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Control of fatty acid metabolism by leptin in L6 rat myoblasts is regulated by hyperinsulinemia

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Abstract

The development of hypothalamic leptin resistance plays a role in the development of obesity, yet whether peripheral leptin resistance occurs in obesity and diabetes is controversial. Here we investigate whether hyperinsulinemia, as observed during the development of Type 2 diabetes, modifies the effects of leptin on long chain fatty acid metabolism in skeletal muscle cells. We used boron dipyrromethene difluoride (BODIPY)-labeled palmitate to show that leptin (60 nM) caused a time-dependent (0–60 min) increase in fatty acid uptake in L6 myoblasts. Quantitative analysis using 3H-palmitate showed that pre-incubation with insulin (100 nM, 24 h) prevented stimulation of fatty acid uptake by leptin. Insulin pre-treatment also attenuated the ability of leptin to phosphorylate acetyl Co-A carboxylase and increase palmitate oxidation. Suppressor of cytokine-3 (SOCS-3) has been proposed as a possible mediator of insulin-induced leptin resistance. Here we show that treatment of L6 cells with insulin elicited a time-dependent increase in both SOCS-3 mRNA and protein content. In summary, hyperinsulinemia can induce leptin resistance in L6 myoblasts and this may be mediated via a SOCS-3-dependent mechanism.

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Correspondence to G. Sweeney.

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Eguchi, M., Shrivastava, S., Lyakhovsky, N. et al. Control of fatty acid metabolism by leptin in L6 rat myoblasts is regulated by hyperinsulinemia. J Endocrinol Invest 30, 192–199 (2007). https://doi.org/10.1007/BF03347424

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