Concerted Action of Leptin in Regulation of Fatty Acid Oxidation in Skeletal Muscle and Liver
Central action of leptin on food intake and energy expenditure is integrated with leptin's peripheral action modulating the fatty acid and glucose metabolism and preventing the accumulation of lipids in nonadipose tissues. However, exact mechanism(s) of the leptin's action in the peripheral tissues has not yet been fully elucidated. Therefore, we investigated the effect of a single intravenous injection of leptin on palmitoyl-CoA and palmitoyl-carnitine oxidation rate in liver and skeletal muscle followed by measurements of the carnitine-palmitoyl transferase 1 (CPT1) activity and activities of ss-oxidation enzymes in mitochondria (acyl-CoA dehydrogenase) and in peroxisomes (acyl-CoA oxidase) of rats. Animals were euthanized and tissues and serum harvested 15 min, 1 hour, 3 hours and 6 hours after leptin administration. Intravenous leptin injection increased mitochondrial palmitoyl-CoA oxidation rate in both liver (95%; P<0.025) and skeletal muscle (2.7-fold; P<0.05). This was paralleled by lowering hepatic (-156%; P<0.001) and skeletal muscle (-191%; P<0.001) triglyceride content. Leptin-induced elevation of palmitoyl-CoA oxidation rate in liver was paralleled by increased CPT1 activity (52%; P<0.05) and ss-oxidation capacity (52%; P<0.05). Lack of the leptin's effect on the CPT1-activity in muscle (20%; p=0.09) suggests the existence of an alternative pathway for increasing the palmitoyl-CoA-oxidation rate bypassing the CPT1 regulatory step. Interestingly, leptin stimulated the overall ss-oxidation capacity in muscle by 69% (P=0.027). This may indicate to an involvement of mitochondrial acyl-CoA dehydrogenases as well as of peroxisomal fat catabolism. Taken together, we showed that leptin acutely increases palmitoyl-CoA oxidation rate in liver and in skeletal muscle, which was associated with tissue specific effect on the CPT1 activity as well as on the downstream enzymes of fatty acid oxidation pathways in rat mitochondria and peroxisomes. Tangible evidence for the leptin-induced increase of fatty acid catabolism was provided by a lowered skeletal muscle and hepatic lipid deposition.
Available from: etd.ohiolink.edu
Available from: Karim Chamari
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ABSTRACT: Leptin and adiponectin represent two newly discovered adipose tissue derived hormones; that are both associated with health status and glucose and free fatty acid (FFA) metabolism. Moreover, acute and chronic exercises affect body composition, carbohydrate and lipid metabolism. It is thus interesting to evaluate the effects of physical exercise and training on leptin and adiponectin levels. It seems that leptin concentration is not modified after short-term exercise (<60 min) or exercise that generates an energy expenditure lower than 800 kcal. Leptin levels decrease after long-term exercise (> or =60 min) stimulating FFA release, or after exercise that generates energy expenditure higher than 800 kcal. Adiponectin concentration presents a delayed increase (30 min) after short-term intense exercise (<60 min) performed by trained athletes. For adiponectin, limited data suggest that adiponectin concentration presents a delayed increase (30 min) after short-term intense exercise (<60 min) performed by trained athletes. It seems that adiponectin concentrations do not change in response to long-term exercise (> or =60 min). Short-term training (<12 weeks) and long-term training (> or =12 weeks) show contrasting results regarding leptin and adiponectin. Most training studies which improve fitness levels and affect body composition could decrease leptin and increase adiponectin concentrations.
Available from: Khan Hekmatyar
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ABSTRACT: Leptin is known to be associated with regulation of body weight and fat content. The effects of exogenous leptin on abdominal visceral (VS) and subcutaneous (SC) fat volume and hepatic fat-to-water ratio in leptin-deficient obese mice were investigated by (1)H magnetic resonance imaging (MRI). Chemical shift-selected fat and water (1)H MRI of control and leptin-treated mice were obtained 1 day before treatment and after 7 days of treatment (0.3 mg/kg/day). Hepatic fat-to-water ratio and VS fat volume decreased significantly with treatment, whereas SC fat volume did not change. Noninvasive measurement of fat and water content in different body regions using MRI should prove useful for evaluating new drugs for the treatment of obesity and other metabolic disorders.
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