Mechanisms Linking Metabolic-Associated Fatty Liver Disease (MAFLD) to Cardiovascular Disease

Badmus, Olufunto O.; Hinds, Terry D.; Stec, David E.

doi:10.1007/s11906-023-01242-8

Cited by 13 publications

(11 citation statements)

References 114 publications

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“…Additionally, our research showed that individuals with MAFLD had significantly elevated SBP and DBP values across all ethnic groups. The conditions of hypertension and MAFLD share common metabolic disruptions, such as insulin resistance, dyslipidemia, obesity, and inflammation due to fatty liver, which may contribute to their mutual reinforcement [28][29][30]. Epidemiological studies have demonstrated that hypertension is prevalent in up to 40% of patients with MAFLD [31].…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological studies have demonstrated that hypertension is prevalent in up to 40% of patients with MAFLD [31]. Furthermore, MAFLD is linked to increased susceptibility to various other cardiovascular conditions [30,32]. Therefore, potential pharmacotherapies for MAFLD include statins, lipid-lowering agents, hypoglycemic medications, antihypertensive compounds, and antioxidant intervention [33].…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in Demographic Characteristics, Physical Indices and Lifestyle Conditions

Ye,

Wang,

Shi

et al. 2024

Preprint

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Background and Aims: The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is high among U.S. adults, but studies on its occurrence in different ethnic and age groups are limited. The aim of the present study was to assess MAFLD occurrence among the United States (U.S.) adults by considering demographic characteristics, physical indices, and lifestyle conditions. Methods: This study utilized the National Health and Nutrition Examination Survey (NHANES) data 2009-2018 from 23,546 participants aged ≥20 years. Variables such as age, sex, race, body mass index (BMI), waist circumference (WC), blood pressure, sedentary behavior, sleep, and depression were analyzed. Results: Among 9933 participants, 3562 had MAFLD (34.1%), with notably higher percentages of Mexican-Americans (54.1%) and lower percentages of blacks (20.5%). The incidence of MAFLD was significantly greater (P<0.001) in males (39%) than in females (29.2%), which was particularly evident within the 36-40 years age group. The MAFLD incidence exhibited an age-dependent pattern, initially increasing and subsequently declining (except for whites). Compared to white MAFLD patients, black MAFLD patients exhibited greater BMI, WC, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values, whereas values for these measures were lower among Mexican-American patients. Logistic regression analysis adjusting for age and sex revealed that depression was more common among MAFLD patients (P<0.001), except for severe depression (P>0.05). Notably, the MAFLD incidence was not significantly associated with sedentary behavior or sleep duration. Conclusions: The MAFLD incidence varies across different racial, age, and sex groups, and targeted interventions are essential for reducing the burden of MAFLD. However, further research is necessary to explore the correlations among MAFLD incidence, sleep patterns, and an inactive lifestyle.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in Demographic Characteristics, Physical Indices and Lifestyle Conditions

Ye,

Wang,

Shi

et al. 2024

Preprint

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“…Cardiovascular disease (CVD) remains a serious complication of nonalcoholic fatty liver disease (NAFLD) accounting for more than 40% of mortality in NAFLD patients 1 . NAFLD is associated with increased risk of coronary artery disease, heart failure, and valvular dysfunction 2 . The exact mechanism by which NAFLD drives CVD is not fully understood given that NAFLD is often coupled with obesity, insulin resistance, and dyslipidemia; so that the contribution of NAFLD to CVD is confounded by these accompanying risk factors.…”

Section: Introductionmentioning

confidence: 99%

“… 1 NAFLD is associated with increased risk of coronary artery disease, heart failure, and valvular dysfunction. 2 The exact mechanism by which NAFLD drives CVD is not fully understood given that NAFLD is often coupled with obesity, insulin resistance, and dyslipidemia; so that the contribution of NAFLD to CVD is confounded by these accompanying risk factors. In addition, due to the importance of increased incidence of hepatic steatosis associated with obesity and metabolic syndrome, a new nomenclature of metabolic dysfunction‐associated steatotic liver disease (MASLD) was recently adopted.…”

Section: Introductionmentioning

confidence: 99%

Cardiac lipotoxicity and fibrosis underlie impaired contractility in a mouse model of metabolic dysfunction‐associated steatotic liver disease

Badmus,

da Silva,

et al. 2024

FASEB BioAdvances

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The leading cause of death among patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) is cardiovascular disease. A significant percentage of MASLD patients develop heart failure driven by functional and structural alterations in the heart. Previously, we observed cardiac dysfunction in hepatocyte‐specific peroxisome proliferator‐activated receptor alpha knockout (PparaHepKO), a mouse model that exhibits hepatic steatosis independent of obesity and insulin resistance. The goal of the present study was to determine mechanisms that underlie hepatic steatosis‐induced cardiac dysfunction in PparaHepKO mice. Experiments were performed in 30‐week‐old PparaHepKO and littermate control mice fed regular chow. We observed decreased cardiomyocyte contractility (0.17 ± 0.02 vs. 0.24 ± 0.02 μm, p < 0.05), increased cardiac triglyceride content (0.96 ± 0.13 vs. 0.68 ± 0.06 mM, p < 0.05), collagen type 1 (4.65 ± 0.25 vs. 0.31 ± 0.01 AU, p < 0.001), and collagen type 3 deposition (1.32 ± 0.46 vs. 0.05 ± 0.03 AU, p < 0.05). These changes were associated with increased apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (30.9 ± 4.7 vs. 13.1 ± 0.8%, p < 0.006) and western blots showing increased cleaved caspase‐3 (0.27 ± 0.006 vs. 0.08 ± 0.01 AU, p < 0.003) and pro‐caspase‐3 (5.4 ± 1.5 vs. 0.5 ± 0.3 AU, p < 0.02), B‐cell lymphoma protein 2‐associated X (0.68 ± 0.07 vs. 0.04 ± 0.04 AU, p < 0.001), and reduced B‐cell lymphoma protein 2 (0.29 ± 0.01 vs. 1.47 ± 0.54 AU, p < 0.05). We further observed elevated circulating natriuretic peptides and exercise intolerance in PparaHepKO mice when compared to controls. Our data demonstrated that lipotoxicity, and fibrosis underlie cardiac dysfunction in MASLD.

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“…In MAFLD hepatocytes produce and release a number of chemical compounds that create an atherogenic environment, hypertension and increased blood clotting. Moreover, premature and increased cardiovascular mortality is observed in patients with MAFLD [2,12].…”

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confidence: 99%

Manifestations of Liver Impairment and the Effects of MH-76, a Non-Quinazoline α1-Adrenoceptor Antagonist, and Prazosin on Liver Tissue in Fructose-Induced Metabolic Syndrome

Kubacka,

Nowak,

Zadrożna

et al. 2023

Metabolites

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Excessive fructose consumption may lead to metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD) and hypertension. α1-adrenoceptors antagonists are antihypertensive agents that exert mild beneficial effects on the metabolic profile in hypertensive patients. However, they are no longer used as a first-line therapy for hypertension based on Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) outcomes. Later studies have shown that quinazoline-based α1-adrenolytics (prazosin, doxazosin) induce apoptosis; however, this effect was independent of α1-adrenoceptor blockade and was associated with the presence of quinazoline moiety. Recent studies showed that α1-adrenoceptors antagonists may reduce mortality in COVID-19 patients due to anti-inflammatory properties. MH-76 (1-[3-(2,6-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride)) is a non-quinazoline α1-adrenoceptor antagonist which, in fructose-fed rats, exerted anti-inflammatory, antihypertensive properties and reduced insulin resistance and visceral adiposity. In this study, we aimed to evaluate the effect of fructose consumption and treatment with α1-adrenoceptor antagonists of different classes (MH-76 and prazosin) on liver tissue of fructose-fed rats. Livers were collected from four groups (Control, Fructose, Fructose + MH-76 and Fructose + Prazosin) and subjected to biochemical and histopathological studies. Both α1-adrenolytics reduced macrovesicular steatosis and triglycerides content of liver tissue and improved its antioxidant capacity. Treatment with MH-76, contrary to prazosin, reduced leucocytes infiltration as well as decreased elevated IL-6 and leptin concentrations. Moreover, the MH-76 hepatotoxicity in hepatoma HepG2 cells was less than that of prazosin. The use of α1-adrenolytics with anti-inflammatory properties may be an interesting option for treatment of hypertension with metabolic complications.

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Mechanisms Linking Metabolic-Associated Fatty Liver Disease (MAFLD) to Cardiovascular Disease

Cited by 13 publications

References 114 publications

Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in Demographic Characteristics, Physical Indices and Lifestyle Conditions

Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in Demographic Characteristics, Physical Indices and Lifestyle Conditions

Cardiac lipotoxicity and fibrosis underlie impaired contractility in a mouse model of metabolic dysfunction‐associated steatotic liver disease

Manifestations of Liver Impairment and the Effects of MH-76, a Non-Quinazoline α1-Adrenoceptor Antagonist, and Prazosin on Liver Tissue in Fructose-Induced Metabolic Syndrome

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