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Leptin is reported to have effects in peripheral tissues that are independent of its central effects on food intake and body weight. In this study, the acute effects of a single dose of recombinant mouse leptin on lipid and glucose metabolism in lean and gold thioglucose-injected obese mice were examined. Changes were measured 2 h after leptin injection. In lean mice, liver and white adipose tissue (WAT) lipogenesis was inhibited. The activity of the pyruvate dehydrogenase complex (PDHCa), the rate-determining step for glucose oxidation, was reduced in heart, liver, quadriceps muscle, and both brown and white adipose tissues. Muscle and liver glycogen and liver triglyceride (TG) content was unchanged, but muscle TG was decreased. In obese mice, liver and WAT lipogenesis was inhibited and PDHCa reduced in heart and quadriceps muscle. Muscle and liver glycogen was decreased but not TG. Serum insulin was reduced in obese but not lean mice. These results are consistent with a role for leptin in the maintenance of steady-state energy stores by decreasing lipid synthesis and increasing fat mobilization, with decreased glucose oxidation occurring as a result of increased fatty acid oxidation.

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MALONEY, CHRIS A., ALISON K. GOSBY, JENNY L. PHUYAL, GARETH S. DENYER, JANET M. BRYSON, AND IAN D. CATERSON. Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed to a low-protein diet in utero. Obes Res. 2003;11:461-468. Objective: Intrauterine growth restriction is associated with increased prevalence of the metabolic syndrome in adult life, including increased adiposity. The aim of this study was to investigate if maternal protein energy malnutrition is associated with changes in expression of genes involved in fat partitioning in weanling rats. Research Methods and Procedures: Time-mated mothers were placed on one of two isocaloric diets, low protein [(LP), 8% protein] or control (20% protein). All mothers remained on the diet throughout pregnancy and lactation. A third group received control for 2 weeks and was switched to LP for the last week of pregnancy and lactation [late low protein (LLP) group]. Offspring were analyzed at weaning for serum glucose, nonesterified fatty acids, triglyceride, and insulin. Expression of the genes acetyl-coenzyme A carboxylase, fatty acid synthase, and carnitine palmitoyl transferase 1 were measured in liver, quadriceps muscle, and subcutaneous white adipose tissue using semiquantitative reverse transcription-polymerase chain reaction. Results: LLP and LP offspring were shorter, weighed less, had reduced serum insulin and nonesterified fatty acids, and had increased serum glucose, serum triglycerides, and hepatic triglycerides. Hepatic gene expression of acetyl-coenzyme A carboxylase and fatty acid synthase was increased 2-fold in LLP and LP offspring (p Ͻ 0.001). These changes were not seen in muscle or subcutaneous white adipose tissue. CPT-1 gene expression was unaltered in all tissues examined. Discussion: Maternal protein energy malnutrition programs gene expression of lipogenic enzymes in the liver of weanling offspring in a manner favoring fat synthesis that may predispose these offspring to fat accumulation and insulin resistance later in life.