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A Metal-Free, Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells

Role of Insulin Resistance in MAFLD

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Department of Clinical Nutrition Therapy, The University of Tokyo, Tokyo 113-8655, Japan
Clinical Nutrition Program, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan
Toranomon Hospital, Tokyo 105-8470, Japan
Authors to whom correspondence should be addressed.
Academic Editor: Yoshio Sumida
Int. J. Mol. Sci. 2021, 22(8), 4156;
Received: 7 April 2021 / Accepted: 14 April 2021 / Published: 16 April 2021
(This article belongs to the Special Issue Metabolic Associated Fatty Liver Disease: A New Definition)
Many studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying the development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). Metabolic dysfunction in this context encompasses obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, with insulin resistance as the common underlying pathophysiology. Imbalance between energy intake and expenditure results in insulin resistance in various tissues and alteration of the gut microbiota, resulting in fat accumulation in the liver. The role of genetics has also been revealed in hepatic fat accumulation and fibrosis. In the process of fat accumulation in the liver, intracellular damage as well as hepatic insulin resistance further potentiates inflammation, fibrosis, and carcinogenesis. Increased lipogenic substrate supply from other tissues, hepatic zonation of Irs1, and other factors, including ER stress, play crucial roles in increased hepatic de novo lipogenesis in MAFLD with hepatic insulin resistance. Herein, we provide an overview of the factors contributing to and the role of systemic and local insulin resistance in the development and progression of MAFLD. View Full-Text
Keywords: NAFLD; MAFLD; insulin signaling; insulin resistance; de novo lipogenesis (DNL); triglycerides (TG); diacylglycerol (DAG); lipid metabolism NAFLD; MAFLD; insulin signaling; insulin resistance; de novo lipogenesis (DNL); triglycerides (TG); diacylglycerol (DAG); lipid metabolism
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MDPI and ACS Style

Sakurai, Y.; Kubota, N.; Yamauchi, T.; Kadowaki, T. Role of Insulin Resistance in MAFLD. Int. J. Mol. Sci. 2021, 22, 4156.

AMA Style

Sakurai Y, Kubota N, Yamauchi T, Kadowaki T. Role of Insulin Resistance in MAFLD. International Journal of Molecular Sciences. 2021; 22(8):4156.

Chicago/Turabian Style

Sakurai, Yoshitaka, Naoto Kubota, Toshimasa Yamauchi, and Takashi Kadowaki. 2021. "Role of Insulin Resistance in MAFLD" International Journal of Molecular Sciences 22, no. 8: 4156.

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