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Published on: November 27, 2019
[Metformin reduces plasma triglycerides in ob/ob obese mice via inhibiting the hepatic apoA5 expression]
Xiansheng Huang1, Rong Li2, Luzhu Chen3
1Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China initialhxs@163.com.
Objective:
To investigate the role of apolipoprotein A5 (apoA5) in the pathogenesis of obesity-related hypertriglyceridemia and the related therapeutic effects of metformin. Methods: The ob/ob mice were treated with regular chow diet and metformin for 4 weeks, and the levels of hepatic triglyceride (TG) and apoA5 were measured. Hepatic IAR20 cells were treated with metformin and/or apoA5 siRNAs, and then cellular TG contents and apoA5 expression were determined. Results: High plasma and hepatic levels of apoA5 and TG were found in ob/ob mice. The plasma levels of apoA5 were positively correlated with plasma TG in these mice. Metformin could dose-dependently decrease the plasma and hepatic levels of apoA5 and TG in ob/ob mice. Metformin could also dose-dependently reduce cellular TG contents and apoA5 expression, these effects were attenuated by knockdown of apoA5. Conclusion: Hepatic apoA5 is up-regulated in ob/ob mice, which contributes to the elevation of plasma TG. Metformin could inhibit hepatic apoA5 expression, leading to the reduction of the plasma level of TG.
Insights
Metformin reduces high triglyceride levels in obesity by lowering apolipoprotein A5 (apoA5) expression in the liver. This study shows apoA5 contributes to obesity-related hypertriglyceridemia.
Area of Science:
- Biochemistry
- Metabolic Diseases
- Pharmacology
Background:
- Obesity-related hypertriglyceridemia is a significant metabolic disorder.
- Apolipoprotein A5 (apoA5) is implicated in triglyceride metabolism.
Purpose of the Study:
- To investigate the role of apoA5 in obesity-induced hypertriglyceridemia.
- To evaluate the therapeutic effects of metformin on apoA5 and triglyceride levels.
Main Methods:
- Utilized ob/ob mice model and hepatic IAR20 cells.
- Administered metformin and/or apoA5 siRNAs.
- Measured plasma and hepatic triglyceride (TG) and apoA5 levels, as well as cellular TG content and apoA5 expression.
Main Results:
- Ob/ob mice exhibited elevated plasma and hepatic apoA5 and TG levels, with a positive correlation between plasma apoA5 and TG.
- Metformin treatment dose-dependently reduced plasma and hepatic apoA5 and TG levels in ob/ob mice.
- Metformin decreased cellular TG and apoA5 expression, an effect diminished by apoA5 knockdown.
Conclusions:
- Hepatic apoA5 upregulation contributes to hypertriglyceridemia in obesity.
- Metformin exerts therapeutic effects by inhibiting hepatic apoA5 expression, thereby reducing plasma TG levels.
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