Endogenous prolactin-releasing peptide regulates food intake in rodents
Yuki Takayanagi, … , Gareth Leng, Tatsushi Onaka
Yuki Takayanagi, … , Gareth Leng, Tatsushi Onaka
Published November 3, 2008
Citation Information: J Clin Invest. 2008;118(12):4014-4024. https://doi.org/10.1172/JCI34682.
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Research Article Metabolism

Endogenous prolactin-releasing peptide regulates food intake in rodents

Abstract

Food intake is regulated by a network of signals that emanate from the gut and the brainstem. The peripheral satiety signal cholecystokinin is released from the gut following food intake and acts on fibers of the vagus nerve, which project to the brainstem and activate neurons that modulate both gastrointestinal function and appetite. In this study, we found that neurons in the nucleus tractus solitarii of the brainstem that express prolactin-releasing peptide (PrRP) are activated rapidly by food ingestion. To further examine the role of this peptide in the control of food intake and energy metabolism, we generated PrRP-deficient mice and found that they displayed late-onset obesity and adiposity, phenotypes that reflected an increase in meal size, hyperphagia, and attenuated responses to the anorexigenic signals cholecystokinin and leptin. Hypothalamic expression of 6 other appetite-regulating peptides remained unchanged in the PrRP-deficient mice. Blockade of endogenous PrRP signaling in WT rats by central injection of PrRP-specific mAb resulted in an increase in food intake, as reflected by an increase in meal size. These data suggest that PrRP relays satiety signals within the brain and that selective disturbance of this system can result in obesity and associated metabolic disorders.

Authors

Yuki Takayanagi, Hirokazu Matsumoto, Masanori Nakata, Takashi Mera, Shoji Fukusumi, Shuji Hinuma, Yoichi Ueta, Toshihiko Yada, Gareth Leng, Tatsushi Onaka

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Figure 5

Role of endogenous PrRP in food intake.

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Changes in BW and food intake after leptin administration. (A) Expressio...
(A and B) Food intake increased the percentage of PrRP neurons expressing p-CREB (A; n = 7 or 9) and the number of Fos-positive PrRP neurons (B; n = 7 or 8) in the rat NTS. Photographs show PrRP neurons (brown cytoplasmic reactions) in the NTS. A dark nuclear reaction indicates p-CREB immunoreactivity. Scale bar: 30 μm. (C) Food intake after a 24-hour fast in WT and PrRP-deficient mice at the age of 14 weeks. Food intake was greater in PrRP-deficient mice (n = 9 or 10). (D) Cumulative food intake of WT and PrRP-deficient mice at the age of 24 weeks. PrRP-deficient mice ate more food (n = 8). (E–H) Cumulative food intake of rats injected i.c.v. with anti-PrRP mAb or mouse IgG at the beginning of the dark period (E and G) or 3 hours after the beginning of the light period (F and H). Rats in G and H were fasted before the i.c.v. injection (n = 8 or 9). (I and J) Meal size but not meal frequency was greater in PrRP-deficient mice (14 weeks old; n = 6 or 10) or rats injected i.c.v. with anti-PrRP mAb (10 weeks old; n = 8) than in control WT mice or control rats. (K) Cumulative food intake of WT mice or PrRP-deficient mice injected i.p. with CCK at the age of 19–21 weeks. Suppression of food intake by CCK was blocked in PrRP-deficient mice (n = 6 or 7). The intake ratio of high-fat diet (L) or tallow (M) was not significantly different in WT and PrRP-deficient mice at the age of 34–37 weeks (n = 4). Error bars indicate SEM. †P < 0.05, ‡P < 0.01, #P < 0.001 versus WT mice; *P < 0.05, ***P < 0.001 versus fasted rats, mouse IgG-injected rats, or vehicle-injected mice. HC, high-carbohydrate diet.