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Abstract Details
The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications
J Clin Med. 2022 Jun 24;11(13):3649. doi: 10.3390/jcm11133649.
1Department of General Surgery and Surgical Specialties 'Paride Stefanini', Sapienza University of Rome, 00161 Rome, Italy.
2Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, 80138 Naples, Italy.
3Gastroenterology and Endoscopy Unit, AORN San Giuseppe Moscati, 83100 Avellino, Italy.
4Department of Surgery Pietro Valdoni, Sapienza University of Rome, 00161 Rome, Italy.
5Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome's extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between genetic, nutritional, and environmental factors, creating a complex network of yet-unclarified pathogenetic mechanisms in which the role of insulin resistance (IR) could be crucial. This review detailed the clinical and pathogenetic evidence involved in the NAFLD-IR relationship, presenting both the classic and more innovative models. In particular, we focused on the reciprocal effects of IR, oxidative stress, and systemic inflammation on insulin-sensitivity disruption in critical regions such as the hepatic and the adipose tissue, while considering the impact of genetics/epigenetics on the regulation of IR mechanisms as well as nutrients on specific insulin-related gene expression (nutrigenetics and nutrigenomics). In addition, we discussed the emerging capability of the gut microbiota to interfere with physiological signaling of the hormonal pathways responsible for maintaining metabolic homeostasis and by inducing an abnormal activation of the immune system. The translation of these novel findings into clinical practice could promote the expansion of accurate diagnostic/prognostic stratification tools and tailored pharmacological approaches.