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Publication : PRADC1: a novel metabolic-responsive secretory protein that modulates physical activity and adiposity.

First Author  Rodriguez S Year  2019
Journal  FASEB J Volume  33
Issue  12 Pages  14748-14759
PubMed ID  31689374 Mgi Jnum  J:286077
Mgi Id  MGI:6391999 Doi  10.1096/fj.201901279R
Citation  Rodriguez S, et al. (2019) PRADC1: a novel metabolic-responsive secretory protein that modulates physical activity and adiposity. FASEB J 33(12):14748-14759
abstractText  Interorgan communication mediated by secreted proteins plays a pivotal role in metabolic homeostasis, yet the function of many circulating secretory proteins remains unknown. Here, we describe the function of protease-associated domain-containing 1 (PRADC1), an enigmatic secretory protein widely expressed in humans and mice. In metabolically active tissues (liver, muscle, fat, heart, and kidney), we showed that Pradc1 expression is significantly suppressed by refeeding and reduced in kidney and brown fat in the context of obesity. PRADC1 is dispensable for whole-body metabolism when mice are fed a low-fat diet. However, in obesity induced by high-fat feeding, PRADC1-deficient female mice have reduced weight gain and adiposity despite similar caloric intake. Decreased fat mass is attributed, in part, to increased metabolic rate, physical activity, and energy expenditure in these animals. Reduced adiposity in PRADC1-deficient mice, however, does not improve systemic glucose and lipid metabolism, insulin sensitivity, liver steatosis, or adipose inflammation. Thus, in PRADC1-deficient animals, decreased fat mass and enhanced physical activity are insufficient to confer a healthy metabolic phenotype in the context of an obesogenic diet. Our results shed light on the physiologic function of PRADC1 and the complex regulation of metabolic health.-Rodriguez, S., Stewart, A. N., Lei, X., Cao, X., Little, H. C., Fong, V., Sarver, D. C., Wong, G. W. PRADC1: a novel metabolic-responsive secretory protein that modulates physical activity and adiposity.
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