Regulation of leptin secretion from white adipocytes by free fatty acids.
Norepinephrine stimulates lipolysis and concurrently inhibits insulin-stimulated leptin secretion from white adipocytes. To assess whether there is a cause-effect relationship between these two metabolic events, the effects of fatty acids were investigated in isolated rat adipocytes incubated in buffer containing low (0.1%) and high (4%) albumin concentrations. Palmitic acid (1 mM) mimicked the inhibitory effects of norepinephrine (1 microM) on insulin (10 nM)-stimulated leptin secretion, but only at low albumin concentrations. Studies investigating the effects of the chain length of saturated fatty acids [from butyric (C4) to stearic (C18) acids] revealed that only fatty acids with a chain length superior or equal to eight carbons effectively inhibited insulin-stimulated leptin secretion. Long-chain mono- and polyunsaturated fatty acids constitutively present in adipocyte triglyceride stores (oleic, linoleic, gamma-linolenic, palmitoleic, eicosapentanoic, and docosahexanoic acids) also completely suppressed leptin secretion. Saturated and unsaturated fatty acids inhibited insulin-stimulated leptin secretion with the same potency and without any significant effect on basal secretion. On the other hand, inhibitors of mitochondrial fatty acid oxidation (palmoxirate, 2-bromopalmitate, 2-bromocaproate) attenuated the stimulatory effects of insulin on leptin release without reversing the effects of fatty acids or norepinephrine, suggesting that fatty acids do not need to be oxidized by the mitochondria to inhibit leptin release. These results demonstrate that long-chain fatty acids mimic the effects of norepinephrine on leptin secretion and suggest that they may play a regulatory role as messengers between stimulation of lipolysis by norepinephrine and inhibition of leptin secretion.
Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Quebec, Canada G1K 7P4.
Philippe G
PG
Cammisotto
Yves
Y
Gélinas
Yves
Y
Deshaies
Ludwik J
LJ
Bukowiecki
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013566:Sympathomimetics / Q000494:pharmacology
D000418:Albumins; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D013566:Sympathomimetics; D019308:Palmitic Acid; D009638:Norepinephrine