Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low-grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue and de novo lipogenesis can lead to NAFLD and insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidaemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is a phenotype of cardiometabolic syndrome. Notably, researchers have discovered a close association between NAFLD and impaired glucose metabolism and focused on the role of NAFLD in the development of type 2 diabetes. Moreover, recent studies provide substantial evidence for an association between NAFLD and atherosclerosis and cardiometabolic disorders. Even if NAFLD can progress into severe liver disorders including nonalcoholic steatohepatitis (NASH) and cirrhosis, the majority of subjects with NAFLD die from cardiovascular disease eventually. In this review, we propose a potential pathological link between NAFLD/NASH and cardiometabolic syndrome. The potential factors that can play a pivotal role in this link, such as inflammation, insulin resistance, alteration in lipid metabolism, oxidative stress, genetic predisposition, and gut microbiota are discussed. KEYWORDS cardiometabolic syndrome, nonalcoholic fatty liver disease, inflammation, oxidative stress 1 | INTRODUCTION | Prevalence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH)NAFLD covers a spectrum of diseases ranging from simple steatosis to NASH, which is distinguished from the former by the presence of progressive hepatic fibrosis. 1,2 The prevalence of NAFLD or NASH in the general population varies according to the diagnostic criteria and tools used to stage the condition. 3,4 In the United States, liver biopsies performed on potential liver donors revealed that 20% of donors were ineligible for organ donation because of a high degree of steatosis (>30%). 5 A study in which liver biopsies were performed on 589 consecutive potential liver-transplant donors found an NAFLD prevalence of 51%. 6 A series of autopsies showed a broad range in the prevalence of NAFLD. The prevalence of NASH in autopsy cases of lean Abbreviations: ALT, alanine aminotransferase; apoB, apolipoprotein-B; AST, aspartate aminotransferase; ChREBP, carbohydrate-responsive element-binding protein; CV, cardiovascular; ER, endoplasmic reticulum; FFA, free fatty acid; FIAF, fasting-induced adipocyte factor; GSK-3β, glycogen synthase kinase-3β; IL-6, interleukin-6; IRS1, insulin receptor substrate-1

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

“…Nonalcoholic fatty liver disease (NAFLD) is the main complication of Type 2 diabetes (T2DM)‐related liver disease and is closely related to obesity and metabolic syndrome (Goedeke, Perry, & Shulman, ; Lim, Taskinen, & Boren, ; Mantovani, Byrne, & Bonora, ). More pronounced insulin resistance and hyperglycemia can be observed in T2DM combined with NAFLD patients, who also have higher cardiovascular and cerebrovascular disease suffering rate (Lim et al, ; Moh Moh et al, ; Vanjiappan, Hamide, Ananthakrishnan, Periyasamy, & Mehalingam, ). Caused by insulin resistance, lipid accumulation will promote the development of NAFLD in T2DM patients.…”

“…Young & Middle-aged Teachers and Presidents; Key Natural Science Foundation of Jiangsu Higher Education Institutions of China, Grant/Award Numbers: 19KJA460008 and 15KJA310005; "333" Foundation of Jiangsu Province, Grant/Award Number: BRA2015329; Qing Lan project 1 | INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is the main complication of Type 2 diabetes (T2DM)-related liver disease and is closely related to obesity and metabolic syndrome (Goedeke, Perry, & Shulman, 2019;Lim, Taskinen, & Boren, 2018;Mantovani, Byrne, & Bonora, 2018).…”

“…More pronounced insulin resistance and hyperglycemia can be observed in T2DM combined with NAFLD patients, who also have higher cardiovascular and cerebrovascular disease suffering rate (Lim et al, 2018;Moh Moh et al, 2018;Vanjiappan, Hamide, Ananthakrishnan, Periyasamy, & Mehalingam, 2018). Caused by insulin resistance, lipid accumulation will promote the development of NAFLD in T2DM patients.…”

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites

“…Recent studies of pathogenesis have also highlighted the significant roles of the intestinal microbiota and chronic inflammation in both the onset and development of atherosclerosis (Paccou et al ; Robles‐Vera et al ; Lim et al ). Although the Bacteroidetes and Firmicutes phyla dominate the gut microbiomes of humans and numerous other vertebrate species (Xue et al ; Alrubaye et al ), small populations of Actinobacteria, Cyanobacteria and Fusobacteria also contribute to a multifaceted microbial community (Ding et al ; Ma et al ).…”

Nonalcoholic Fatty Liver Disease in Non-Obese Subjects With Abdominal Obesity is Associated With A Higher Risk of Advanced Cardiovascular Disease: A 14 Year Prospective Cohort Study

“…Relationships between NAFLD, obesity, and AO, and cardiovascular risk NAFLD is a chronic disease that is characterized by fat accumulation and in ammation in the liver; therefore, individuals who are obese and/or have AO are at the greatest risk of developing NAFLD. In addition, the majority of NAFLD patients die from cardiovascular disease (33). Obesity is generally de ned as a state of abnormal or excessive accumulation of adipose tissue, which predisposes to a variety of health problems that are associated with cardio-metabolic abnormalities.…”