Page 40 - N. Metabolism and metabolic diseases

[N. Metabolism and metabolic diseases-22]

MKRN1 deficiency attenuates metabolic syndrome via AMPK

stabilization and activation

Seungyeon Kim¹, Jaewhan Song¹˙*

¹Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea

The 5' adenosine monophosphate-activated protein kinase (AMPK) is an essential cellular energy sensing enzyme,
which maintains ATP to restore energy homeostasis. The activation of AMPK is associated with various cellular
metabolic processes, including suppression of gluconeogenesis, lipogenesis, promotion of glucose consumption,

and fatty acid oxidation. Therefore, AMPK activation is significant to prevent and ameliorate metabolic disorders

such as type II diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases. Although
regulation of AMPK stability in energy metabolism is considerable, an E3 ubiquitin ligase for AMPK that controls
systemic metabolism is yet to be reported. Here, we investigated that makorin ring finger protein 1 (MKRN1) acts

as an E3 ubiquitin ligase for AMPK. MKRN1 deficiency reduced high-fat diet (HFD)- induced obesity and reversed
NAFLD by stabilizing and activating AMPK. Moreover, MKRN1 ablation altered lipid and glucose metabolism in the

liver and adipose tissues. Taken together, our findings suggest that MKRN1 may serve as a possible therapeutic
target for metabolic syndromes.