1. Membrane Trafficking Protein CDP138 Regulates Fat Browning and Insulin Sensitivity through Controlling Catecholamine Release.
- Author
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Zhou QL, Song Y, Huang CH, Huang JY, Gong Z, Liao Z, Sharma AG, Greene L, Deng JZ, Rigor MC, Xie X, Qi S, Ayala JE, and Jiang ZY
- Subjects
- Adrenal Glands metabolism, Animals, Cell Membrane metabolism, Diet, High-Fat adverse effects, Energy Metabolism physiology, Gene Expression physiology, Lipid Metabolism physiology, Mice, Mice, Inbred C57BL, Muscle, Skeletal metabolism, Phosphorylation physiology, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction physiology, Sterol Esterase metabolism, Thermogenesis physiology, Adipose Tissue, Brown metabolism, Catecholamines metabolism, Homeodomain Proteins metabolism, Insulin Resistance physiology, Membrane Proteins metabolism, Protein Transport physiology
- 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
-/- 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-/- 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-/- mice. Cold-induced beige fat browning, fatty acid oxidation, thermogenesis, and related gene expression were reduced in CDP138-/- mice. CDP138-/- 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., (Copyright © 2018 American Society for Microbiology.)- Published
- 2018
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