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. Single Nuclei Adipocyte RNA-sequencing (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.
Highlights
Adipose tissue plays an important role in the maintenance of energy balance in mammals
We showed that chromatin accessibility at thermogenic genes in subcutaneous adipose tissue was linked to IL10 signaling; whether adipocytes themselves are the primary target for the metabolic effects of IL10 in vivo remains to be established
We previously reported that global IL10-deficient mice have increased energy expenditure and browning of white adipose tissue (Rajbhandari et al, 2018)
Summary
Adipose tissue plays an important role in the maintenance of energy balance in mammals. A chronic imbalance between energy intake and expenditure increases adiposity and leads to obesity and predisposes to the development of metabolic disease (Rosen and Spiegelman, 2014; Wajchenberg, 2000). White adipose tissue (WAT) is essential for triglyceride (TG) storage, whereas thermogenic brown adipose tissue (BAT) dissipates energy as heat through mitochondrial uncoupling mechanisms including uncoupling protein 1 (UCP1) Increasing the activity of thermogenic adipocytes in animal models counteracts the development of obesity and diabetes (Cohen et al, 2014; Harms and Seale, 2013; Song et al, 2016; Villanueva et al, 2013). A better understanding of the mechanisms controlling adipose thermogenesis could inform the development of new therapies for metabolic diseases
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