Souza-Tavares H, Miranda CS, Vasques-Monteiro IML, Sandoval C, Santana-Oliveira DA, Silva-Veiga FM, Fernandes-da-Silva A, Souza-Mello V. Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas. World J Gastroenterol 2023; 29(26): 4136-4155 [PMID: 37475842 DOI: 10.3748/wjg.v29.i26.4136]
Corresponding Author of This Article
Vanessa Souza-Mello, PhD, Associate Professor, Department of Anatomy, Rio de Janeiro State University, Blvd. 28 de setembro 87, fundos, Rio de Janeiro 20551030, Brazil. souzamello.uerj@gmail.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Henrique Souza-Tavares, Carolline Santos Miranda, Isabela Macedo Lopes Vasques-Monteiro, Daiana Araujo Santana-Oliveira, Flavia Maria Silva-Veiga, Aline Fernandes-da-Silva, Vanessa Souza-Mello, Department of Anatomy, Rio de Janeiro State University, Rio de Janeiro 20551030, Brazil
Cristian Sandoval, Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Osorno 5310431, Chile
Cristian Sandoval, Departamento de Ciencias Preclínicas, Universidad de la Frontera, Temuco 4780000, Chile
Author contributions: Souza-Mello V and Souza-Tavares H conceived the idea for the manuscript; Souza-Tavares H, Miranda CS, Vasques-Monteiro IML, Sandoval C, Santana-Oliveira DA, Silva-Veiga FM, Fernandes-da-Silva A, and Souza-Mello V performed the literature search and drafted the manuscript; Santana-Oliveira DA, Silva-Veiga FM, and Souza-Mello V designed the figures; Souza-Mello V critically revised the work; and all authors read and approved the final version of the manuscript.
Supported bythe Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil), No. 303785/2020-9; and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, No. E-26/200.984/2022 for V.S-M.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vanessa Souza-Mello, PhD, Associate Professor, Department of Anatomy, Rio de Janeiro State University, Blvd. 28 de setembro 87, fundos, Rio de Janeiro 20551030, Brazil. souzamello.uerj@gmail.com
Received: April 21, 2023 Peer-review started: April 21, 2023 First decision: May 15, 2023 Revised: May 26, 2023 Accepted: June 13, 2023 Article in press: June 13, 2023 Published online: July 14, 2023 Processing time: 79 Days and 16.7 Hours
Abstract
The world is experiencing reflections of the intersection of two pandemics: Obesity and coronavirus disease 2019. The prevalence of obesity has tripled since 1975 worldwide, representing substantial public health costs due to its comorbidities. The adipose tissue is the initial site of obesity impairments. During excessive energy intake, it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs. The pancreas is one of the organs most affected by obesity. Once lipotoxicity becomes chronic, there is an increase in insulin secretion by pancreatic beta cells, a surrogate for type 2 diabetes mellitus (T2DM). These alterations threaten the survival of the pancreatic islets, which tend to become dysfunctional, reaching exhaustion in the long term. As for the liver, lipotoxicity favors lipogenesis and impairs beta-oxidation, resulting in hepatic steatosis. This silent disease affects around 30% of the worldwide population and can evolve into end-stage liver disease. Although therapy for hepatic steatosis remains to be defined, peroxisome proliferator-activated receptors (PPARs) activation copes with T2DM management. Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways, leading to insulin resistance relief, improved thermogenesis, and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation. This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases, focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.
Core Tip: The world faces a pandemic of obesity and metabolic diseases. Peroxisome proliferator-activated receptors’ (PPARs’) target genes regulate several metabolic pathways, alleviating obesity and its metabolic impairments. PPARα exerts relevant anti-inflammatory, anti-steatotic, and pro-thermogenic effects, collaborating with weight loss and insulin resistance alleviation. PPARγ is useful for glycemic management, albeit with caution due to side effects after its total activation. PPARβ/δ is not clinically used owing to a pro-tumorigenic profile. However, Pan-PPAR or dual-PPAR agonists can retain PPARβ/δ or partial PPARγ activation benefits and configure promising approaches to treat metabolic diseases alone or in combination with other drug classes.
