Systemic metabolic syndrome significantly increases the risk of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, no effective therapeutic strategies are available, practically because our understanding of its complicated pathogenesis is poor. Here we identify the tripartite motif-containing protein 31 (Trim31) as an endogenous inhibitor of rhomboid 5 homolog 2 (Rhbdf2), and we further determine that Trim31 directly binds to Rhbdf2 and facilitates its proteasomal degradation. Hepatocyte-specific Trim31 ablation facilitates NAFLD-associated phenotypes in mice. Inversely, transgenic or ex vivo gene therapy-mediated Trim31 gain-of-function in mice with NAFLD phenotypes virtually alleviates severe deterioration and progression of steatohepatitis. The current findings suggest that Trim31 is an endogenous inhibitor of Rhbdf2 and downstream cascades in the pathogenic process of steatohepatitis and that it may serve as a feasible therapeutical target for the treatment of NAFLD/NASH and associated metabolic disorders.

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ObjectiveWhether sarcopenia is detrimental to depression is still controversial, which may be due to the three components of the sarcopenia. Our objective was to define the correlation between depression and sarcopenia in older Chinese community dwellers.DesignThe study has a cross-sectional design.SettingThe study was conducted in Jiangsu, China.ParticipantsA total of 101 men and 149 women aged 60 years or older were recruited.Outcome measuresLean tissue mass was measured by dual-energy X-ray absorptiometry. Muscle strength in the upper and lower limbs was measured by a handheld dynamometer and a chair stand test, respectively. Physical performance was assessed by gait speed and standing balance tests. Depressive mood was assessed using the Geriatric Depression Scale-30 (range 0–30).ResultsParticipants in the sarcopenia group had a higher mean depression score than the normal group (p=0.002). Pearson’s correlation analysis showed that depression was negatively associated with muscle strength (handgrip strength: R=−0.170, p=0.028 for women, R=−0.196, p=0.048 for men; chair stand test performance: R=0.252, p=0.002 for women, R=0.311, p=0.001 for men) and physical performance (gait speed: R=−0.200, p=0.009, standing balance test performance: R=−0.224, p=0.006, Short Physical Performance Battery (SPPB): R=−0.218, p=0.007 for women; SPPB: R=−0.252, p=0.01 for men). Multiple linear regression models revealed that depressive mood was inversely associated with chair stand test (β=0.325, p<0.001), gait speed (β=−0.009, p=0.041) and standing balance test (β=−0.24, p=0.016) after adjusting for confounding factors, while no significant correlation was observed between depressive mood and muscle mass.ConclusionThe diagnostic components of sarcopenia—strength of the leg muscles (chair stand test) and physical performance (gait speed and standing balance test)—were associated with depressive mood.

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