Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytes

Prashant Rajbhandari(University of California, Los Angeles), Douglas Arneson(University of California, Los Angeles), Sydney K. Hart(Institute of Nutrition, Metabolism and Diabetes), In Sook Ahn(University of California, Los Angeles), Graciel Diamante(University of California, Los Angeles), LETÍCIA VITÓRIA DA SILVA SANTOS(Institute of Nutrition, Metabolism and Diabetes), Nima Zaghari(University of California, Los Angeles), An‐Chieh Feng(University of California, Los Angeles), Brandon J. Thomas(University of California, Los Angeles), Laurent Vergnes(University of California, Los Angeles), Stephen D. Lee(University of California, Los Angeles), Abha K. Rajbhandari(Icahn School of Medicine at Mount Sinai), Karen Reue(University of California, Los Angeles), Stephen T. Smale(University of California, Los Angeles), Xia Yang(University of California, Los Angeles), Peter Tontonoz(University of California, Los Angeles)
eLife
October 23, 2019
10.7554/elife.49501
Cited by 177Open Access
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Abstract

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. S ingle N uclei A di p ocyte RNA -seq uencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

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