Acute stimulation of leptin concentrations in humans during hyperglycemic hyperinsulinemia. Influence of free fatty acids and fasting.
OBJECTIVE
To assess the acute regulation of leptin concentrations by insulin, glucose and free fatty acids (FFAs).


METHODS
Four protocols: saline control experiment (CON); hyperglycemic clamps (approximately 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).


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


METHODS
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 microM (CON),109+/-15 microM (12 FAST), 484+/-97 microM (36 FAST) and 1762+/-213 microM (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).


CONCLUSIONS
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. International Journal of Obesity (2001) 25, 138-142
Stefan
N
N
Medizinische Klinik, Abteilung für Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universität, Tübingen, Germany.
Fritsche
A
A
Häring
H
H
Stumvoll
M
M
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood*; D007700:Kinetics; D020738:Leptin / Q000097:blood*; D008297:Male; D014280:Triglycerides / Q000096:biosynthesis*
D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D014280:Triglycerides; D006493:Heparin