Page 250 - ebook

[D. Medicine/Translational Research] D-9

Mig-6 mediates brown adipocyte differentiation, glucose

homeostasis and thermogenesis in BAT

Sorim Choung¹,², Jun Choul Lee², Ji Min Kim³, Kyong Hye Joung³, Hyun Jin Kim², Bon Jeong Ku¹,²*

¹Reserch Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 35015,

Korea, ²Department of Internal Medicine, College of Medicine, Chungnam National University School of Medicine,

Daejeon 35015, Korea, ³Department of Endocrinology, Chungnam National University Sejong Hospital, Sejong
30099, Korea

Stimulating the metabolic function of BAT, represent potential therapeutic strategies for increasing energy

expenditure and reducing obesity. Mitogen-inducible gene 6 (Mig-6), a tumor suppressor gene, is a negative
regulator of the EGFR signal. In previous study, we demonstrated the association between EGFR signaling and

NAFLD. However, the roles of Mig-6 in BAT remain poorly understood. We down-regulated the expression of Mig-
6, using lentivirus mediated shRNA by transducing immortalized brown adipocytes. We generated mice enhacing

Mig-6 in BAT using a genetic strategy based on the Cre-ROSA recombination. Here, we showed that the inhibition
of Mig-6 declined differentiation and thermogenesis in the BAT cell. Mig-6 BKI mice showed better metabolic

phenotypes, including improved glucose metabolism, lipid levels, fasting glucose. We detected a reduction in the
size of adipocyte and a relative increase of UCP1 expression by anti-UCP1 IHC in Mig-6 KI BAT. Of note, Mig-6

augmented the expression of thermogenesis relative genes, consistent with the increased UCP1 in the BAT of mice.
In conclusion, Mig-6 is as potential factor improving obesity by regulating differentiation, glucose metabolism and
thermogenesis in the BAT.