Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats.
OBJECTIVE
Ghrelin is an orexigenic hormone secreted by the stomach. Increased plasma ghrelin concentration was reported during diet-induced weight loss in obese humans, suggesting that ghrelin contributes to adaptive increment in appetite associated with caloric restriction. Leptin reduces spontaneous food intake and body weight in rodents. The current study tested the hypothesis that increased plasma leptin prevents the potential increase in plasma ghrelin concentration during moderate caloric restriction in lean rats.


METHODS
Six-month-old male rats (body weight, 367 +/- 9 grams) were randomly assigned to one of the following treatments (8 rats each) for 1 week: (1) leptin subcutaneous infusion to induce moderate hyperleptinemia and moderate caloric restriction (-26% of ad libitum), (2) vehicle infusion and pair feeding, and (3) vehicle infusion and ad libitum feeding.


RESULTS
Leptin-treated (-19 +/- 5 grams) and pair-fed (-19 +/- 2) rats lost weight compared with ad libitum-fed rats (-3 +/- 1, P < 0.05). Compared with control (6.8 +/- 0.7 ng/mL), plasma leptin was higher in leptin-treated (18.6 +/- 0.9 ng/mL, P < 0.01) rats and lower in pair-fed rats (4.3 +/- 0.4 ng/mL, P < 0.05). Plasma ghrelin was substantially higher in calorie-restricted than control rats (2505 +/- 132 pg/mL vs. 1790 +/- 134 pg/mL, P < 0.01), and leptin treatment (1625 +/- 117 pg/mL) completely prevented this change. Plasma ghrelin concentration was negatively correlated with body weight changes in calorie-restricted and control (r = -0.75, P < 0.01) but not in leptin-treated rats (P > 0.8).


CONCLUSIONS
Moderate hyperleptinemia prevents an increase of plasma ghrelin during moderate short-term caloric restriction. Satiety-inducing effects of leptin include suppression of gastric orexigenic signals and disruption of a potential feedback mechanism between body weight changes and plasma ghrelin in lean adult rats.
Barazzoni
Rocco
R
Dipartmento di Scienze Cliniche, Morfologiche e Technologiche-DSCMT, Clinica Medica, Trieste, Italy. barazzon@units.it
Zanetti
Michela
M
Stebel
Marco
M
Biolo
Gianni
G
Cattin
Luigi
L
Guarnieri
Gianfranco
G
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D004435:Eating / Q000187:drug effects; D025461:Feedback, Physiological / Q000187:drug effects; D054439:Ghrelin; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D008297:Male; D036361:Peptide Hormones / Q000097:blood*; D051381:Rats; D011916:Rats, Inbred F344; D012527:Satiation / Q000187:drug effects
D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones