Page 38 - N. Metabolism and metabolic diseases
P. 38
[N. Metabolism and metabolic diseases-21]
Loss of the E3 ubiquitin ligase MKRN1 represses NAFLD
(Non-alcoholic fatty liver disease) through AMPK activation
Hyun-Ji Han¹, Jaewhan Song¹˙*
¹Biochemistry, Yonsei University, Seoul 03722, Republic of Korea
Non-alcoholic fatty liver disease (NAFLD) is an important risk factor for chronic metabolic syndrome. NAFLD is
advanced in patients with non-alcoholic steatohepatitis (NASH) or cirrhosis and cancer through a high nutrient
condition . Accordingly, the rapidly increasing prevalence of NAFLD would require novel therapeutic approaches
based on hepatic lipid accumulation. Here, we report the identification of Makorin ring finger protein 1 (MKRN1)
as a novel regulator to prevent NAFLD. MKRN1 acts as an E3 ubiquitin ligase for the AMP-activated protein kinase
(AMPK). AMPK is a master regulator of energy metabolism in response to nutritional status. MKRN1-depleted mice
showed AMPK activation in the liver, resulting in the significant suppression of diet-induced metabolic syndrome.
Moreover, we demonstrated the therapeutic effect of MKRN1 using MKRN1-depleted high-nutrient-fed mice that
reversed the non-alcoholic fatty liver disease. We suggest that MKRN1 repression could be a potential therapeutic
strategy for metabolic disorders .
