Life Extension in Mice via FAT10 Knockout

Visceral fat is harmful to long term health, such as through its promotion of chronic inflammation, among other mechanisms. It is known that surgical removal of visceral fat in mice can extend life, for example. So it is plausible that the mechanism of action for the genetic alteration noted in the paper quoted below is in fact lower levels of fat, but as for all such things it will require much more work to determine whether or not this is the case. So many aspects of metabolism are changed, they all impact one another, and picking apart individual mechanisms is a challenging process. There are many ways to extend life in mice through metabolic alteration, and it is fair to say that none are yet fully understood.

The HLA-F adjacent transcript 10 (FAT10) is a member of the ubiquitin-like 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 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.

If the role of FAT10 in humans is similar to mice, then targeting of FAT10 may hold promising therapeutic impact for the treatment of various diseases including obesity and obesity-related diseases and aging associated diseases.


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