Background and purpose
Nuciferine, an alkaloid found in the Nelumbo nucifera leaf, alleviates dyslipidemia in vivo. However, whether it improves liver injury in diabetic conditions and the underlying mechanism is unclear. The present study aimed to investigate the effects of nuciferine on lipid and glucose metabolism in a murine model of T2DM, and to determine the underlying mechanisms of these effects.
Experimental approach
A murine model of T2DM was induced by high fat diet (HFD) feeding combined with streptozocin (STZ) injections, and the diabetic mice were treated with nuciferine. The underlying mechanism of the anti‐steatotic effect of nuciferine was further explored in HepG2 hepatocytes cultured with palmitic acid. Major signaling profiles involved in fatty acid oxidation were then evaluated.
Key results
Nuciferine restored impaired glucose tolerance and insulin resistance in the diabetic mice. Hepatic levels of total cholesterol, triglycerides and low‐density lipoprotein were significantly decreased, as well as the number of lipid droplets in the nuciferine treated mice. Furthermore, nuciferine upregulated β‐oxidation related genes in the liver of diabetic mice. Luciferase reporter cell assay showed that nuciferine directly reversed palmitic acid‐induced inhibition of PPARα transcriptional activity. Silencing peroxisome proliferator activated receptor coactivator‐1α (PGC1α) expression in HepG2 cells abolished the effects of nuciferine in accelerating β‐oxidation.
Conclusions and implications
Our results demonstrated that nuciferine improved lipid profile and attenuated hepatic steatosis in HFD/STZ‐induced diabetic mice by activating the PPARα/PGC1α pathway. Nuciferine may be a potentially important candidate in improving hepatic steatosis and the management of T2DM.
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Materials
Nuciferine was purchased from Chengdu
Biopurify
Phytochemicals Ltd. (Chengdu, China). Human insulin (Humulin? R) …
