Targeting liver and adipose tissue in obese mice: Effects of a N-acylethanolamine mixture on insulin resistance and adipocyte reprogramming.

Autor: Melini S; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy., Lama A; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy., Comella F; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy., Opallo N; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy., Del Piano F; Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples 80137, Italy., Annunziata C; Department of Bioscience and Nutrition Karolinska Institute Neo Building, Huddinge 14152, Sweden., Mollica MP; Department of Biology, University of Naples Federico II, Naples 80126, Italy., Ferrante MC; Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples 80137, Italy., Pirozzi C; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy. Electronic address: claudio.pirozzi@unina.it., Mattace Raso G; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy., Meli R; Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80131, Italy.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 May; Vol. 174, pp. 116531. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1016/j.biopha.2024.116531
Abstrakt: N-acylethanolamines (NAEs) are endogenous lipid-signalling molecules involved in inflammation and energy metabolism. The potential pharmacological effect of NAE association in managing inflammation-based metabolic disorders is unexplored. To date, targeting liver-adipose axis can be considered a therapeutic approach for the treatment of obesity and related dysfunctions. Here, we investigated the metabolic effect of OLALIAMID® (OLA), an olive oil-derived NAE mixture, in limiting liver and adipose tissue (AT) dysfunction of high-fat diet (HFD)-fed mice. OLA reduced body weight and fat mass in obese mice, decreasing insulin resistance (IR), as shown by homeostasis model assessment index, and leptin/adiponectin ratio, a marker of adipocyte dysfunction. OLA improved serum lipid and hepatic profile and the immune/inflammatory pattern of metainflammation. In liver of HFD mice, OLA treatment counteracted glucose and lipid dysmetabolism, restoring insulin signalling (phosphorylation of AKT and AMPK), and reducing mRNAs of key markers of fatty acid accumulation. Furthermore, OLA positively affected AT function deeply altered by HFD by reprogramming of genes involved in thermogenesis of interscapular brown AT (iBAT) and subcutaneous white AT (scWAT), and inducing the beigeing of scWAT. Notably, the NAE mixture reduced inflammation in iBAT and promoted M1-to-M2 macrophage shift in scWAT of obese mice. The tissue and systemic anti-inflammatory effects of OLA and the increased expression of glucose transporter 4 in scWAT contributed to the improvement of gluco-lipid toxicity and insulin sensitivity. In conclusion, we demonstrated that this olive oil-derived NAE mixture is a valid nutritional strategy to counteract IR and obesity acting on liver-AT crosstalk, restoring both hepatic and AT function and metabolism.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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