Nobiletin alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating AdipoR1 and gp91phox expression in rats

Sarawoot Bunbupha; Poungrat Pakdeechote; Putcharawipa Maneesai; Patoomporn Prasarttong

doi:10.1016/j.jnutbio.2020.108526

Nobiletin alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating AdipoR1 and gp91^phox expression in rats

J Nutr Biochem. 2021 Jan:87:108526. doi: 10.1016/j.jnutbio.2020.108526. Epub 2020 Oct 20.

Authors

Sarawoot Bunbupha¹, Poungrat Pakdeechote², Putcharawipa Maneesai², Patoomporn Prasarttong²

Affiliations

¹ Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand. Electronic address: sarawoot.b@msu.ac.th.
² Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.

PMID: 33096235
DOI: 10.1016/j.jnutbio.2020.108526

Abstract

Nobiletin, one of the polymethoxylated flavonoids isolated from citrus peels, is reported to possess various biological activities. The current study investigates the effect and possible mechanisms of nobiletin on nonalcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-fed rats. Male Sprague-Dawley rats were administrated with HFD and fructose (15%) in drinking water for 16 weeks to induce NAFLD. HFD-fed rats were treated with nobiletin (20 or 40 mg/kg/day) or vehicle for the last 4 weeks. Treatment of HFD-fed rats with nobiletin significantly reduced systolic blood pressure, adiposity, hyperlipidemia, insulin resistance, hepatic lipids content, NAFLD activity score and liver fibrosis. Nobiletin significantly increased plasma adiponectin levels, together with up-regulation of liver adiponectin receptor 1 (AdipoR1) expression. Additionally, decreased malondialdehyde levels and increased superoxide dismutase activity in plasma and hepatic tissue, consistent with down-regulation of liver NADPH oxidase subunit gp91^phox expression, were also observed after nobiletin treatment. Furthermore, high dose of nobiletin exhibited higher therapeutic effect as a compared to low dose. These findings suggest that nobiletin alleviates HFD-induced NAFLD and metabolic dysfunction in rats. There might be an association between the observed inhibitory effect of nobiletin on NAFLD and modulation of AdipoR1 and gp91^phox.

Keywords: High-fat diet; Metabolic dysfunction; Nobiletin; Nonalcoholic fatty liver disease; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / therapeutic use*
Diet, High-Fat / adverse effects
Flavones / therapeutic use*
Liver / drug effects
Liver / pathology
Male
NADPH Oxidase 2 / analysis*
Non-alcoholic Fatty Liver Disease / drug therapy*
Non-alcoholic Fatty Liver Disease / etiology
Non-alcoholic Fatty Liver Disease / pathology
Rats
Rats, Sprague-Dawley
Receptors, Adiponectin / analysis*

Substances

Antioxidants
Flavones
Receptors, Adiponectin
adiponectin receptor 1, rat
nobiletin
Cybb protein, rat
NADPH Oxidase 2