Abstract
When exposed to cold temperatures, mice increase their thermogenic capacity by an expansion of brown adipose tissue mass and the formation of brite/beige adipocytes in white adipose tissue depots. However, the process of the transcriptional changes underlying the conversion of a phenotypic white to brite/beige adipocytes is only poorly understood. By analyzing transcriptome profiles of inguinal adipocytes during cold exposure and in mouse models with a different propensity to form brite/beige adipocytes, we identified ESRRG and PERM1 as modulators of this process. The production of heat by mitochondrial uncoupled respiration is a key feature of brite/beige compared to white adipocytes and we show here that both candidates are involved in PGC1α transcriptional network to positively regulate mitochondrial capacity. Moreover, we show that an increased expression of ESRRG or PERM1 supports the formation of brown or brite/beige adipocytes in vitro and in vivo. These results reveal that ESRRG and PERM1 are early induced in and important regulators of brite/beige adipocyte formation.
Highlights
White and brown adipose tissue have divergent functions
Even though there is a clear difference in the multilocular adipocyte content (Figure S1B), the transcriptomic changes between 24 h and 7 days of cold exposure were only marginal (Figure 1B), indicating that the transcriptional program for brite/beige adipocyte formation is kept constant after the initial activation
Since estrogen related receptor gamma (ESRRG) and PGC1 and ESRR-induced regulator in muscle 1 (PERM1) can positively regulate brown adipocyte function in vitro, we aimed to investigate whether their overexpression supports browning of white adipose tissue in vivo
Summary
White and brown adipose tissue have divergent functions. White adipocytes store chemical energy within a single lipid droplet to release it back to the body when needed. It is known that brown adipocytes do reside in a distinct fat pad in the interscapular region in rodents, but are found interspersed between white adipocytes in other anatomical locations [3, 4]. The latter have been termed brite (“brown-in-white”) or beige adipocytes and are identified by their multilocular appearance and the expression of UCP1 [5]. Experimental evidence suggests that the arising brite/beige adipocytes can derive from de novo differentiation of stem cells [9, 10] as well as by direct interconversion of mature adipocytes [11,12,13]
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