Non-alcoholic fatty liver disease: a metabolic burden promoting atherosclerosis

2020 ◽  
Vol 134 (13) ◽  
pp. 1775-1799 ◽  
Author(s):  
Lei Zhang ◽  
Zhi-Gang She ◽  
Hongliang Li ◽  
Xiao-Jing Zhang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cell Activation ◽  
Cell Damage ◽  
Alcoholic Fatty Liver ◽  
Drug Candidates ◽  
Metabolic Burden ◽  
Molecular Events ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) has become the fastest growing chronic liver disease, with a prevalence of up to 25% worldwide. Individuals with NAFLD have a high risk of disease progression to cirrhosis, hepatocellular carcinoma (HCC), and liver failure. With the exception of intrahepatic burden, cardiovascular disease (CVD) and especially atherosclerosis (AS) are common complications of NAFLD. Furthermore, CVD is a major cause of death in NAFLD patients. Additionally, AS is a metabolic disorder highly associated with NAFLD, and individual NAFLD pathologies can greatly increase the risk of AS. It is increasingly clear that AS-associated endothelial cell damage, inflammatory cell activation, and smooth muscle cell proliferation are extensively impacted by NAFLD-induced systematic dyslipidemia, inflammation, oxidative stress, the production of hepatokines, and coagulations. In clinical trials, drug candidates for NAFLD management have displayed promising effects for the treatment of AS. In this review, we summarize the key molecular events and cellular factors contributing to the metabolic burden induced by NAFLD on AS, and discuss therapeutic strategies for the improvement of AS in individuals with NAFLD.

scholarly journals Mathematical Modeling of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD)

2020 ◽  
Author(s):  
Hermann-Georg Holzhütter ◽  
Nikolaus Berndt
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cell Damage ◽  
Generic Model ◽  
Large Individual ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

SummaryNon-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations. Here we present a generic model of free fatty acid (FFA)-induced NAFLD that constitutes the liver as ensemble of small liver units (LUs) differing in their vulnerability to toxic FFAs and capacities to metabolize FFAs and repair FFA-induced cell damage. The model describes NAFLD as cascading liver failure where failure of few LUs increases the risk for other LUs to fail as well. Model simulations provided the following insights: (1) The large individual differences in the final outcome of NAFLD are already predetermined by the random intra-hepatic heterogeneity of functional capacities; (2) NAFLD amplifies the deleterious impact of secondary damaging although such hits are not necessary for continuous disease worsening; (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.

scholarly journals Computational Hypothesis: How Intra-Hepatic Functional Heterogeneity May Influence the Cascading Progression of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD)

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 578
Author(s):  
Hermann-Georg Holzhütter ◽  
Nikolaus Berndt
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cell Damage ◽  
High Plasma ◽  
Alcoholic Fatty Liver ◽  
Liver Model ◽  
Developed Nations ◽  
Functional Capacities ◽  
Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations, affecting around 25% of the population. Elucidating the factors causing NAFLD in individual patients to progress in different rates and to different degrees of severity, is a matter of active medical research. Here, we aim to provide evidence that the intra-hepatic heterogeneity of rheological, metabolic and tissue-regenerating capacities plays a central role in disease progression. We developed a generic mathematical model that constitutes the liver as ensemble of small liver units differing in their capacities to metabolize potentially cytotoxic free fatty acids (FFAs) and to repair FFA-induced cell damage. Transition from simple steatosis to more severe forms of NAFLD is described as self-amplifying process of cascading liver failure, which, to stop, depends essentially on the distribution of functional capacities across the liver. Model simulations provided the following insights: (1) A persistently high plasma level of FFAs is sufficient to drive the liver through different stages of NAFLD; (2) Presence of NAFLD amplifies the deleterious impact of additional tissue-damaging hits; and (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.

Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

2020 ◽  
pp. 1-8
Author(s):  
Jeniffer Danielle M. Dutra ◽  
Quelson Coelho Lisboa ◽  
Silvia Marinho Ferolla ◽  
Carolina Martinelli M. L. Carvalho ◽  
Camila Costa M. Mendes ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Disease ◽  
Fatty Liver ◽  
Disease Severity ◽  
Fatty Liver Disease ◽  
Hypovitaminosis D ◽  
Alcoholic Fatty Liver ◽  
Vitamin D Levels ◽  
The Mean ◽  
Alcoholic Fatty Liver Disease

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

Non-Alcoholic Fatty Liver Disease in Overweight Children and its Relationship with Retinol Serum Levels

2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Fatty Liver Disease ◽  
Thiobarbituric Acid ◽  
Serum Levels ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.

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