Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Lim, Soo; Taskinen, Marja‐Riitta; Borén, Jan

doi:10.1111/obr.12820

Cited by 72 publications

(64 citation statements)

References 170 publications

(179 reference statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

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confidence: 99%

“…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.…”

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confidence: 99%

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

Yang

Cai

et al. 2019

Phytotherapy Research

185

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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

Yang

Cai

et al. 2019

Phytotherapy Research

185

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“…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 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Aims Epidemiological studies have correlated cardiovascular disease and atherosclerosis with lifestyle factors such as sedentary behaviour and a high‐calorie diet. Recent studies of pathogenesis have highlighted the significance of the intestinal microbiota and chronic inflammation with respect to both the onset and development of atherosclerosis. This study examined the hypothesis that the oral administration of quercetin to low‐density lipoprotein receptor‐null (Ldlr−/−) mice would improve gut health by altering the gut microbiota and controlling the levels of atherogenic lipid metabolites and proinflammatory mediators in the intestine and serum. Methods and Results Mice were maintained on a high‐fat diet with or without oral quercetin administration for 12 weeks. Quercetin treatment suppressed body weight gains and reduced the extent of atherosclerotic lesions in the aortic sinus. Reduced malondialdehyde and increased interleukin 6 levels further indicated the protective effect of quercetin against immune/inflammatory responses and oxidative stress. Furthermore, quercetin led to decreased intestinal levels of cholesterol, lysophosphatidic acids and atherogenic lysophosphatidylcholine (LPC 18:1) and an increased level of coprostanol. A phylum‐level microbial analysis revealed that quercetin treatment reduced the abundance of Verrocomicrobia and increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria and Firmicutes. A Spearman analysis revealed negative correlations of Actinobacteria with intestinal and plasma LPC 18:1 and caecal cholesterol levels and of Firmicutes and Cyanobacteria with the plasma LPC 18:1 level. Conclusions This study demonstrated the ability of quercetin treatment to reduce lipid levels, as well as the areas of atherosclerotic lesions and sizes of plaques. This treatment also altered the composition of the gut microbiota and decreased the levels of atherogenic lipid metabolites. Significance and Impact of the Study Oral quercetin treatment may represent a new approach to mitigating the onset and development of atherosclerosis.

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“…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.…”

Section: Nafld Obesity and Ao In South Koreamentioning

confidence: 99%

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

Son¹,

Park²,

Lee³

et al. 2020

Preprint

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Background Obese nonalcoholic fatty liver disease (NAFLD) is closely associated with an increased risk of cardiovascular disease (CVD). However, the association between non-obese NAFLD and the incidence of CVD is still unclear and little is known about deleterious factors related to their inter-relationship. Here, we investigated the effects of abdominal obesity (AO) and/or NAFLD on CVD risk.Methods We enrolled 8,422 patients who did not have CVD or consume excessive amounts of alcohol at baseline from the Korean Genome and Epidemiology Study (KoGES). NAFLD was defined using the Fatty Liver Index (FLI). Obesity was defined as a body mass index (BMI) ≥25 kg/m2, and AO was defined as a waist circumference (WC) ≥90 cm in men and ≥85 cm in women. Subjects were sub-divided into eight groups depending on whether they were obese, AO, and/or NAFLD.Results In the full cohort, during a median 11.6 years of follow-up period, the incidence rate (IR) of CVD was 8.07%. The IR of CVD in participants with NAFLD was 1.9-fold higher than in those without NAFLD. The IR per 1,000 person-years for CVD was highest in the non-obese abdominal obesity subjects with NAFLD (15.76 [95% confidence interval (CI), 11.76–20.69]). Compared with participants who did not have obesity, AO, or NAFLD, the adjusted hazard ratio for CVD was 1.67 (95% CI: 1.16–2.41) in non-obese NAFLD patients with AO, 1.60 (95% CI: 1.21–2.11) in NAFLD patients with obesity and AO, and 0.54 (95% CI: 0.32–0.91) in obese subjects without either NAFLD or AO.Conclusions The co-occurrence of AO with NAFLD appears to be strongly associated with an increased risk of CVD regardless of obesity; but its risk is higher in non-obese subjects. By contrast, obese individuals without AO or NAFLD appear to be at lower risk. Therefore, early prevention and control of AO and NAFLD is an important means of reducing the risk of CVD, even in subjects with a normal BMI.

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Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Cited by 72 publications

References 170 publications

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

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

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

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

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