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Triglyceride Accumulation (triglyceride + accumulation)
Selected AbstractsEffects of dietary fatty acids on insulin sensitivity and secretionDIABETES OBESITY & METABOLISM, Issue 6 2004Melania Manco Globalization and global market have contributed to increased consumption of high-fat, energy-dense diets, particularly rich in saturated fatty acids( SFAs). Polyunsaturated fatty acids (PUFAs) regulate fuel partitioning within the cells by inducing their own oxidation through the reduction of lipogenic gene expression and the enhancement of the expression of those genes controlling lipid oxidation and thermogenesis. Moreover, PUFAs prevent insulin resistance by increasing membrane fluidity and GLUT4 transport. In contrast, SFAs are stored in non-adipocyte cells as triglycerides (TG) leading to cellular damage as a sequence of their lipotoxicity. Triglyceride accumulation in skeletal muscle cells (IMTG) derives from increased FA uptake coupled with deficient FA oxidation. High levels of circulating FAs enhance the expression of FA translocase the FA transport proteins within the myocites. The biochemical mechanisms responsible for lower fatty acid oxidation involve reduced carnitine palmitoyl transferase (CPT) activity, as a likely consequence of increased intracellular concentrations of malonyl-CoA; reduced glycogen synthase activity; and impairment of insulin signalling and glucose transport. The depletion of IMTG depots is strictly associated with an improvement of insulin sensitivity, via a reduced acetyl-CoA carboxylase (ACC) mRNA expression and an increased GLUT4 expression and pyruvate dehydrogenase (PDH) activity. In pancreatic islets, TG accumulation causes impairment of insulin secretion. In rat models, ,-cell dysfunction is related to increased triacylglycerol content in islets, increased production of nitric oxide, ceramide synthesis and ,-cell apoptosis. The decreased insulin gene promoter activity and binding of the pancreas-duodenum homeobox-1 (PDX-1) transcription factor to the insulin gene seem to mediate TG effect in islets. In humans, acute and prolonged effects of FAs on glucose-stimulated insulin secretion have been widely investigated as well as the effect of high-fat diets on insulin sensitivity and secretion and on the development of type 2 diabetes. [source] Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal womenDIABETES OBESITY & METABOLISM, Issue 3 2006A. D. Karelis Aim:, We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. Methods:, Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 ± 5.3 years; BMI: 32.8 ± 4.5 kg/m2) by using both the hyperinsulinaemic,euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (,1.7 mmol/l), blood pressure (,130/,85 mmHg) and fasting glucose (,6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0,1 vs. 2 vs. ,3 features of the metabolic syndrome. Results:, We found that insulin sensitivity decreased in a graded fashion (12.19 ± 3.2 vs. 11.80 ± 2.3 vs. 9.29 ± 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95 ± 1.1 vs. 3.28 ± 1.3 vs. 4.65 ± 2.2), as the number of features of the metabolic syndrome increased from 0,1 to ,3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. Conclusions:, These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship. [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] Stereospeci,c effects of catechin isomers on insulin induced lipogenesis in 3T3-L1 cellsPHYTOTHERAPY RESEARCH, Issue 6 2004Miyako Mochizuki Abstract We studied the in,uence of (+)- and (,)-catechin contained in green tea on insulin induced lipogenesis in 3T3-L1 cells. In 14 days of culture with insulin, the intracellular triglyceride concentration and the activities of glycerophosphate dehydrogenase, a marker of adipose conversion, increased. The addition of 0.02 mg/ml (+)-isomer stimulated the accumulation of triglyceride induced by insulin, but the addition of the same concentration of (,)-isomer inhibited lipogenesis. The activities of glycerophosphate dehydrogenase were changed by (+)- and (,)-catechin in the same direction as the corresponding changes in triglyceride accumulation. These data suggest a biological signi,cance of catechins, with opposite effects on lipid metabolism depending on the isomer. Copyright © 2004 John Wiley & Sons, Ltd. [source] Development of an in vitro cell culture model of hepatic steatosis using hepatocyte-derived reporter cells,BIOTECHNOLOGY & BIOENGINEERING, Issue 5 2009Amol V. Janorkar Abstract Fatty liver disease is a problem of growing clinical importance due to its association with the increasingly prevalent conditions of obesity and diabetes. While steatosis represents a reversible state of excess intrahepatic lipid, it is also associated with increased susceptibility to oxidative and cytokine stresses and progression to irreversible hepatic injury characterized by steatohepatitis, cirrhosis, and malignancy. Currently, the molecular mechanisms underlying progression of this dynamic disease remain poorly understood, particularly at the level of transcriptional regulation. We recently constructed a library of stable monoclonal green fluorescent protein (GFP) reporter cells that enable transcriptional regulation to be studied dynamically in living cells. Here, we adapt the reporter cells to create a model of steatosis that will allow investigation of transcriptional dynamics associated with the development of steatosis and the response to subsequent "second hit" stresses. The reporter model recapitulates many cellular features of the human disease, including fatty acid uptake, intracellular triglyceride accumulation, increased reactive oxygen species accumulation, decreased mitochondrial membrane potential, increased susceptibility to apoptotic cytokine stresses, and decreased proliferation. Finally, to demonstrate the utility of the reporter cells for studying transcriptional regulation, we compared the transcriptional dynamics of nuclear factor ,B (NF,B), heat shock response element (HSE), and glucocorticoid response element (GRE) in response to their classical inducers under lean and fatty conditions and found that intracellular lipid accumulation was associated with dose-dependent impairment of NF,B and HSE but not GRE activation. Thus, steatotic reporter cells represent an efficient model for studying transcriptional responses and have the potential to provide important insights into the progression of fatty liver disease. Biotechnol. Bioeng. 2009;102: 1466,1474. © 2008 Wiley Periodicals, Inc. [source] Application of Multivariate Analysis to Optimize Function of Cultured HepatocytesBIOTECHNOLOGY PROGRESS, Issue 2 2003Christina Chan Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes in intracellular pathway fluxes of primary rat hepatocytes exposed to human plasma and to provide a comprehensive snapshot of the hepatic metabolic profile. In the current study, the combination of preconditioning and plasma supplementation produced distinct metabolic states. Combining the metabolic flux distribution obtained by MFA with methodologies such as Fisher discriminant analysis (FDA) and partial least squares or projection to latent structures (PLS) provided insights into the underlying structure and causal relationship within the data. With the aid of these analyses, patterns in the cellular response of the hepatocytes that contributed to the separation of the different hepatic states were identified. Of particular interest was the recognition of distal pathways that strongly correlated with a particular hepatic function. The hepatic functions investigated were intracellular triglyceride accumulation and urea production. This study illustrates a framework for optimizing hepatic function and a possibility of identifying potential targets for improving hepatic functions. [source] | |||||||||||||