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Body Weight Reduction (body + weight_reduction)
Selected AbstractsDevelopment of the Thyroid Hormone Receptor ,-Subtype Agonist KB-141 : A Strategy for Body Weight Reduction and Lipid Lowering with Minimal Cardiac Side EffectsCARDIOVASCULAR THERAPEUTICS, Issue 2 2005Gary J. Grover ABSTRACT Few treatments for obesity exist and improvements for treatment of hyperlipidemia are still desirable. Thyroid hormone receptors (TRs) regulate body weight, adiposity, and cholesterol levels. However, thyroid hormones can have deleterious effects, particularly cardiac acceleration, that limits the use of hormones in the treatment of obesity. There is evidence that the TR, subtype mediates lowering of blood cholesterol levels and possibly elevation of metabolic rate, whereas TR, appears to control heart rate. In studies, described in this review article, we examined the effects of selective TR, activation on metabolic rate and heart rate in mice, rats and monkeys. T3 had a greater effect on increasing heart rate in wild type (WT) than in TR,-/- mice (ED15 values of 34 and 469 nmol/kg/day, respectively). T3 increased metabolic rate (MVO2) in both WT and TR,-/- mice, but the effect on TR,-/- mice was less pronounced compared to WT mice. Stimulation of MVO2 is mediated by both TR, and TR,, but with different profiles. In cholesterol-fed rats, KB-141, a selective TR, agonist, increased MVO2 with a 10-fold selectivity and lowered cholesterol with a 27-fold selectivity vs. tachycardia. In primates, KB-141 caused significant, cholesterol, Lp(a) and body weight reduction after 1 week of treatment with no effect on heart rate. These data suggest that selective TR, agonists may represent a novel class of drugs for the treatment of obesity, hypercholesterolemia and elevated Lp(a), which may make them useful therapeutics for patients with metabolic syndrome. [source] Exenatide: a review from pharmacology to clinical practiceDIABETES OBESITY & METABOLISM, Issue 6 2009R. Gentilella Background:, Exenatide is an incretin mimetic that activates glucagon-like-peptide-1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose-dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying. Methods:, In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c ,11%), or by thiazolidinediones (with or without metformin) and treated for periods from 16 weeks to 3 years, exenatide (5 ,g b.i.d. s.c. for the first 4 weeks of treatment and 10 ,g b.i.d. s.c. thereafter) reduced HbA1c, fasting and postprandial glucose, and body weight dose dependently, and was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c. Body weight diminished with exenatide, whereas it increased with both insulin preparations. Positive effects on the lipid profile and a reduction in C-reactive protein were also recorded with exenatide. Treatment extensions up to 3 years showed that benefits were maintained in the long term. Adverse events were usually mild to moderate in intensity, and generally the frequency decreased with continued therapy. The most common was nausea (whose incidence may be reduced by gradual dose escalation from 5 ,g b.i.d. to 10 ,g b.i.d.), vomiting, diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated with a sulphonylurea). Results and conclusions:, Exenatide is a new, promising therapeutic option for type 2 diabetic patients inadequately controlled by oral agents, before insulin therapy, offering the added benefits of body weight reduction and tight postprandial glucose control. [source] Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss,HEPATOLOGY, Issue 4 2009Nathan A. Johnson Weight loss remains the most common therapy advocated for reducing hepatic lipid in obesity and nonalcoholic fatty liver disease. Yet, reduction of body weight by lifestyle intervention is often modest, and thus, therapies which effectively modulate the burden of fatty liver but are not contingent upon weight loss are of the highest practical significance. However, the effect of aerobic exercise on liver fat independent of weight loss has not been clarified. We assessed the effect of aerobic exercise training on hepatic, blood, abdominal and muscle lipids in 19 sedentary obese men and women using magnetic resonance imaging and proton magnetic resonance spectroscopy (1H-MRS). Four weeks of aerobic cycling exercise, in accordance with current physical activity guidelines, significantly reduced visceral adipose tissue volume by 12% (P < 0.01) and hepatic triglyceride concentration by 21% (P < 0.05). This was associated with a significant (14%) reduction in plasma free fatty acids (P < 0.05). Exercise training did not alter body weight, vastus lateralis intramyocellular triglyceride concentration, abdominal subcutaneous adipose tissue volume, 1H-MRS,measured hepatic lipid saturation, or HOMA-IR (homeostasis model assessment of insulin resistance; P > 0.05). Conclusion: These data provide the first direct experimental evidence demonstrating that regular aerobic exercise reduces hepatic lipids in obesity even in the absence of body weight reduction. Physical activity should be strongly promoted for the management of fatty liver, the benefits of which are not exclusively contingent upon weight loss. (HEPATOLOGY 2009.) [source] Comparative study between the effect of the peroxisome proliferator activated receptor-, ligands fenofibrate and n-3 polyunsaturated fatty acids on activation of 5,-AMP-activated protein kinase-,1 in high-fat fed ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2009Tarek M. Kamal Motawi Abstract Objectives Obesity is a risk factor for type 2 diabetes mellitus. It results from an energy imbalance in which energy intake exceeds energy expenditure. The cellular fuel gauge 5,-AMP-activated protein kinase (AMPK) is a heterotrimeric protein consisting of one catalytic subunit (,) and two non-catalytic subunits (, and ,), and approximately equal levels of ,1 and ,2 complexes are present in the liver. AMPK regulates metabolic pathways in response to metabolic stress and in particular ATP depletion to switch on energy-producing catabolic pathways such as ,-oxidation of fatty acids and switch off energy-depleting processes such as synthesis of fatty acid and cholesterol. A high-fat diet alters AMPK-,1 gene expression in the liver and skeletal muscle of rats and results in body weight gain and hyperglycaemia. The aim of this study was to investigate and compare the potential effects of peroxisome proliferator-activated receptor (PPAR)-, agonists fenofibrate and n-3 polyunsaturated fatty acids (PUFAs) in modulation of AMPK-,1 activity in liver and skeletal muscle of high-fat diet fed rats. Methods Reverse transcription,polymerase chain reaction was used for determination of AMPK-,1 in liver and soleus muscle and both PPAR-, and CPT-1 in hepatic tissues. Serum, total cholesterol, triacylglycerol, fatty acid and fasting blood glucose were determined colorimetrically. Key findings Both PPAR-, agonists, fenofibrate and n-3 PUFA, increased the mRNA expression of AMPK-,1 activity in liver and skeletal muscle of obese diabetic rats. Fenofibrate was superior in its activation of hepatic mRNA expression of AMPK-, 1 to exert more lipolytic effect and body weight reduction, as estimated through the decrease of triacylglycerol output and serum levels of fatty acid on the one hand and the increase in CPT-1 mRNA expression, the key enzyme in ,-oxidation of fatty acid, on the other hand. n-3 PUFA activated AMPK-,1 mRNA expression in skeletal muscle much more than fenofibrate to reveal more hypoglycaemic effect. Conclusions The PPAR-, agonists fenofibrate and n-3 PUFA could efficiently activate AMPK-,1 mRNA expression in liver and skeletal muscle to exert body weight reduction and hypoglycaemic effect, respectively. [source] Antitumour Activity and Side Effects of Combined Treatment with Chitosan and Cisplatin in Sarcoma 180-Bearing MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000YOSHIYUKI KIMURA We examined the possible modulation by chitosan of the antitumour effects and side effects of cisplatin (cis-diaminedichloroplatinum, CDDP). The study showed that CDDP had potent antitumour activity when administered orally as well as intraperitoneally. We also compared the antitumour activity and side effects of orally administered CDDP plus orally administered chitosan versus intraperitoneally administered CDDP plus orally administered chitosan in sarcoma 180-bearing mice. When CDDP (1.25 mg kg,1 × 2 day,1) was intraperitoneally administered to sarcoma 180-bearing mice, myelotoxicity (the reduction of leucocyte and platelet numbers), nephrotoxicity (the increase of blood nitrogen urea level), immunotoxicity (the reduction of spleen and thymus weight) and a reduction in body weight resulted. These intraperitoneally administered CDDP-induced side effects were not prevented by oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1) for 14 consecutive days. On the other hand, the side effects such as the reductions of body and spleen weights induced by orally administered CDDP (1.25 mg kg,1 × 2 day,1) were prevented by the oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1). From these results, we conclude that the orally administered chitosan plus CDDP might be useful for the prevention of body weight reduction and immunotoxicity (the reduction of spleen weight) induced by the orally administered CDDP without diminishing antitumour activity. [source] Development of the Thyroid Hormone Receptor ,-Subtype Agonist KB-141 : A Strategy for Body Weight Reduction and Lipid Lowering with Minimal Cardiac Side EffectsCARDIOVASCULAR THERAPEUTICS, Issue 2 2005Gary J. Grover ABSTRACT Few treatments for obesity exist and improvements for treatment of hyperlipidemia are still desirable. Thyroid hormone receptors (TRs) regulate body weight, adiposity, and cholesterol levels. However, thyroid hormones can have deleterious effects, particularly cardiac acceleration, that limits the use of hormones in the treatment of obesity. There is evidence that the TR, subtype mediates lowering of blood cholesterol levels and possibly elevation of metabolic rate, whereas TR, appears to control heart rate. In studies, described in this review article, we examined the effects of selective TR, activation on metabolic rate and heart rate in mice, rats and monkeys. T3 had a greater effect on increasing heart rate in wild type (WT) than in TR,-/- mice (ED15 values of 34 and 469 nmol/kg/day, respectively). T3 increased metabolic rate (MVO2) in both WT and TR,-/- mice, but the effect on TR,-/- mice was less pronounced compared to WT mice. Stimulation of MVO2 is mediated by both TR, and TR,, but with different profiles. In cholesterol-fed rats, KB-141, a selective TR, agonist, increased MVO2 with a 10-fold selectivity and lowered cholesterol with a 27-fold selectivity vs. tachycardia. In primates, KB-141 caused significant, cholesterol, Lp(a) and body weight reduction after 1 week of treatment with no effect on heart rate. These data suggest that selective TR, agonists may represent a novel class of drugs for the treatment of obesity, hypercholesterolemia and elevated Lp(a), which may make them useful therapeutics for patients with metabolic syndrome. [source] | ||||||||||