| Title | FAM96A is essential for maintaining organismal energy balance and adipose tissue homeostasis in mice |
| Authors | Liu, Zhuanzhuan Xu, Shihong Zhang, Zhiwei Wang, Hanying Jing, Qiyue Zhang, Shenghan Liu, Mengnan Han, Jinzhi Kou, Yanbo Wei, Yanxia Wang, Lu Wang, Yugang |
| Affiliation | Xuzhou Med Univ, Dept Pathogen Biol & Immunol, Jiangsu Key Lab Immun & Metab, Xuzhou, Jiangsu, Peoples R China Peking Univ, Ctr Human Dis Genom, Beijing, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Immunol, Beijing, Peoples R China Peking Univ, NHC Key Lab Med Immunol, Beijing, Peoples R China Xuzhou Med Univ, Dept Pathogen Biol & Immunol, Tongshan Rd 209, Xuzhou 221004, Jiangsu, Peoples R China |
| Keywords | MEASURING REACTIVE OXYGEN IRON-SULFUR PROTEINS MAMMALIAN TARGET COORDINATES IRON BIOGENESIS PHOSPHOFRUCTOKINASE DEFICIENCY METABOLISM CLUSTER CITRATE |
| Issue Date | 1-Nov-2022 |
| Publisher | FREE RADICAL BIOLOGY AND MEDICINE |
| Abstract | The iron (Fe) metabolism plays important role in regulating systemic metabolism and obesity development. The Fe inside cells can form iron-sulfur (Fe-S) clusters, which are usually assembled into target proteins with the help of a conserved cluster assembly machinery. Family with sequence similarity 96A (FAM96A; also designated CIAO2A) is a cytosolic Fe-S assembly protein involved in the regulation of cellular Fe homeostasis. However, the biological function of FAM96A in vivo is still incompletely defined. Here, we tested the role of FAM96A in regulating organismal Fe metabolism, which is relevant to obesity and adipose tissue homeostasis. We found that in mice genetically lacking FAM96A globally, intracellular Fe homeostasis was interrupted in both white and brown adipocytes, but the systemic Fe level was normal. FAM96A deficiency led to adipocyte hypertrophy and organismal energy expenditure reduction even under nonobesogenic normal chow diet-fed conditions. Mecha-nistically, FAM96A deficiency promoted mechanistic target of rapamycin (mTOR) signaling in adipocytes, leading to an elevation of de novo lipogenesis and, therefore, fat mass accumulation. Furthermore, it also caused mitochondrial defects, including defects in mitochondrial number, ultrastructure, redox activity, and metabolic function in brown adipocytes, which are known to be critical for the control of energy balance. Moreover, adipocyte-selective FAM96A knockout partially phenocopied global FAM96A deficiency with adipocyte hyper-trophy and organismal energy expenditure defects but the mice were resistant to high-fat diet-induced weight gain. Thus, FAM96A in adipocytes may autonomously act as a critical gatekeeper of organismal energy balance by coupling Fe metabolism to adipose tissue homeostasis. |
| URI | http://hdl.handle.net/20.500.11897/657297 |
| ISSN | 0891-5849 |
| DOI | 10.1016/j.freeradbiomed.2022.09.011 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 |
