Study of molecular function of A170 as a factor for food intake regulation

点击翻译按钮获取中文摘要

Deficiency of A170, a scaffold protein for aPKC, causes mature-onset obesity in mice, but the mechanisms of the abnormal weight gain are unclear. I found that hyperphagia is the major cause of obesity in A170-deficient (KO) mice. KO and wild-type mice exhibited the same energy expenditure, and food restriction reversed obesity and glucose intolerance in the KO mice. Although their feeding responses to intracerebroventricular administration of an anorexigenic αMSH agonist and the orexigenic peptide NPY were normal, leptin did not induce anorexia, even in young, pre-obese KO mice. Immunohistochemical analyses revealed that A170 was normally expressed in leptin-responsive POMC- or NPY-expressing hypothalamic neurons. Importantly, although the leptin-induced phosphorylation of STAT3 on tyrosine was normal, the translocation of the phosphorylated STAT3 into the nucleus was defective in the KO hypothalamus. We propose that A170 is a novel regulator of leptin's anorectic signaling cascade in the central nervous system.