CD8+ T cells in beige adipogenesis and energy homeostasis

Abstract

Although accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance, it remains unclear whether lymphocytes also participate in the regulation of energy homeostasis in the WAT. Here, we demonstrate enhanced energy dissipation in Rag1-/- mice, increased catecholaminergic input to subcutaneous WAT, and significant beige adipogenesis. Adoptive transfer experiments demonstrated that CD8+ T cell deficiency accounts for the enhanced beige adipogenesis in Rag1-/- mice. Consistently, we identified that CD8-/- mice also presented with enhanced beige adipogenesis. The inhibitory effect of CD8+ T cells on beige adipogenesis was reversed by blockade of IFN-γ. All together, our findings identify an effect of CD8+ T cells in regulating energy dissipation in lean WAT, mediated by IFN-γ modulation of the abundance of resident immune cells and of local catecholaminergic activity. Our results provide a plausible explanation for the clinical signs of metabolic dysfunction in diseases characterized by altered CD8+ T cell abundance and suggest targeting of CD8+ T cells as a promising therapeutic approach for obesity and other diseases with altered energy homeostasis.

Eosinophil function in adipose tissue is regulated by Krüppel-like factor 3 (KLF3)

“…7g). Unexpectedly, we detected increased expression of Ifng (encoding the inflammatory cytokine interferon-γ) in Klf3 −/− , which has been shown to block themogenesis 50 . On the other hand, levels of Il10 were reduced in the absence of KLF3, in line with recent findings that IL-10 blockade protects against diet-induced obesity and elicits browning of AT 51 .…”

Regulation, Communication, and Functional Roles of Adipose Tissue-Resident CD4+ T Cells in the Control of Metabolic Homeostasis

“…Rag1 −/− mice that lack both T and B lymphocytes display excess weight gain under HFD-feeding conditions, which is at least in part due to decreased energy expenditure resulted from decreased UCP-1 expression in BAT ( 85 ). In contrast, another study showed that even in the lean state, Rag1 −/− mice display more energy expenditure and upregulated of UCP1 expression in SAT than WT mice at room temperature ( 86 ). Decreased CD8 + T cells, but not CD4 + T cells, are believed to contribute to promote beige fat development, mainly due to the decreased IFN-γ secretion ( 86 ).…”

“…In contrast, another study showed that even in the lean state, Rag1 −/− mice display more energy expenditure and upregulated of UCP1 expression in SAT than WT mice at room temperature ( 86 ). Decreased CD8 + T cells, but not CD4 + T cells, are believed to contribute to promote beige fat development, mainly due to the decreased IFN-γ secretion ( 86 ). However, given that Th1 cells are also major producers of IFN-γ and that HFD feeding increases both the percentage and the total number of Th1 cells in SAT, it is possible that Th1 cells may also be involved in the regulation of energy expenditure.…”

T Cells in Adipose Tissue in Aging

“…Beige adipocytes, which may develop within white adipose depots, particularly in subcutaneous adipose depots, have a similar energy dissipation function as that of brown adipocytes, which is mainly induced by cold and beta-adrenergic activation (74–76). Innate and adaptive immune system components are reported to contribute to and regulate the energy storage/dissipation functions of adipose tissue (77–79). Recent reports suggest that along with macrophages, T cells may play a significant role in the regulation and maintenance of thermogenesis and overall adipose tissue energy homeostasis.…”