The Cardiovascular Link to Nonalcoholic Fatty Liver Disease

Pacana, Tommy; Fuchs, Michael

doi:10.1016/j.cld.2012.05.008

Cited by 29 publications

(17 citation statements)

References 79 publications

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“…Currently, some studies reveal that NAFLD is closely related to the increased risk of cardiovascular disease (17). In NAFLD patients, severe insulin resistance, sustained hyperinsulinism, disordered lipid metabolism (increase in TG, reduction in HDL-C, and elevation in LDL-C) and subclinical inflammatory state may serve as risk factors to promote the occurrence and development of atherosclerosis (17,18). On the other hand, NAFLD may result in progressive hepatitis, hepatic fibrosis or cirrhosis, or even liver failure (19).…”

Section: Discussionmentioning

confidence: 99%

Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease

Fan¹,

Qin²,

Xu³

et al. 2013

Arq Bras Endocrinol Metab

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Objective: To investigate the effects of exenatide on blood glucose, body weight and hepatic enzymes in patients with type 2 diabetes mellitus (T2DM) and concomitant non-alcoholic fatty liver disease (NAFLD). Subjects and methods: One hundred and seventeen patients with T2DM and NAFLD were randomly divided into exenatide group and metformin group. Patients were treated with exenatide and metformin, respectively, for 12 weeks. Results: After 12 weeks of treatment, body weight, body mass index (BMI), waist-to-hip ratio, HbA1c, FPG, 2-h PPG, ALT, AST, γ-GT, and hs-CRP were significantly reduced, and the AST/ALT ratio and adiponectin were markedly increased in both groups. BMI, waist-to-hip ratio, 2-h PPG, ALT, AST, γ-GT, and hs-CRP were markedly lower, and AST/ ALT ratio and adiponectin in the exenatide group were dramatically higher than in the metformin group. Conclusion: Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD. Arq Bras Endocrinol Metab. 2013;57(9):702-8 Keywords Exenatide; metformin; non-alcoholic fatty liver disease; type 2 diabetes mellitus RESUMO Objetivo: Investigar os efeitos do exenatide sobre a glicose sérica, peso corporal e enzimas hepá-ticas em pacientes com diabetes melito tipo 2 (T2DM) e doença hepática gordurosa não alcoólica (DHGNA). Sujeitos e métodos: Um total de 117 pacientes com T2DM e DHGNA foi aleatoriamente separado em dois grupos, um tratado com exenatide e um tratado com metformina. Os pacientes foram tratados por 12 semanas. Resultados: Após 12 semanas de tratamento, o peso corporal, índice de massa corporal (IMC), relação cintura-quadril, HbA1c, FPG, glicose pós-prandial, ALT, AST, γ-GT e proteína C-reativa foram significativamente reduzidos, e a relação AST/ALT e a adiponectina aumentaram marcadamente nos dois grupos. O IMC, relação cintura-quadril, glicose pós-prandial, ALT, AST, γ-GT e proteína C-reativa foram marcadamente menores, e a relação AST/ALT e a adiponectina foram dramaticamente mais altas no grupo tratado com exenatide do que no grupo tratado com metformina. Conclusão: Comparado com a metformina, o exenatide controla melhor a glicose sérica, reduz o peso corporal e melhora as enzimas hepáticas, atenuando a DHGNA em pacientes com T2DM de ocorrência concomitante com a DHGNA. Arq Bras Endocrinol Metab. 2013;57(9):702-8 Descritores Exenatide; metformina; doença hepática gordurosa não alcoólica; diabetes melito tipo 2

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Section: Discussionmentioning

confidence: 99%

Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease

Fan¹,

Qin²,

Xu³

et al. 2013

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

show abstract

“…20 Increasing evidence of different clinical trials shows that NAFLD is a risk factor for cardiovascular disease. 21 To gain insights into the molecular events underlying the association between NAFLD and cardiovascular disease, it is essential to establish and analyze murine models capable of portraying and translating the human pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis

Kampschulte

Stöckl

Langheinrich

et al. 2014

Laboratory Investigation

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Nonalcoholic fatty liver disease has been linked to cardiovascular diseases and atherosclerosis. The aim of the current study was to characterize the hepatic pathology leading to fibrosis and tumors in a murine model of atherosclerosis.Male apolipoprotein E/low-density lipoprotein receptor double-knockout mice (AL) mice were fed with a high fat and high cholesterol western diet for 35 weeks (AL mice on WD). Protein and mRNA analysis as well as micro-computed tomography (micro-CT) were performed to assess oxidative stress, liver damage, inflammation, fibrosis, signaling pathways, vascularization, and tumorigenesis. Controls were chosen to distinguish between genetically and dietary effects in steatohepatitis and associated tumorigenesis. Hepatic inflammation and dyslipidemia were increased in AL mice on WD compared with wild-type mice on WD. Uniquely, AL mice on WD showed a spontaneous development of tumors (30% of cases) and thickening of intrahepatic vessel walls. Functionally relevant underlying signaling pathways such as NF-kB, Stat3, JNK, and AKT were differentially regulated between AL and wild-type mice on WD. Micro-CT was capable of visualizing and quantitatively distinguishing tumor neovascularization from vascularization in non-neoplastic liver tissue. AL mice on WD diet represent a novel model combining atherosclerosis and nonalcoholic fatty liver disease. Signaling pathways of liver cell damage and compensatory liver regeneration in combination with enhanced inflammation appear to be crucial for the spontaneous development of tumors in AL mice on WD. Micro-CT represents a new and powerful technique for the ultrastructural and three-dimensional assessment of the vascular architecture of liver tumors.

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“…16 From the clinical perspective, using nutrients to decrease hepatic lipid content can partially inhibit atherosclerotic lesion development. Our findings are consistent with prior data from human and animal studies to suggest that fish oil supplement can minimize the development of NAFLD and liver fat accumulation, 17 which correlate with lower aortic cholesterol accumulation.…”

Section: Discussionmentioning

confidence: 99%

Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios

Wang

Matthan

et al. 2014

Clinical Nutrition

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Background & aims Diets with low omega (ω)-6 polyunsaturated fatty acids (PUFA) to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) ratios have been shown to decrease aortic cholesterol accumulation and have been suggested to promote weight loss. The involvement of the liver and gonadal adipose tissue (GAT) in mediating these effects is not well understood. LDL receptor null mice were used to assess the effect of an atherogenic diet with different ω-6:EPA+DHA ratios on weight gain, hepatic and GAT lipid accumulation, and their relationship to atherosclerosis. Methods Four groups of mice were fed a high saturated fat and cholesterol diet (HSF ω-6) alone, or with ω-6 PUFA to EPA+DHA ratios up to 1:1 for 32 weeks. Liver and GAT were collected for lipid and gene expression analysis. Results The fatty acid profile of liver and GAT reflected the diets. All diets resulted in similar weight gains. Compared to HSF ω-6 diet, the 1:1 ratio diet resulted in lower hepatic total cholesterol (TC) content. Aortic TC was positively correlated with hepatic and GAT TC and triglyceride. These differences were accompanied by significantly lower expression of CD36, ATP-transporter cassette A1, scavenger receptor B class 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), acetyl-CoA carboxylase alpha, acyl-CoA synthetase long-chain family member 5, and stearoyl-coenzyme A desaturase 1 (SCD1) in GAT, and HMGCR, SCD1 and cytochrome P450 7A1 in liver. Conclusions Dietary ω-6:EPA+DHA ratios did not affect body weight, but lower ω-6:EPA+DHA ratio diets decreased liver lipid accumulation, which possibly contributed to the lower aortic cholesterol accumulation.

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The Cardiovascular Link to Nonalcoholic Fatty Liver Disease

Cited by 29 publications

References 79 publications

Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease

Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis

Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios

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