disease we studied a population of high-risk patients, who were referred to our clinic for diagnostic coronary angiography. Methods, A total of 293 patients considered at high risk for coronary artery disease because of angina pectoris and known hypercholesterolaemia underwent diagnostic coronary angiography. The BsmI vitamin D receptor polymorphism was analysed by polymerase chain reaction. Results, Prevalence of Type 2 diabetes mellitus and coronary artery disease was gradually dependent on the number of B alleles (BB 28%, Bb 13%, bb 8% for Type 2 diabetes mellitus, P = 0.002; BB 88% Bb 72%, bb 66% coronary artery disease, P = 0.01). Patients with the BB genotype had an odds ratio of 3.64 (95% confidence interval 1.53,8.55, P = 0.002) to have Type 2 diabetes mellitus compared with patients with the bb genotype. Conclusions, The genotype of the vitamin D receptor polymorphism determines the prevalence of Type 2 diabetes mellitus and coronary artery disease in a high-risk cohort population. Diabet. Med. 18, 842,845 (2001) [source] Postprandial interstitial insulin concentrations in type 2 diabetes relativesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006M. Sandqvist Abstract Background, An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. Subjects and methods, Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. Results, The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 ± 3032 vs. Plac 4682 ± 2613 pmol L,1 min; P < 0·05, mean ± SE]. However, the postprandial I-insulinmax/P-insulinmax ratio was similar on the two test days (nateglinide: 213 ± 62 vs. 501 ± 92 pmol L,1, I/P-ratio: 0·38 ± 0·06 and placebo: 159 ± 39 vs. 410 ± 74 pmol L,1, I/P-ratio: 0·36 ± 0·05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. Conclusions, Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients. [source] Quantitative modeling of triacylglycerol homeostasis in yeast , metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growthFEBS JOURNAL, Issue 22 2008Jürgen Zanghellini Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quantitatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. By combining dynamic mass balances for key metabolites with a detailed steady-state analysis, we trained a model network and simulated the time-dependent degradation of cellular triacylglycerol and its interaction with fatty acid and membrane lipid synthesis. This approach described precisely, both qualitatively and quantitatively, the time evolution of various key metabolites in a consistent and self-contained manner, and the predictions were found to be in excellent agreement with experimental data. We showed that, during pre-logarithmic growth, lipolysis of triacylglycerol allows for the rapid synthesis of membrane lipids, whereas de novo fatty acid synthesis plays only a minor role during this growth phase. Progress in triacylglycerol hydrolysis directly correlates with an increase in cell size, demonstrating the importance of lipolysis for supporting efficient growth initiation. [source] Structural and compositional changes in very low density lipoprotein triacylglycerols during basal lipolysisFEBS JOURNAL, Issue 24 2002Jyrki J. Ågren Triacylglycerols secreted by liver and carried by very low density lipoprotein (VLDL) are hydrolysed in circulation by lipoprotein and hepatic lipases. These enzymes have been shown to have positional and fatty acid specificity in vitro. If there were specificity in basal lipolysis in vivo, triacylglycerol compositions of circulating and newly secreted VLDL would be different. To study this we compared the composition of normal fasting VLDL triacylglycerol of Wistar rats to that obtained after blocking lipolysis by Triton WR1339, which increased plasma VLDL triacylglycerol concentration about 4.7-fold in 2 h. Analyses of molecular species of sn -1,2- and sn -2,3-diacylglycerol moieties and stereospecific triacylglycerol analysis revealed major differences between the groups in the VLDL triacylglycerol composition. In nontreated rats, the proportion of 16:0 was higher and that of 18:2n-6 lower in the sn -1 position. The proportion of 14:0 was lower in all positions and that of 18:0 was lower in the sn -1 and sn -3 positions in nontreated rats whereas the proportions of 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3 were higher in the sn -1 and lower in the sn -2 position. These results suggest that the fatty acid of the sn -1 position is the most decisive factor in determining the sensitivity for hydrolysis of the triacylglycerol. In addition, triacylglycerol species with highly unsaturated fatty acids in the sn -2 position also favoured hydrolysis. The in vivo substrate specificity followed only partly that obtained in in vitro studies indicating that the nature of molecular association of fatty acids in natural triacylglycerol affects its susceptibility to lipolysis. To conclude, our results indicate that preferential basal lipolysis leads to major structural differences between circulating and newly secreted VLDL triacylglycerol. These differences extend beyond those anticipated from analysis of total fatty acids and constitute a previously unrecognized feature of VLDL triacylglycerol metabolism. [source] Abstracts: The effects of Coptis japonica root extract and its key component, berberine, on human subcutaneous adipocytesINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2010Keiko Yashiki(Tohi) pp.274,280 An increase of subcutaneous fat presses lymph vessels and blood vessels in skin tissues, and results in not only causing skin troubles such as skin sagging and swelling but also forming cellulite that makes bodylines worse. To expand further application of plant extracts to cosmetics, we focused on inhibitory effects of subcutaneous preadipocytes differentiation and facilitating lipolysis in adipocytes. In this study, in a screening test of a number of plant extracts, Coptis japonica root extract and its key component, berberine, showed potent inhibition of triglyceride accumulation and subcutaneous preadipocytes differentiation. Furthermore, Coptis japonica root extract and berberine down-regulated the mRNA expression level of several differentiation factors derived from subcutaneous preadipocytes. Coptis japonica root extract and berberine in subcutaneous adipocytes facilitated lipolysis in mature adipocytes. Our study suggested that Coptis japonica root extract and its key component, berberine, is expected to be useful for slimming and related skin troubles such as skin sagging, swelling, cellulite, and so on. [source] The penetration enhancement and the lipolytic effects of TAT,GKH, both in in vitro, ex vivo, and in vivoINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2004J. Lim It was demonstrated that the trans-activating transcriptional activator (TAT) protein from HIV-1 could enter cells when added to the surrounding media. TAT peptide chemically attached to various proteins was able to deliver these proteins to various cells and even at high levels in heart and spleen tissues in mice. In this study, the tri-peptide GKH (glycine,lysine,histidine) derived from the parathyroid hormone, which is known as a lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient for eye-bag care product. When glycerol is released, expressed as the extracellular glycerol concentration (the so-called lipolysis index), TAT,GKH at 10,5m induces a maximal lipolytic effect of approximately 41.5% in epididymal adipocytes isolated from rats, compared with basal lipolysis. In a microdialysis study, TAT,GKH was perfused into epididymal adipose tissues of anaesthetized rats in increasing concentrations in a Ringer solution. The glycerol concentration in each dialysate was measured using an ultra-sensitive radiometric method. The perfusion of TAT,GKH induced a lipolytic effect. A penetration study showed that TAT,GKH resulted in a sevenfold higher penetration into excised hairless mice skin than GKH. An in vivo study showed that a TAT,GKH containing emulsion had a better effect upon the relative volume reduction of eye bag after 28 days of application on 22 healthy female volunteers than the placebo. It was therefore concluded that TAT,GKH increased skin penetration, which resulted in enhanced lipolytic effects in in vitro, ex vivo and in volume reduction of eye-bags in in vivo studies. [source] Effect of somatic cell counts on lipolysis, proteolysis and apparent viscosity of UHT milk during storageINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 4 2008ANDREZZA M FERNANDES In this work, lipolysis, proteolysis and viscosity of ultra-high temperature (UHT) milk containing different somatic cell counts (SCC) were investigated. UHT milks were analysed on days 8, 30, 60, 90 and 120 of storage. Lipolysis as measured by free fatty acids increase, casein degradation and viscosity of UHT milk were not affected by SCC but increased during storage. A negative relationship was observed between SCC and casein as a percentage of true protein on the 120th day of storage, hence indicating that high SCC increases the proteolysis of UHT milk by the end of its shelf life. [source] Ripening of traditional Örgü cheese manufactured with raw or pasteurized milk: Composition and biochemical propertiesINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 4 2007SERAFETTIN CELIK The changes in composition and some biochemical properties of Örgü cheeses made from raw (RMC) and pasteurized (PMC) cow milk were investigated during a 90-day ripening period. The average contents of total solids (TS), protein, water soluble nitrogen (WSN), trichloro-acetic acid soluble nitrogen (TCA-SN) and acid degree value (ADV) were lower, while salt and salt in TS were found to be statistically higher in PMC than RMC (P < 0.05). In addition, in both RMC and PMC, the TS and protein contents were decreased as compared to an increase in salt, salt in TS, WSN and TCA-SN contents, and ADV, during ripening (P < 0.05). The evaluation of WSN, TCA-SN and ADV shows that these two experimental Örgü cheese types undergo little proteolysis and lipolysis. On the other hand, acidity development was observed to be high in both before curdling and in cheese made from raw milk during ripening. [source] Influence of composition on the biochemical and sensory characteristics of commercial Cheddar cheese of variable quality and fat contentINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 2 2007K N KILCAWLEY Ten commercial Cheddar cheeses of variable quality differing in fat content and age were subjected to compositional, proteolytic, lipolytic and sensory analyses. The compositional parameters of the full-fat cheeses were predominantly outside those typically associated with good-quality cheese. Sensory analysis discriminated the full-fat cheeses predominantly by age, with the longer ripened cheeses associated with more negative attributes, some which appeared to be due to excessive lipolysis and/or ,-casein breakdown. Both proteolysis and lipolysis appear to be age dependent. The two reduced-fat cheeses were clearly discriminated from the eight full-fat cheeses by sensory analysis that appeared to be due to differences in composition and the extent of lipolysis. [source] Effect of hydrogen peroxide treatment on the quality of raw creamINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 3 2000BARBAROS OZER The effect of hydrogen peroxide on the attributes of raw cream was studied. The samples with 500 mg/kg and 1500 mg/kg hydrogen peroxide (H2O2) were compared with an untreated control sample. The results indicated that the addition of hydrogen peroxide prevented, to a great extent, the development of lipolysis, proteolysis and acidity, as well as the growth of psychrotrophic microorganisms. However, the treatment had a negative effect on the oxidative stability of the cream. [source] Effect of using interesterified and non-interesterified corn and palm oil blends on quality and fatty acid composition of Turkish White cheeseINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 12 2007Issa Javidipour Summary Chemically interesterified blends (CIB) and non-interesterified blends (NIB) of corn and palm oils (75%w/25%w) were studied in the production of Turkish White cheese (TWC) to modify the fatty acid composition of traditional product. Milk fat (3%) was replaced by CIB and NIB for 25%, 50%, 75% and 100%. All cheese groups were ripened at 5 °C for 90 days. Samples were taken from each group after 3, 30, 60 and 90 days and analysed for their basic composition, lipolysis and proteolysis. CIB-incorporated cheeses showed a higher degree of lipolysis than the control sample and the NIB-incorporated counterparts. Fatty acid composition and sensory properties of the final product showed that the incorporation of CIB and NIB in TWC improved the nutritional content of the product because it altered the fatty acid composition without any adverse effect on sensorial quality. We concluded that in production of TWC, 50% of milk fat could be successfully replaced with CIB and NIB, preferably CIB, because of its superior sensory quality. [source] Adipose tissue gene expression in obese dogs after weight lossJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2008V. Leray Summary Body weight (BW) mainly depends on a balance between fat storage (lipogenesis) and fat mobilization (lipolysis) in adipocytes. BW changes play a role in insulin resistance (IR), the inability of insulin target tissue to respond to physiological levels of insulin. This results in inhibition of lipogenesis and stimulation of lipolysis. Weight gain leads to IR whereas, weight loss improves insulin sensitivity (IS). The aim of this study was to evaluate the effect of weight loss and recovery of IS on the expression of genes involved in lipogenesis and lipolysis in weight losing dogs. Gene expression was studied in both subcutaneous and visceral adipose tissue. Obese dogs received a hypoenergetic low fat high protein diet (0.6 × NRC recommendation). Before and after weight loss, IS was assessed using the euglycaemic hyperinsulinaemic clamp. Gene expression of IRS-2, SREBP, intracellular insulin effectors, ACC, FAS, FABP, ADRP, PEPCK, lipogenesis key proteins, perilipin and HSL, lipolysis key proteins were quantified using real-time RT-PCR in subcutaneous and visceral fat. BW decreased from 15.2 ± 0.5 to 11.4 ± 0.4 kg (p < 0.05) over 78 ± 8 days. When obese, dogs were insulin resistant. After weight loss, IS was improved. In the subcutaneous adipose tissue, the expression of only the IRS-2 was increased. In the visceral adipose tissue, the expression of the genes involved in the lipogenesis was decreased whereas one of the genes implied in the lipolysis did not change. The expression profile of genes involved in lipid metabolism, as measured after weight loss, is indicative for a lower lipogenesis after weight loss than in obese dogs. Our results also confirm dramatic differences in the lipid metabolism of visceral and subcutaneous fat. They should be completed by comparing gene expression during weight losing and normal weight steady state. [source] In vivo metabolic effects of naringenin in the ethanol consuming rat and the effect of naringenin on adipocytes in vitroJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2007K. Szkudelska Summary Naringenin is a bioactive flavanone involved in the inhibition of drug metabolism which exhibits antioxidant, anti-inflammatory and anticancerogenic properties and which recently appeared to be a factor mitigating the hyperlipidaemic effects in rats and rabbits. In the performed experiment, the effect of naringenin, administered intragastrically (50 mg/kg) for 2 weeks to normal and ethanol drinking rats, on insulin and leptin levels and on some metabolic parameters was investigated. Naringenin did not change the hormone levels in any group of rats. Blood glucose, triglyceride, total, esterified and free cholesterol and high-density lipoprotein-cholesterol concentrations were also unaffected by this compound. Only free fatty acids were elevated after the naringenin treatment in the water-drinking rats. In spite of unchanged glucose and insulin concentrations in blood, the tested flavanone reduced the glucose/insulin ratio in ethanol-receiving rats. Liver triglycerides, elevated due to ethanol ingestion, were partially normalized by naringenin. Other tested parameters like liver glycogen and cholesterol, muscle triglycerides and glycogen were not altered in any group of rats. The influence of naringenin (62.5, 125, 250 and 500 ,m) on basal and insulin-stimulated glucose conversion to lipids (lipogenesis) as well as on basal and epinephrine-stimulated glycerol release (lipolysis) in the isolated rat adipocytes was also tested. The basal and the stimulated lipogenesis tended to be decreased in the presence of the flavanone (250 ,m). This inhibitory effect intensified and was statistically significant at the highest concentration of naringenin. The tested compound did not evoke any effect on basal lipolysis while the epinephrine-stimulated process was limited at the highest concentration of the flavanone. Naringenin (62.5, 125, 250 and 500 ,m) had no effect on leptin secretion from the isolated rat adipocytes. Results obtained in our studies demonstrate that naringenin exerts a very weak influence on carbohydrate and lipid metabolism of normal and ethanol-consuming rats and on metabolism of isolated rat adipocytes. [source] Zinc deficiency and activities of enzymes involved in lipogenesis and lipolysis in rats fed diets with coconut oil or fish oilJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2000K. Eder [source] Studies on the cell treatment conditions to elicit lipolytic responses from 3T3-L1 adipocytes to TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxinJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Wen Li Abstract Wasting syndrome is one of the hallmark symptoms of poisoning by TCDD (=dioxin), which is associated with the massive loss of adipose tissue and serum hyperlipidemia in vivo. Yet, the most widely used in vitro cell model 3T3-L1 adipocyte has not been useful for studying such an action of TCDD because of the difficulty of inducing their mature adipocytes to respond to TCDD to go through lipolysis. Here, we made efforts to find the right cell culture and treatment conditions to induce mature 3T3-L1 adipocytes to go through lipolysis, which is defined as events leading to reduction of lipids in adipocytes. The optimum condition was found to require 7-day differentiated adipocytes being subjected to DMEM medium containing TCDD (but without insulin) for 5 day incubation with two medium changes (the same composition) on incubation days 2 and 4. After 24 h, the early effect of TCDD on adipocytes was predominantly on inflammation, particularly induction of COX-2 and KC (IL-8), which is accompanied by upregulation of C/EBP, and ,. The sign of TCDD-induced lipolysis starts slowly and by incubation day 3, a few markers showed modestly significant changes. By day 5 of incubation, however, many markers show highly significant signs of lipolytic changes. Although this process could take place without exogenous macrophages or their cytokines, addition of exogenous TNF, considerably synergized this action of TCDD. In conclusion, under a right condition, 3T3-L1 adipocytes were found to respond to TCDD to go through lipolysis. The early trigger of such a response appears to be activation of COX-2, which is amplified by TNF,. J. Cell. Biochem. 102: 389,402, 2007. © 2007 Wiley-Liss, Inc. [source] TNF-, induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes,,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2003Sandra C. Souza Abstract Tumor necrosis factor-, (TNF-,) increases adipocyte lipolysis after 6,12 h of incubation. TNF-, has been demonstrated to activate mitogen-activated protein (MAP) kinases including extracellular signal-related kinase (ERK) and N-terminal-c-Jun-kinase (JNK) in different cell types. To determine if the MAP kinases have a role in TNF-,-induced lipolysis, 3T3-L1 adipocytes were treated with the cytokine (10 ng/ml), in the presence or absence of PD98059 or U0126 (100 µM), specific inhibitors of ERK activity. We demonstrated that U0126 or PD98059 blocked TNF-,-induced ERK activity and decreased TNF-,-induced lipolysis by 65 or 76% respectively. The peroxisome-proliferator-activated receptor , (PPAR,) agonists, rosiglitazone (ros), and 15-deoxy-,- 12,14 - prostaglandin J2 (PGJ2) have been demonstrated to block TNF-,-induced lipolysis. Pretreatment of adipocytes with these agents almost totally blocked TNF-,-induced ERK activation and reduced lipolysis by greater than 90%. TNF-, also stimulated JNK activity, which was not affected by PD98059 or PPAR, agonist treatment. The expression of perilipin, previously proposed to contribute to the mechanism of lipolysis, is diminished in response to TNF-, treatment. Pretreatment of adipocytes with PD98059 or ros significantly blocked the TNF-,-induced reduction of perilipin A protein level as determined by Western analysis. These data suggest that activation of the ERK pathway is an early event in the mechanism of TNF-,-induced lipolysis. © 2003 Wiley-Liss, Inc. [source] Injectable lipolysis: speculation vs. scienceJOURNAL OF COSMETIC DERMATOLOGY, Issue 4 2006Adam M Rotunda MD [source] | |||||||||||||||||||||||||||||||||||||