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Publication : Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis.

First Author  Jiang M Year  2020
Journal  Proc Natl Acad Sci U S A Volume  117
Issue  26 Pages  15055-15065
PubMed ID  32554489 Mgi Jnum  J:295906
Mgi Id  MGI:6438353 Doi  10.1073/pnas.1916550117
Citation  Jiang M, et al. (2020) Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis. Proc Natl Acad Sci U S A 117(26):15055-15065
abstractText  Phosphocholine phosphatase-1 (PHOSPHO1) is a phosphocholine phosphatase that catalyzes the hydrolysis of phosphocholine (PC) to choline. Here we demonstrate that the PHOSPHO1 transcript is highly enriched in mature brown adipose tissue (BAT) and is further induced by cold and isoproterenol treatments of BAT and primary brown adipocytes. In defining the functional relevance of PHOPSPHO1 in BAT thermogenesis and energy metabolism, we show that PHOSPHO1 knockout mice are cold-tolerant, with higher expression of thermogenic genes in BAT, and are protected from high-fat diet-induced obesity and development of insulin resistance. Treatment of mice with the PHOSPHO1 substrate phosphocholine is sufficient to induce cold tolerance, thermogenic gene expression, and allied metabolic benefits. Our results reveal a role of PHOSPHO1 as a negative regulator of BAT thermogenesis, and inhibition of PHOSPHO1 or enhancement of phosphocholine represent innovative approaches to manage the metabolic syndrome.
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