No abstract

The present study sought to identify gene networks that are hallmarks of the developing inguinal subcutaneous adipose tissue (iWAT) and the interscapular brown adipose tissue (BAT) in the mouse. RNA profiling revealed that the iWAT of postnatal (P) day 6 mice expressed thermogenic and lipid catabolism transcripts, along with the abundance of transcripts associated with the beige adipogenesis program. This was an unexpected finding, as thermogenic BAT was believed to be the only site of nonshivering thermogenesis in the young mouse. However, the transcriptional landscape of BAT in P6 mice suggests that it is still undergoing differentiation and maturation, and that the iWAT temporally adopts thermogenic and lipolytic potential. Moreover, P6 iWAT and adult (P56) BAT were similar in their expression of immune gene networks, but P6 iWAT was unique in the abundant expression of antimicrobial proteins and virus entry factors, including a possible receptor for SARS-CoV-2. In summary, postnatal iWAT development is associated with a metabolic shift from thermogenesis and lipolysis towards fat storage. However, transcripts of beige-inducing signal pathways including β-adrenergic receptors and interleukin-4 signaling were underrepresented in young iWAT, suggesting that the signals for thermogenic fat differentiation may be different in early postnatal life and in adulthood.

No abstract

Infant nutrition is rich in lipids, and the adipose tissue has been adapted to properly break down neutral lipids and oxidize fatty acids in infancy. Accordingly, infant adipose tissue contains so-called beige adipocytes, which burn off lipids to heat, and impede fat storage and obesity. We show here that infant adipocytes are immune privileged sites for mitochondria due to a blockade in interferon regulatory factor 7 (IRF7)-signaling, which allows mitochondrial RNA to trigger beige adipocyte differentiation through mitochondria-to-nucleus signaling. These mechanisms serve to maintain an extensive mitochondrial network in beige adipocytes and protect against obesity. By contrast, fat storing white adipocytes lack these mechanisms and respond to their mitochondrial content with inflammation. We show that obesity subverts the immune privilege for mitochondria in adipocytes, which reduces mitochondrial mass and abrogates beige adipocyte development. In turn, suppressing IRF7 signaling and restoring the RNA-mediated mitochondria-to-nucleus signaling in adipocytes effectively reduces obesity.