Open AccessAutotaxin and Its Product Lysophosphatidic Acid Suppress Brown Adipose Differentiation and Promote Diet-Induced Obesity in Mice
Author(s) -
Lorenzo Federico,
Hongmei Ren,
Paul Müeller,
Tao Wu,
Shuying Liu,
Jelena Popović,
Eric M. Blalock,
Manjula Sunkara,
Huib Ovaa,
Harald M. H. G. Albers,
Gordon B. Mills,
Andrew J. Morris,
Susan S. Smyth
Publication year - 2012
Publication title -
molecular endocrinology
Language(s) - English
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2011-1229
Subject(s) - autotaxin , lysophosphatidic acid , biology , adipose tissue , medicine , endocrinology , brown adipose tissue , adipogenesis , white adipose tissue , adipocyte , thermogenesis , thermogenin , microbiology and biotechnology , biochemistry , receptor
Brown adipose tissue is a thermogenic organ that dissipates stored energy as heat to maintain body temperature. This process may also provide protection from development of diet-induced obesity. We report that the bioactive lipid mediator lysophosphatidic acid (LPA) markedly decreases differentiation of cultured primary brown adipocyte precursors, whereas potent selective inhibitors of the LPA-generating enzyme autotaxin (ATX) promote differentiation. Transgenic mice overexpressing ATX exhibit reduced expression of brown adipose tissue-related genes in peripheral white adipose tissue and accumulate significantly more fat than wild-type controls when fed a high-fat diet. Our results indicate that ATX and its product LPA are physiologically relevant negative regulators of brown fat adipogenesis and are consistent with a model in which a decrease in mature peripheral brown adipose tissue results in increased susceptibility to diet-induced obesity in mice.