Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD. Citation of this article: Akhtar DH, Iqbal U, Vazquez-Montesino LM, Dennis BB, Ahmed A. Pathogenesis of insulin resistance and atherogenic dyslipidemia in nonalcoholic fatty liver disease.Abbreviations: DNL, de novo lipogenesis; NAFLD, nonalcoholic fatty liver disease; SIBO, small intestinal bacterial overgrowth.

Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis

“…Dyslipidemia is lipotoxic to cells, leading to and/or aggravating insulin resistance. Its typical manifestation is the increase of TG and free fatty acid (FFA) [44][45][46][47] . Increased FFA is an independent pathogenic factor for insulin resistance and can possibly increase the risk for cardiovascular diseases 48,49 .…”

C-Peptide: A Mediator of the Association Between Serum Uric Acid to Creatinine Ratio and Non-Alcoholic Fatty Liver Disease in a Chinese Population With Normal Serum Uric Acid Levels

“…SUA could induce endothelial dysfunction and inhibit nitric oxide bioavailability, which is involved in insulin resistance (31). Thus, higher AUC CP may represent higher endogenous insulin secretion and may be a compensatory of insulin resistance due to higher SUA, namely, higher AUC CP is a sign of insulin resistance, which plays important role in the progress of NAFLD (32). In other hand, many metabolic regulators such as follistatin and fibroblast growth factor (FGF21) were regulated by islet hormone (33,34).…”

Diet‐induced rodent models of obesity‐related metabolic disorders—A guide to a translational perspective

“…[19][20][21] Apart from few cases where the aforesaid disorders evolve without major body weight (BW) changes, obesity strongly exacerbates common pathophysiological traits involving insulin resistance, hyperglycaemia and dyslipidaemia. [22][23][24] For instance, excess circulating free fatty acids (FFA) arising from enlarged adipose tissue may compete with glucose as the substrate in peripheral tissues, fuelling insulin resistance. In addition to impaired glucose uptake by these tissues, increased circulating FFA may also impair pancreatic β-cell function and insulin secretion.…”