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World J Gastroenterol. Jul 7, 2023; 29(25): 3999-4008
Published online Jul 7, 2023. doi: 10.3748/wjg.v29.i25.3999
Insulin resistance and adipose tissue interactions as the cornerstone of metabolic (dysfunction)-associated fatty liver disease pathogenesis
Shreya C Pal, Nahum Méndez-Sánchez
Shreya C Pal, Nahum Méndez-Sánchez, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
Shreya C Pal, Nahum Méndez-Sánchez, Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City 04510, Mexico
Author contributions: Pal SC contributed to manuscript writing, data analysis, and critical revision; Méndez-Sánchez N contributed to conceptualization, manuscript design, critical revision, and supervision.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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:
Corresponding author: Nahum Méndez-Sánchez, FAASLD, AGAF, FACG, MD, MSc, PhD, Researcher, Liver Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Col. Toriello Guerra, Mexico City 04510, Mexico.
Received: December 6, 2022
Peer-review started: December 6, 2022
First decision: January 22, 2023
Revised: February 9, 2023
Accepted: March 20, 2023
Article in press: March 20, 2023
Published online: July 7, 2023

The relationship between metabolic derangements and fatty liver development are undeniable, since more than 75% of patients with type 2 diabetes mellitus present with fatty liver. There is also significant epidemiological association between insulin resistance (IR) and metabolic (dysfunction)-associated fatty liver disease (MAFLD). For little more than 2 years, the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups. While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed, the bottom line relies on the role of IR as an initiator and perpetuator of this disease. There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations, where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory element-binding protein-1c induced lipogenic enzyme stimulation; therefore, increased endogenous production of triglycerides. The same effect is achieved through impaired suppression of adipose tissue (AT) lipolysis in insulin-resistant states, increasing fatty acid influx into the liver. The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion, modifying fatty acid metabolism as well as IR in a variety of tissues, including skeletal muscle, AT, and the liver. The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

Keywords: Metabolic (dysfunction)-associated fatty liver disease, Insulin resistance, Adipose tissue, Fatty liver, Metabolic syndrome, Adipokine

Core Tip: In this review, we outline the main arguments that support the importance of insulin resistance (IR) in fatty liver pathogenesis, stressing its role in metabolic dysfunction. IR and other genetic and molecular mechanisms play a pivotal role not only in metabolic dysfunction–associated fatty liver disease development but also in some of its complications and comorbidities, such as chronic kidney disease.