Control of fatty acid metabolism by leptin in L6 rat myoblasts is regulated by hyperinsulinemia.
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.
Eguchi
M
M
Department of Biology, York University, Toronto, Ontario, Canada.
Shrivastava
S
S
Lyakhovsky
N
N
Kim
W
W
Palanivel
R
R
Sweeney
G
G
D000818:Animals; D002460:Cell Line; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology
D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins