Adeno-Associated Virus-Mediated Knockdown of SLC16A11 Improves Glucose Tolerance and Hepatic Insulin Signaling in High Fat Diet-Fed Mice.

Tan Zhang, Zhengtang Qi, Haiyan Wang, Shuzhe Ding

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2021 Feb

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SLC16A11, a member of the SLC16 family, is associated with lipid metabolism, causing increased intracellular triacylglycerol (TAG) levels. In the current study, our primary goal was to determine if an SLC16A11 knockdown would improve glucose tolerance and hepatic insulin signaling in high fat diet (HFD)-fed mice. Additionally, the mechanism for exercise-improved insulin sensitivity remains unclear, and there is no mechanistic insight into SLC16A11's role in insulin sensitivity under exercise stress. Therefore, we also examined the impact of endurance exercise on the abundance of SLC16A11. C57BL/6 J male mice were fed either regular chow (Control) or HFD for 8 weeks and then injected with adeno-associated virus (AAV). Plasma parameters, tissue lipid contents, glucose tolerance, and expression profiles of hepatic insulin signaling were detected. Also, other mice were divided randomly into sedentary and exercise groups. We assessed hepatic expression of SLC16A11 after 8 weeks of endurance exercise. 1) Hepatic SLC16A11 expression was greater in HFD-fed mice compared to Control mice. 2) AAV-mediated knockdown of SLC16A11 improved glucose tolerance, prevented TAG accumulation in serum and liver, and increased phosphorylation of protein kinase B (Akt) and glycogen synthesis kinase-3β (GSK3β) in HFD-fed mice. 3) Endurance exercise decreased hepatic SLC16A11 expression. Inactivation of SLC16A11, which is robustly induced by HFD, improved glucose tolerance and hepatic insulin signaling, independent of body weight, but related to TAG. Additionally, SLC16A11 might mediate the health benefits of endurance exercise. Thieme. All rights reserved.

Citation

Tan Zhang, Zhengtang Qi, Haiyan Wang, Shuzhe Ding. Adeno-Associated Virus-Mediated Knockdown of SLC16A11 Improves Glucose Tolerance and Hepatic Insulin Signaling in High Fat Diet-Fed Mice. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2021 Feb;129(2):104-111