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Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/28/2003 Publication Date: 1/23/2004 Citation: Ramsay, T.G. 2004. Porcine leptin alters isolated adipocyte glucose and fatty acid metabolism. Domestic Animal Endocrinology. 26:11-21. Interpretive Summary: Leptin is a hormone produced by adipose tissue that can affect feeding behavior, animal health and reproduction. Studies in pigs have demonstrated that leptin can reduce feed intake when injected directly to the brain. Leptin administration has been shown to alter peripheral metabolism and reduce the fat mass in rodents, although peripheral effects in the pig are unknown. This study demonstrated that leptin treatment can alter fatty acid metabolism by pig fat cells, with little effect on carbohydrate metabolism. These metabolic effects are a direct response to leptin. This immediate response suggests that synthesis and secretion of additional autocrine/paracrine factors are not necessary prior to changes in fatty acid metabolism, while an effect on glucose metabolism requires additional factors. The ability for leptin to inhibit palmitate usage by adipocytes for lipid synthesis suggests that leptin can function to partition energy away from adipose tissue. Further research into this partitioning effect of leptin may contribute to production of leaner animals at the expense of fat production. Technical Abstract: This study examined if leptin can acutely affect glucose or fatty acid metabolism in pig adipocytes and whether leptin's actions on lipogenesis are manifested through interaction with insulin or growth hormone. Subcutaneous adipose tissue was obtained from ~55 kg crossbred barrows at an abattoir. Isolated adipocytes were prepared using a collagenase procedure. Experiments assessed U-14C-glucose or 1-14C-palmitate metabolism in isolated adipocytes exposed to: basal medium (control), 100 nM insulin, 100 ng/mL porcine growth hormone, 100 ng/mL recombinant porcine leptin, and combinations of these hormones. Treatments were performed in triplicate and the experiment was repeated with adipocytes isolated from five different animals. Cell aliquots (250 mL) were added to 1 mL of incubation medium, then incubated for two hours at 37° C for measurement of glucose and palmitate oxidation or incorporation into lipid. Incubation of isolated adipocytes with insulin increased glucose oxidation rate by 18% (P<0.05), while neither growth hormone nor leptin affected glucose oxidation (P>0.5). Total lipid synthesis from glucose was increased by approximately 25% by 100 nM insulin or insulin + growth hormone (P<0.05). Insulin + leptin reduced the insulin response by 37% (P<0.05). The combination of all three hormones increased total lipid synthesis by 35%, relative to controls (P<0.05), a rate similar to insulin alone. Fatty acid synthesis was elevated by insulin (32%, P<0.05) or growth hormone (13%, P<0.05). Leptin had no effect on fatty acid synthesis (P>0.05). Leptin reduced the esterification rate by 10% (P<0.05). Growth hormone and insulin could overcome leptin's inhibition of palmitate esterification (P>0.05). |
