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NAD+-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin

Theranostics

February 25, 2021

Li, Dong-Jie

Summary

We investigated the involvement of fibronectin type III domain containing 5 (Fndc5) or irisin, which is a novel exercise-linked hormone, in the development and progression of nonalcoholic fatty liver disease (NAFLD). NR treatment elevated plasma level of Fndc5/irisin in mice and human volunteers. NR treatment also increased Fndc5 expression in skeletal muscle, adipose and liver tissues in mice. In HFD-induced NAFLD mice model, NR displayed remarkable therapeutic effects on body weight gain, hepatic steatosis, steatohepatitis, insulin resistance, mitochondrial dysfunction, apoptosis and fibrosis; however, these actions of NR were compromised in Fndc5-/- mice. Chronic infusion of recombinant Fndc5/irisin alleviated the NAFLD pathological phenotypes in MCD-induced NAFLD mice model...The findings from this research for the first time demonstrate that NAD+-boosting therapy reverses NAFLD by regulating SIRT2-deppendent Fndc5 deacetylation and deubiquitination, which results in a stimulation of Fndc5/irisin, a novel exerkine. These results suggest that Fndc5/irisin may be a potential nexus between physical exercise and NAD+-boosting therapy in metabolic pathophysiology.

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Original work © 2022 by Right of Assembly

No claim to research or any work of others

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1. Health Supplements Are Not Medicines. Health Supplements that raise NAD levels, like nicotinamide riboside or other NAD precursors, are not intended to diagnose, treat, cure, or prevent any disease.

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