Gastroenterology

Gastroenterology

Volume 124, Issue 5, May 2003, Pages 1188-1192
Gastroenterology

Rapid communication
Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats

https://doi.org/10.1016/S0016-5085(03)00281-6Get rights and content

Abstract

Background & Aims:

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.

Section snippets

Materials and methods

Twenty-four, 6-month-old Fischer 344 male rats were purchased from Harlan Italy (San Pietro al Natisone, Italy). All animals were kept in individual cages in the Animal Facility of the University of Trieste in a controlled environment (t = 22°C, 12:12-hour light:dark cycle) and fed a standard commercial chow diet (Harlan 2018, Harlan; 3.4 kcal/g). Experimental protocol and procedures were approved by the Institutional Review Committee for animal studies as part of a larger protocol to study

Results

Leptin infusion reduced overall spontaneous food intake by 26% compared with control rats and super-imposable changes were induced by design in pair-fed animals (Table 1, Figure 1). As expected, leptin-treated and pair-fed rats lost weight moderately but significantly compared with control animals (Table 1). Plasma leptin concentration increased approximately 3-fold in the leptin-treated group and was reduced in the pair-fed group compared with control animals (both P < 0.05 vs. control,

Discussion

The current study demonstrates negative regulation by circulating leptin of plasma ghrelin concentration in vivo. Physiologic increments in plasma leptin prevent a substantial raise in plasma ghrelin concentration observed following 1 week of moderate caloric restriction in lean adult rats. Because ghrelin is an important gastric orexigenic signal in rodents as well as in humans,1, 2, 3, 4 this leptin effect may contribute to sustained reduction of spontaneous food intake during body weight

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The authors thank M. Sturma, A. de Santis, and A. Semolic for skillful technical assistance, and Dr. W. Micheli for invaluable assistance in RIA measurements.

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