Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

Journal of Pharmacological Sciences

Toshihiko Yada¹  Norihito Shintani²  Shuhei Tomimoto²  Masanori Nakata¹  Kazuya Ikeda²  Akemichi Baba²  Chie Ishida²  Takeshi Shimada²  Tatsuya Ojika²  Hitoshi Hashimoto²  Yusuke Sakurai²  Ken-ichi Hamagami²  Yoshiko Morita² 

[1] Division of Integrative Physiology, Department of Physiology, Jichi Medical University, School of Medicine, Japan;Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan

关键词: adipose tissue;    body weight;    insulin sensitivity;    pituitary adenylate cyclase-activating polypeptide (PACAP);    resistin;   

DOI  :  10.1254/jphs.FP0072173

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(30)Cited-By(25)Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide implicated in several metabolic functions, including insulin secretion and sympathoadrenal activation. To clarify the roles of PACAP in maintenance of whole-body glucose and lipid homeostasis, the impact of the deletion of PACAP on glucose homeostasis, body weight, and adipose tissue mass was examined by comparing mice lacking the Adcyap1 gene encoding PACAP (Adcyap1−/−) with wild-type littermate controls. Adcyap1−/− mice showed significant hypoinsulinemia, although being normoglycemic, and lower body weight as well as reduced food intake. They also showed greatly reduced white adipose tissue mass, in which the mRNA expression of adipocyte fatty acid-binding protein (aP2), a marker of adipocyte differentiation, was decreased. Glucose and insulin tolerance tests revealed increased insulin sensitivity in Adcyap1−/− mice. In accordance with these observations, plasma levels of resistin, an adipocytokine implicated in insulin resistance, were decreased in Adcyap1−/− mice. After a high-fat dietary challenge for six weeks, Adcyap1−/− mice still showed lower body weights and increased insulin sensitivity. These results indicate the crucial roles of PACAP in energy metabolism, including lipid metabolism, and in the regulation of body weight, raising the possibility that the PACAP-signaling pathway that favors energy storage could be a therapeutic target for obesity.

【 授权许可】

Unknown