Acute changes in free-fatty acids (FFA) do not alter serum leptin levels

Abstract

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that little is known about the physiological actions of leptin in humans. The aim of this study was to assess the influence of changes in circulating free-fatty acids on serum leptin levels. Increases in plasma FFA levels (p < 0.02) were obtained in a group of normal subjects following the administration of intralipid plus heparin (250 ml 10% Intralipid plus 5000 U heparin). FFA reduction was achieved through the administration of acipimox (250 mg, orally, at 0 min and at 210 min), a lipid-lowering drug devoid of side effects, to a group of normal (p < 0.02) and obese subjects (p < 0.05). An increase in circulating FFA levels in normal subjects (n = 6), following administration of a lipid-heparin infusion, failed to modify plasma leptin levels as assessed by the area under the curve (AUC; mean +/- SE 892 +/- 168 for placebo vs 896 +/- 260 following intralipid plus heparin). Similarly, whereas acipimox pretreatment induced a reduction in FFA levels compared to placebo in normal (n = 6) and obese subjects (n = 8), it also failed to modify plasma leptin levels at any time-point studied. The results indicate that short-term reduction or increase in circulating FFA are not associated to changes in plasma leptin levels.

Reduction of Plasma Leptin Concentrations by Arginine but Not Lipid Infusion in Humans

“…This in line with two in vivo studies, where changes of plasma FFA induced by acipimox or lipid infusion did not correlate with changes in plasma leptin in normal and abdominally obese subjects (21,22), but contrasts with a recent in vitro study reporting down-regulation of both leptin protein and mRNA by FFA (24). Different composition of plasma FFAs could help to explain the divergent results of the above discussed studies.…”

“…However, the role of FFAs on leptin secretion in animals and humans is not clear at present, because no effect (21)(22)(23), inhibition (24), or even stimulation (25) is reported. Interpretation of some of these results is limited by the increase in insulin secretion typically occurring during lipid infusion (20).…”

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

“…10 Low leptin concentrations could be therefore lead to triglyceride accumulation in pancreatic islets which contributes to b-cell dysfunction 40 as well as to elevation of plasma concentrations of free fatty acids which in turn induce insulin resistance in skeletal muscle. 41 Although shortterm changes in plasma FFA induced by lipid infusion and Acipimox did not affect plasma leptin concentrations, 42 it cannot be ruled out that long-term alterations of lipolysis could modulate leptin secretion.…”

The nicotinic acid analogue acipimox increases plasma leptin and decreases free fatty acids in type 2 diabetic patients

“…In accord with these results, 5 h of lipid infusion resulted in increased leptin mRNA concentrations in subcutaneous fat of healthy volunteers (35). In two other human studies no change in leptin levels was found after a short time (2 or 3 h) of lipid infusion (45,46) or after an additional 3 h of lipid infusion in combination with a hyperglycaemic, hyperinsulinaemic clamp (45). Hennes et al (45) found that acipimox treatment (1750 mg in 8 h) lowered FFA and increased plasma leptin concentrations after a hyperglycaemic, The AUC (plasma concentration´24 h) for glucose, insulin, triglycerides and FFA (mean 6 S.E.)…”