Senescent T Cell Induces Brown Adipose Tissue "Whitening" Via Secreting IFN-γ.

Xiao-Xi Pan,Ping-Jin Gao,Run Zhang,Kang-Li Yao,Qian Ge,Fang Wu,Yong-Feng Yang,Cheng-Chao Ruan

doi:10.3389/fcell.2021.637424

Abstract

Aging-associated chronic inflammation is a key contributing factor to a cluster of chronic metabolic disorders, such as cardiovascular disease, obesity, and type 2 diabetes. Immune cells particularly T cells accumulate in adipose tissue with advancing age, and there exists a cross talk between T cell and preadipocyte, contributing to age-related adipose tissue remodeling. Here, we compared the difference in morphology and function of adipose tissue between young (3-month-old) and old (18-month-old) mice and showed the phenomenon of brown adipose tissue (BAT) “whitening” in old mice. Flow cytometry analysis suggested an increased proportion of T cells in BAT of old mice comparing with the young and exhibited senescent characteristics. We take advantage of coculture system to demonstrate directly that senescent T cells inhibited brown adipocyte differentiation of preadipocytes in adipose tissue. Mechanistically, both in vitro and in vivo studies suggested that senescent T cells produced and released a higher level of IFN-γ, which plays a critical role in inhibition of preadipocyte-to-brown adipocyte differentiation. Taken together, the data indicate that senescent T cell-derived IFN-γ is a key regulator in brown adipocyte differentiation.

Highlights

Advancing age is a major risk factor for chronic metabolic diseases, including cardiovascular disease and type 2 diabetes (Partridge et al, 2018)
UCP1 was weakly detected in the subcutaneous adipose tissue (SAT) of young mice, whereas it was not detected in old mice (Figure 1C)
Western blot and qRT-PCR analysis demonstrated that a lower level of UCP-1 both in brown adipose tissue (BAT) of old mice than that in young mice (Figures 1D,E). qRT-PCR analysis further indicated that genes involved in brown adipocyte formation, such as Pparg and

Summary

Introduction

Advancing age is a major risk factor for chronic metabolic diseases, including cardiovascular disease and type 2 diabetes (Partridge et al, 2018). It has become evident that adipose tissue plays an endocrine function, not merely an energy reservoir pool, and exerts a fundamental influence on metabolic regulation (Oikonomou and Antoniades, 2019; Scheja and Heeren, 2019). Adipose tissue is classified as white adipose tissue (WAT) and brown adipose tissue (BAT). BAT has been considered a key for thermogenesis to maintaining body temperature, while WAT stores and releases lipids and is involved in promoting inflammation (Bartelt and Heeren, 2014; van Eenige et al, 2018). Extensive studies have indicated that WAT could obtain multilocular lipid droplet morphology and expression of BAT-specific genes such as Ucp, Pparg, and Pgc1a in response to various stimuli (Harms and Seale, 2013). BAT “whitening” refers to acquisition of white adipocyte characteristics with enlarged lipid droplets and loss of normal

Methods

Results

Conclusion