TY - JOUR
T1 - FADD regulates adipose inflammation, adipogenesis, and adipocyte survival
AU - Tang, Jianlei
AU - Ma, Yue
AU - Li, Meilin
AU - Liu, Xiangpeng
AU - Wang, Yuting
AU - Zhang, Jie
AU - Shu, Hui
AU - Liu, Zhiwei
AU - Zhang, Chi
AU - Fu, Lei
AU - Hu, Ji
AU - Zhang, Yong
AU - Jia, Zhihao
AU - Feng, Yu
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.
AB - Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.
UR - http://www.scopus.com/inward/record.url?scp=85198340072&partnerID=8YFLogxK
U2 - 10.1038/s41420-024-02089-x
DO - 10.1038/s41420-024-02089-x
M3 - Article
AN - SCOPUS:85198340072
SN - 2058-7716
VL - 10
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 323
ER -
