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

Susana Rodriguez, Ashley N. Stewart, Xia Lei, Xi Cao, Hannah C. Little, Vincent Fong, Dylan C. Sarver, G. William Wong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14748-14759
Number of pages12
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number12
DOIs
StatePublished - Dec 1 2019

    Fingerprint

Keywords

  • diabetes
  • insulin resistance
  • lipid metabolism
  • obesity

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this