Extended lifespan and reduced adiposity in mice lacking the FAT10 gene

Abstract

The HLA-F adjacent transcript 10 (FAT10) is a member of the ubiquitinlike gene family that alters protein function/stability through covalent ligation. Although FAT10 is induced by inflammatory mediators and implicated in immunity, the physiological functions of FAT10 are poorly defined. We report the discovery that FAT10 regulates lifespan through pleiotropic actions on metabolism and inflammation. Median and overall lifespan are increased 20% in FAT10ko mice, coincident with elevated metabolic rate, preferential use of fat as fuel, and dramatically reduced adiposity. This phenotype is associated with metabolic reprogramming of skeletal muscle (i.e., increased AMP kinase activity, β-oxidation and -uncoupling, and decreased triglyceride content). Moreover, knockout mice have reduced circulating glucose and insulin levels and enhanced insulin sensitivity in metabolic tissues, consistent with elevated IL-10 in skeletal muscle and serum. These observations suggest novel roles of FAT10 in immune metabolic regulation that impact aging and chronic disease.longevity | obesity | mammals

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

“…4c,d), Interestingly, disruption of Ubd in mice has been shown to improve glucose tolerance along with other metabolic parameters but the impact on gut microbiota has not been examined46. Thus, while we have shown that Irgm1 is a mediator of the effect of IFNγ on A. muciniphila, it is plausible that other IFNγ-dependent mechanisms may also contribute to this phenomenon.…”

Knockdown of ubiquitin D inhibits adipogenesis during the differentiation of porcine intramuscular and subcutaneous preadipocytes

“…Systemic UBD‐deficient mice showed hypersensitivity to lipopolysaccharide . In addition, ageing knockout mice exhibited a distinct phenotype of delayed senility, accompanied by a considerable reduction in adipose mass, indicating that UBD is key regulator of the inflammatory response and fat metabolism . These data highlight the potential role of UBD in regulating lipogenesis in mice adipose tissue, which is a vital energy storage tissue.…”

“…These data highlight the potential role of UBD in regulating lipogenesis in mice adipose tissue, which is a vital energy storage tissue. Although UBD plays a critical role in various intracellular activities, such as inflammation, apoptosis and tumourigenesis, whether it can modulate adipogenesis is still unclear . Therefore, this study tried to elucidate the effect of UBD on lipogenesis in porcine preadipocytes.…”

The Ubiquitin-like Modifier FAT10 Is Selectively Expressed in Medullary Thymic Epithelial Cells and Modifies T Cell Selection

“…Analysis of FAT10-deficient mice demonstrated an enhanced sensitivity toward endotoxin challenge (13). Additionally, FAT10 2/2 mice have an extended lifespan and reduced adiposity compared with wild-type mice (21). In this study, we could assign the previously recognized high FAT10 expression in the thymus (14) to terminally differentiated mTECs.…”