123-OR: MiR103 as a Potential Inhibitor for Dyslipidemia through Modulation of ANGPTL8 Level

There is increasing interest in the role of epigenetic factors in obesity and its impact on diabetes and dyslipidemia. Earlier report found that miR-103 suppresses de novo lipogenesis (DNL) and dampens the development of obesity/diet-induced fatty liver through targeting at Fasn and Scd1 genes in mouse liver. On the other hand, lipid regulating hormone angiopoietin-like 8 (ANGPTL8) is a known regulator of triglycerides through its inhibition of the lipoprotein lipase activity through its interaction with ANGPTL3. We aimed to study the miR-103 expression in the blood and adipose tissue in a cohort of obese and non-obese people and confirm its binding and regulation to ANGPTL8. miR-103 expression levels were investigated using RT-PCR in 144 participants, 82 who were non-obese (body mass index [BMI] <30) and 62 who were obese (BMI >30). Overexpression and luciferase assays were used to confirm the binding between miR-103 and ANGPTL8. The plasma levels of ANGPTL8 were also measured by ELISA. The miR-103 levels were significantly lower in obese than in non-obese individuals (P = 0.002). In vitro analysis confirmed miR-103 binding to and repression of the ANGPTL8 transcript and protein. Obesity leads to alterations in miR-103 expression. Its downregulation in obese humans was inversely correlated with ANGPTL8, a protein involved in lipid metabolism. Further, miR-103 plasma levels were inversely correlated with TG levels (P = 0.011), and ANGPTL8 levels were positively correlated with TG levels. miR-103 can be used as an inhibitor of ANGPTL8 to reduce the TG plasma level and mitigate dyslipidemia.