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Acute stimulation of leptin concentrations in humans during hyperglycemic hyperinsulinemia. Influence of free fatty acids and fasting

Abstract

OBJECTIVE: To assess the acute regulation of leptin concentrations by insulin, glucose and free fatty acids (FFAs).

DESIGN: Four protocols: saline control experiment (CON); hyperglycemic clamps (8.3 mmol/l, 120 min) after an overnight fast (12 FAST); after a 36 h fast (36 FAST); and after a 36 h fast during which Intralipid/heparin was given over the last 24 h (36 FAST+FFA).

SUBJECTS: Lean, young, healthy volunteers; control group (n=6), experimental group (n=6).

MEASUREMENTS: Serum leptin concentrations.

RESULTS: Glucose and insulin concentrations were similar during the three clamp protocols. Average FFAs during the last 60 min of the clamp were 671±68 µM (CON),109±15 µM (12 FAST), 484±97 µM (36 FAST) and 1762±213 µM (36 FAST+FFA). Leptin concentrations decreased similarly during 36 FAST and 36 FAST+FFA. Leptin concentrations at 120 min (expressed as percentage of mean basal value) were 0.82±0.02 (CON), 0.93±0.08 (12 FAST) (P=0.29), 1.19±0.06 (36 FAST) (P<0.01) and 1.44±0.12 (36 FAST+FFA) (P<0.01).

CONCLUSION: During a one-day fast leptin concentrations decrease regardless of maintainance of an isocaloric balance. During acute hyperinsulinemic hyperglycemia leptin concentrations increase only after a preceding fast. This increase was most pronounced during simultaneous elevation of FFAs. Overall, our findings are compatible with the hypothesis that leptin secretion may be coupled to triglyceride synthesis rather than to the absolute lipid content of the adipocyte.

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Acknowledgements

We are indebted to Sabine Wolff for her excellent technical help. This study was in part supported by a grant from the Deutsche Forschungsgemeinschaft (DFG), Stu 192-2/1 and by a grant from the European Community (QLRT-1999-00674).

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Stefan, N., Fritsche, A., Häring, H. et al. Acute stimulation of leptin concentrations in humans during hyperglycemic hyperinsulinemia. Influence of free fatty acids and fasting. Int J Obes 25, 138–142 (2001). https://doi.org/10.1038/sj.ijo.0801527

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