Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation

  1. Jiandie D. Lin1,2,*
  1. 1Life Sciences Institute
  2. 2Department of Cell & Developmental Biology
  3. 3Department of Internal Medicine
  4. 4Department of Molecular & Integrative Physiology
  5. 5Department of Pediatrics and Communicable Diseases; University of Michigan Medical School, Ann Arbor, MI 48109
  6. 6Weldon School of Biomedical Engineering and Department of Chemistry, Purdue University, West Lafayette, IN 47907
  1. *Corresponding Author: Jiandie Lin, Email: jdlin{at}


Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism in part through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated. Here we identified Otopetrin 1 (Otop1) as a component of a counter-inflammatory pathway that is induced in WAT during obesity. Otop1 expression is markedly increased in obese mouse WAT and is stimulated by TNFα in cultured adipocytes. Otop1 mutant mice respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation. Otop1 attenuates interferon γ (IFNγ) signaling in adipocytes through selective downregulation of the transcription factor STAT1. Using a tagged vector, we found that Otop1 physically interacts with endogenous STAT1. Thus, Otop1 defines a unique target of cytokine signaling that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity.

  • Received July 23, 2013.
  • Accepted December 19, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.