n/a
Article Publish Status: FREE
Abstract Title:

The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat fed- mice independent of AMPK.

Abstract Source:

J Lipid Res. 2020 Jan 21. Epub 2020 Jan 21. PMID: 31964763

Abstract Author(s):

Nadya M Morrow, Amy C Burke, Joshua P Samsoondar, Kyle E Seigel, Andrew Wang, Dawn E Telford, Brian G Sutherland, Conor O'Dwyer, Gregory R Steinberg, Morgan D Fullerton, Murray W Huff

Article Affiliation:

Nadya M Morrow

Abstract:

Obesity, dyslipidemia, and insulin resistance-the increasingly common metabolic syndrome-are risk factors for cardiovascular disease and type 2 diabetes that warrant novel therapeutic interventions. The flavonoid nobiletin displays potent lipid-lowering and insulin-sensitizing properties in mice with metabolic dysfunction. However, the mechanisms by which nobiletin mediates metabolic protection are not clearly established. The central role of AMP-activated protein kinase (AMPK) as an energy sensor suggests that AMPK is a target of nobiletin. We tested the hypothesis that metabolic protection by nobiletin required phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in mouse hepatocytes, in mice deficient in hepatic AMPK (), in mice incapable of inhibitory phosphorylation of ACC () and in mice with adipocyte-specific AMPK deficiency (). We fed mice a high-fat/high-cholesterol diet with or without nobiletin. Nobiletin increased phosphorylation of AMPK and ACC in primary mouse hepatocytes, which was associated with increased fatty acid (FA) oxidation and attenuated FA synthesis. Despite loss of ACC phosphorylation inhepatocytes, nobiletin suppressed FA synthesis and enhanced FA oxidation. Acute injection of nobiletin into mice did not increase phosphorylation of either AMPK or ACC in liver. In mice fed a high-fat diet, nobiletin robustly prevented obesity, hepatic steatosis, dyslipidemia and insulin resistance, and it improved energy expenditure in,andmice to the same extent as in wild-type controls. Thus, the beneficial metabolic effects of nobiletinare conferred independently of hepatic or adipocyte AMPK activation. These studies further underscore the therapeutic potential of nobiletin and begin to clarify possible mechanisms.

Print Options


Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2020 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.