Distinct AMPK-Mediated FAS/HSL Pathway Is Implicated in the Alleviating Effect of Nuciferine on Obesity and Hepatic Steatosis in HFD-Fed Mice

Abstract

Nuciferine (Nuci), the main aporphine alkaloid component in lotus leaf, was reported to reduce lipid accumulation in vitro. Herein we investigated whether Nuci prevents obesity in high fat diet (HFD)-fed mice and the underlying mechanism in liver/HepG2 hepatocytes and epididymal white adipose tissue (eWAT) /adipocytes. Male C57BL/6J mice were fed with HFD supplemented with Nuci (0.10%) for 12 weeks. We found that Nuci significantly reduced body weight and fat mass, improved glycolipid profiles, and enhanced energy expenditure in HFD-fed mice. Nuci also ameliorated hepatic steatosis and decreased the size of adipocytes. Furthermore, Nuci remarkably promoted the phosphorylation of AMPK, suppressed lipogenesis (SREBP1, FAS, ACC), promoted lipolysis (HSL, ATGL), and increased the expressions of adipokines (FGF21, ZAG) in liver and eWAT. Besides, fatty acid oxidation in liver and thermogenesis in eWAT were also activated by Nuci. Similar results were further observed at cellular level, and these beneficial effects of Nuci in cells were abolished by an effective AMPK inhibitor compound C. In conclusion, Nuci supplementation prevented HFD-induced obesity, attenuated hepatic steatosis, and reduced lipid accumulation in liver/hepatocytes and eWAT/adipocytes through regulating AMPK-mediated FAS/HSL pathway. Our findings provide novel insight into the clinical application of Nuci in treating obesity and related complications.

JianPi-QingHua formula attenuates nonalcoholic fatty liver disease by regulating the AMPK/SIRT1/NF-κB pathway in high-fat-diet-fed C57BL/6 mice

“… 2020 ; Xu et al. 2022 ). The expression of AMPK and SIRT1 in the liver is reduced in HFD-fed mice for 12 weeks (Xu et al.…”

“…The expression of AMPK and SIRT1 in the liver is reduced in HFD-fed mice for 12 weeks (Xu et al. 2022 ). Activation of AMPK/SIRT1 pathway protects against NAFLD, accompanied by inhibition of lipogenesis (Garcia et al.…”

“…Meanwhile, increasing evidence indicates that the reduced AMPK activity in the liver occurs in HFD-induced animals (Xu et al. 2022 ), which is bolstered by the antidiabetic drug metformin (Yan et al. 2019 ; Zamani-Garmsiri et al.…”

N-linoleyltyrosine ameliorates high-fat diet-induced obesity in C57BL/6 mice via cannabinoid receptor regulation

“…AMPK is an AMP-dependent protein kinase, which plays a role in energy homeostasis through the upregulation of catabolic processes that generate ATP. AMPK activation enhances the catabolism of the body, and reduce the expression of lipid synthesis-related factors such as FAS to regulate the synthesis and utilization of lipids ( 42 ). FAS is a key enzyme in lipogenesis, and when activated, it increases fatty acid synthesis and insulin resistance in adipose tissues.…”

Nuciferine Ameliorates Nonesterified Fatty Acid-Induced Bovine Mammary Epithelial Cell Lipid Accumulation, Apoptosis, and Impaired Migration via Activating LKB1/AMPK Signaling Pathway

“…For instance, the protective effects of nuciferine against liver injury and steatosis through PPARα/PPARγ coactivator-1α (PGC-1α) pathway in high-fat diet (HFD)-fed induced diabetic mice have been reported . In addition, nuciferine has been shown to activate AMPK to attenuate HFD-induced lipid overload in hepatocytes and adipocytes . However, no attention has been paid to the effect of nuciferine on lipotoxicity in bMECs.…”