307-OR: Delineating the Origin of Supraclavicular Brown Adipocytes

Abstract

Brown adipose tissue (BAT) can use nutrients through non-shivering thermogenesis to generate heat. Thus, activation of BAT can be utilized to maintain body temperature and regulate metabolism. Healthy adult humans possess small amounts of BAT, with the most visible depot, the supraclavicular BAT (scBAT), located in the supraclavicular region of the neck. To understand how human scBAT functions, we previously identified BAT depots in the supraclavicular region of the mouse neck that anatomically resemble human scBAT. Similar to human scBAT, mouse scBAT contains a high density of mitochondria and expresses high levels of uncoupling protein 1. Mouse scBAT first appears in the late fetal stage in the ventral neck and continues to expand toward the lateral neck after birth. To identify the stem/progenitor cells that give rise to supraclavicular brown adipocytes, we performed a series of lineage tracing analyses. Unlike the well-studied mouse interscapular BAT depot, scBAT did not originate from the Myf5, Pax3, or Pax7-labeled progenitor cells that also give rise to skeletal muscle. Rather, a large portion of the supraclavicular brown adipocytes were labeled by Cre recombinase driven by the Mef2c anterior heart field promoter (AHF), which marks cells that give rise to the outflow tract and right ventricle of the heart. Mef2c-AHF+ cells isolated from the scBAT can spontaneously differentiate into highly thermogenic brown adipocytes in vitro, and the differentiation efficiency is further enhanced by addition of Bmp7 and PPARγ agonist, rosiglitazone. Together, our lineage tracing studies revealed that the scBAT is composed of heterogeneous brown adipocyte progenitor cells and that Mef2c-AHF-marked cardiac progenitor cells are one of the ancestors of these brown adipocytes. Understanding the trajectories of and molecular mechanisms by which these progenitor cells give rise to scBAT will provide new insights for developing a novel cell-based therapeutic tool for treating obesity and related metabolic complications. Disclosure Y.Ran: None. Z.Wang: None. M.G.Waterstraat: None. R.Caballero-juarez: None. M.Chen: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116899)