Brown adipose tissue (BAT) is a thermogenic organ that promotes metabolic fitness. In humans, there are two spatiotemporally distinct phases of BAT ontogeny: the prenatally developed dorsal-anterior-located interscapular and retroperitoneal BAT; and the postnatally emerged anterior cervical and supraclavicular BAT. It has been established in rodents that the dorsal-anterior-located BAT depots predominately arise from a Pax3+/Myf5+ lineage in the epaxial dermomyotome that also forms the trunk muscle. However, the developmental origins of the anterior cervical and supraclavicular BAT that adult humans have remain unknown. In this study, using lineage tracing mouse models, we found that these neck BAT depots are not derived from the Pax3+ or Myf5+ precursor cells. Knock out of PPARγ, the master regulator of adipogenesis, in Myf5+ cells caused severe atrophy of interscapular BAT, but did not affect the anterior cervical and supraclavicular depots. Instead, we identified that roughly half of the anterior cervical and supraclavicular brown adipocytes are progeny cells of a developmental lineage that also gives rise to neck muscle cells. PPARγ deficiency in this lineage did not perturb iBAT development, but caused paucity in the anterior cervical and supraclavicular regions, thus sensitizing mice to cold-induced decrease in body temperature.
In summary, our results suggest that there are region-specific myogenic precursors that contribute to BAT development at different anatomical locations. Future studies to understand the pathophysiological regulation of these developmentally distinct BAT depots could inspire new approaches to measure BAT mass and to activate BAT activity in humans for the treatment of obesity, diabetes and related metabolic disorders.
H.Ruan: None. Z.Zhang: None. Z.Huang: None.
American Diabetes Association (1-18-IBS-167)