Endogenous prolactin-releasing peptide regulates food intake in rodents
Yuki Takayanagi, Hirokazu Matsumoto, Masanori Nakata, Takashi Mera, Shoji Fukusumi, Shuji Hinuma, Yoichi Ueta, Toshihiko Yada, Gareth Leng, Tatsushi Onaka
Yuki Takayanagi, Hirokazu Matsumoto, Masanori Nakata, Takashi Mera, Shoji Fukusumi, Shuji Hinuma, Yoichi Ueta, Toshihiko Yada, Gareth Leng, Tatsushi Onaka
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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 6

Changes in BW and food intake after leptin administration.

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Role of endogenous PrRP in food intake. (A and B) Food intake increased ...
(A) Expression of p-STAT3 in PrRP neurons following i.c.v. injection of leptin in C57BL/6N mice (11 weeks old). Leptin increased the percentage of PrRP neurons expressing p-STAT3 in the NTS and dorsomedial hypothalamus (DMH) but not in the ventrolateral medulla oblongata (VLM) (n = 4). Photographs show PrRP neurons (brown cytoplasmic reactions) in the DMH. A dark nuclear reaction indicates p-STAT3 immunoreactivity. Scale bar: 30 μm. BW (B) and food intake (C) of WT or PrRP-deficient mice injected i.p. with leptin at the age of 16 weeks. The effects of leptin on BW and food intake were attenuated in PrRP-deficient mice (n = 7). BW (D) and food intake (E) of WT or PrRP-deficient mice injected i.c.v. with leptin at the age of 18–19 weeks. The effects of i.c.v. leptin on BW and food intake were attenuated in PrRP-deficient mice (n = 9–20). Error bars indicate SEM. †P < 0.05, ‡P < 0.01 versus WT mice; *P < 0.05, **P < 0.01 versus vehicle-injected mice.