Major royal jelly proteins prevents NAFLD by improving mitochondrial function and lipid accumulation through activating the AMPK / SIRT3 pathway in vitro

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome, whose main characteristics are excessive lipid accumulation and oxidative stress. Major royal jelly proteins (MRJPs) is a kind of water‐soluble protein, which is abundant in royal jelly (RJ). The aim of this study was to evaluate the effect of MRJPs on lipid accumulation and oxidative stress of liver cells. Here, we first optimized the conditions for extracting MRJPs from RJ and identified the extraction effect and product by SDS‐PAGE. Then, we used oleic acid (OA) of 1.0 mM to induce hepatocytes for 24 hr to establish a stable cell models of lipid accumulation, and we found that pre‐administration (24 hr) of MRJPs (0.2, 0.5, and 1.0 g/L) could significantly reduce the lipid drop content and triglyceride level in the model cells, and simultaneously reduce the alanine aminotransferase and aspertate aminotransferase levels in the cell culture supernatant. In addition, pre‐incubation (24 hr) with MRJPs (0.2, 0.5, and 1.0 g/L) could restore superoxide dismutase (SOD) level and mitochondrial membrane potential as compared with OA group. Furthermore, MRJPs administration significantly upregulated the expression of Silent Information Regulator 2 Associated Protein 3, mitochondrial superoxide dismutase (SOD2), and cytochrome c oxidase subunit IV in OA‐treated HepG2 cells. The study for the first time provides evidences on the lipid‐lowering effect of MRJPs at the cellular level, which can further provide support for the development and application of polypeptide drugs in the future, and can also provide a choice for the prevention and treatment of liver metabolic diseases represented by NAFLD. Practical Application Our study proved that MRJPs had substantial preventing effect on OA‐induced lipid accumulation and mitochondrial dysfunction in HepG2 cells. This research can further provide theoretical support for the development and application of peptide drugs in the future. Besides, it can not only further broaden our understanding of NAFLD and other diseases, but also provide ideas for research on oxidative stress and lipid accumulation in the body.

Effects of Major Royal Jelly Proteins on the Immune Response and Gut Microbiota Composition in Cyclophosphamide-Treated Mice

“…Extraction of proteins: An analysis of three biological replicates was processed in both ways with proteomics. The method of extracting protein from the RJ and MRJPs for proteomic analysis was described by previous reports, with some modifications [ 17 ]. Briefly, the RJ and MRJPs were each mixed with a Lysis buffer (1:1, v / v ) and ultrasonicated for 2 min using an ultrasonic cell crusher at 4 °C.…”

Progress in Nonalcoholic Fatty Liver Disease: SIRT Family Regulates Mitochondrial Biogenesis

“…However, there is evidence that SIRT3 knockout mice induced by HFD show severe metabolic syndrome [ 139 ]. Pharmacological stimulation of SIRT3, PGC1α, nuclear respiratory factor-1, and FoxO3 mRNA expression or activation of the SIRT3-AMPK-PGC1α-ERRα signaling pathway can improve mitochondrial dysfunction and oxidative stress [ 145 , 146 , 147 ]. FoxO3 is the direct target of SIRT3, and its function is to regulate the expression of multiple genes as a forked transcription factor [ 148 ].…”

Modulation of Oxidative Stress-Induced Senescence during Non-Alcoholic Fatty Liver Disease

“…[138]. The beneficial effects of SIRT3 in NAFLD have been linked to improved mitochondrial function and reduced lipid accumulation via AMPK activation [139]. Furthermore, SIRT3 has been shown to increase mitophagy and prevent mitochondria-mediated hepatocyte apoptosis [140].…”