1. Membrane Trafficking Protein CDP138 Regulates Fat Browning and Insulin Sensitivity through Controlling Catecholamine Release.
- Author
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Zhou, Qiong L., Ye Song, Chun-Hong Huang, Jun-Yuan Huang, Zhenwei Gong, Zhangping Liao, Sharma, Andria G., Greene, Lily, Deng, Justin Z., Rigor, Michael C., Xiangyang Xie, Songtao Qi, Ayala, Julio E., and Jiang, Zhen Y.
- Subjects
INSULIN resistance ,CATECHOLAMINES regulation ,CALCIUM-binding proteins ,OBESITY ,MAILLARD reaction ,HIGH-fat diet - Abstract
CDP138 is a calcium- and lipid-binding protein that is involved in membrane trafficking. Here, we report that mice without CDP138 develop obesity under normal chow diet (NCD) or high-fat diet (HFD) conditions. CDP138
-1- mice have lower energy expenditure, oxygen consumption, and body temperature than wild-type (WT) mice. CDP138 is exclusively expressed in adrenal medulla and is colocalized with tyrosine hydroxylase (TH), a marker of sympathetic nervous terminals, in the inguinal fat. Compared with WT controls, CDP138-1- mice had altered catecholamine levels in circulation, adrenal gland, and inguinal fat. Adrenergic signaling on cyclic AMP (cAMP) formation and hormone-sensitive lipase (HSL) phosphorylation induced by cold challenge but not by an exogenous β3 adrenoceptor against CL316243 were decreased in adipose tissues of CDP138-1- mice. Cold-induced beige fat browning, fatty acid oxidation, thermogenesis, and related gene expression were reduced in CDP138-1- mice. CDP138-1- mice are also prone to HFD-induced insulin resistance, as assessed by Akt phosphorylation and glucose transport in skeletal muscles. Our data indicate that CDP138 is a regulator of stress response and plays a significant role in adipose tissue browning, energy balance, and insulin sensitivity through regulating catecholamine secretion from the sympathetic nervous terminals and adrenal gland. [ABSTRACT FROM AUTHOR]- Published
- 2018
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