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 2

Late-onset obesity in PrRP-deficient mice.

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Late-onset obesity in PrRP-deficient mice. (A) Mean BWs of WT, PrRP-hete...
(A) Mean BWs of WT, PrRP-heterozygous, and PrRP-deficient mice from heterozygous intercrosses, fed a high-fat diet (HF) from the age of 5 weeks. Under the high-fat diet condition, PrRP-deficient mice became heavier than WT and PrRP-heterozygous mice from the age of 7 weeks (n = 6 or 7). Mean BWs (B) and cumulative food intake (C) of WT and PrRP-deficient mice at the ages of 6–72 weeks. PrRP-deficient mice older than 18 weeks were heavier and ate more than WT mice (n = 6). (D) At 66 weeks of age, PrRP-deficient mice were markedly fatter than WT mice. Scale bar: 5 cm. (E) At the age of 39–40 weeks, PrRP-deficient mice fed standard laboratory chow showed reduced glucose tolerance compared with WT mice (n = 5 or 6). (F) Insulin resistance tests at the age of 40–41 weeks showed that PrRP-deficient mice also had increased insulin resistance. (Blood glucose concentrations before insulin administration were set as 100%; n = 5 or 6.) (G) Mean weight of fat pads of subcutaneous region (Sub), perirenal region (Peri), mesenteric region (Mes), epididymal region (Epi), and BAT. At the age of 72 weeks, PrRP-deficient mice had much larger fat masses than WT mice (n = 6). (H) WAT (upper panel) and liver (lower panel) of WT and PrRP-deficient mice at the age of 72 weeks (H&E staining). Scale bars: 100 μm. Error bars indicate SEM. †P < 0.05, ‡P < 0.01, #P < 0.001 versus WT mice; *P < 0.05 versus PrRP-heterozygous mice.