Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease

Cazanave, Sophie C.; Sanyal, Arun J.

doi:10.1007/978-3-319-25065-6_5

Cited by 4 publications

(3 citation statements)

References 149 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, the body composition alteration with the highest prevalence in the population was the elevated body fat percentage, with 49.04% of young people experiencing the alteration (Figure 1A). This may be worrying because one of the main causes of obesity comorbidities is lipotoxicity or ectopic fat accumulation [27][28][29]. According to Murguía-Romero (2013) [17], the prevalence of elevated insulin found in a sample of young Mexicans was 9.5% in women and 12.4% in men, and in the case of high HOMA-IR, it was found to be 12.1% in women and 15.3% in men.…”

Section: Discussionmentioning

confidence: 99%

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

et al. 2020

View full text Add to dashboard Cite

The elongation of very long chain fatty acids (ELOVL) is a family of seven enzymes that have specific functions in the synthesis of fatty acids. Some have been shown to be related to insulin secretion (ELOVL2), and in the lipid profile (ELOVL6) and patients with various pathologies. The present work focused on the study of ELOVL polymorphs with clinical markers of non-communicable chronic diseases in the Mexican population. A sample of 1075 participants was obtained, who underwent clinical, biochemical, and nutritional evaluation, and a genetic evaluation of 91 genetic variants of ELOVL was considered (2–7). The results indicate a 33.16% prevalence of obesity by body mass index, 13.84% prevalence of insulin resistance by homeostatic model assessment (HOMA) index, 7.85% prevalence of high cholesterol, and 20.37% prevalence of hypercholesterolemia. The deprived alleles showed that there is no association between them and clinical disease risk markers, and the notable finding of the association studies is that the ELOVL2 variants are exclusive in men and ELVOL7 in women. There is also a strong association of ELOVL6 with various markers. The present study shows, for the first time, the association between the different ELOVLs and clinical markers of chronic non-communicable diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This results in increased lipid levels in circulation that potentially contribute to cardiovascular disease. Furthermore, dyslipidemia can result in increased inflammation that could result in development of cirrhosis [10][11][12]. In the lung, collagen production is increased in addition to the increase in the levels of inflammatory cytokines, suggesting the potential development of fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma [13][14].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers

2017

View full text Add to dashboard Cite

Third-hand smoke (THS) is a newly discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces where smoking has occurred. Our objective was to determine whether there is a time-dependent effect of THS exposure on health. Using an in vivo exposure mouse system that mimics exposure of humans to THS, we investigated its effects on biomarkers found in serum, and in liver and brain tissues. Mice were exposed to THS for 1, 2, 4, or 6 months and brain, liver, and serum were collected. We found that THS exposure, as early as 1 month, resulted in increased circulating inflammatory cytokines, tumor necrosis factor by an order of magnitude of 2 and granulocyte macrophage colony-stimulating factor by an order of magnitude of 1.5 and in increases in the stress hormone epinephrine and the liver damage biomarker aspartate aminotransferase (AST), increased in magnitude 1.5 and 2.5 times compared with controls, respectively. THS exposure for 2 months resulted in further damage and at 4 and 6 months, many factors related to oxidative stress were altered and caused molecular damage. We also found that the mice became hyperglycemic and hyperinsulinimic suggesting that insulin resistance (IR) may be a significant consequence of long-term exposure to THS. In conclusion, time-dependent THS exposure has a significant effect on health as early as 1 month after initiation of exposure and these alterations progressively worsen with time. Our studies are important because virtually nothing is known about the effects of increased THS exposure time, they can serve to educate the public on the dangers of THS, and the biomarkers we identified can be used in the clinic, once verified in exposed humans.

show abstract

“…NAFLD is not limited to adults; the incidence of NAFLD among the pediatric population is increasing and it is estimated to account for about 14% of all NAFLD cases [25,26]. NAFLD is a complex process that results from metabolic abnormalities [27,28]. Many patients show dyslipidemia, malfunction of beta oxidative enzymes, deficiency in lipoproteins, and immune dysregulation [29,30].…”

Section: Introductionmentioning

confidence: 99%

THS Toxins Induce Hepatic Steatosis by Altering Oxidative Stress and SIRT1 Levels

Flores¹,

Adhami²,

Martins‐Green³

2016

J Clinic Toxicol

View full text Add to dashboard Cite

Background: Third hand smoke (THS) forms when second hand smoke (SHS) tobacco toxins accumulate on surfaces such as walls, carpets and clothing and can result in adverse health effects. Objective: This study was designed to investigate the mechanism of THS-induced hepatic steatosis. Methodology: We used an in vivo exposure system that mimics exposure of humans to THS to investigate the effects of THS on hepatic lipid metabolism. THS-exposed mice were treated either with the liver-damaging drug, Nacetyl-p-aminophenol (APAP/Tylenol) to increase oxidative stress or with the antioxidants N-acetyl-cysteine and α-Tocopherol which decrease oxidative stress. Results: THS-exposed mice have higher levels of superoxide dismutase activity and H 2 O 2 levels. However, no significant changes in activity of the antioxidant enzymes catalase and glutathione peroxidase were found, implying the presence of high levels of hydrogen peroxide in the liver. Furthermore, THS-exposed mice also have a lower NADP+/NADPH ratio, indicating decreased ability of these mice to combat oxidative stress. THS-exposed mice show a decrease in ATP production, increase in aspartate aminotransferase (AST) activity, as well as increased molecular damage (lipid peroxidation, protein nitrosylation and DNA damage). Treating THS-exposed mice with APAP/Tylenol enhances the THS-induced damage whereas treating with antioxidants reduces the damage. THSexposed mice also have lower sirtuin 1 (SIRT1) levels compared to controls which decreased activation of 5' AMPactivated protein kinase (AMPK) and increased sterol regulatory element binding protein 1c (SREBP1c). Conclusion: THS-exposed mice on a normal diet have increased oxidative stress and damage mediated by oxidative stress, which results in alterations to the SIRT1/AMPK/SREPB1c signaling pathway. Increasing oxidative stress results in enhanced THS-induced damage whereas decreasing oxidative stress causes improvement in the THS-induced liver damage. Our results show that THS is a new risk factor contributing to the development of liver steatosis and highlight the danger of THS in general.

show abstract

Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease

Cited by 4 publications

References 149 publications

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers

THS Toxins Induce Hepatic Steatosis by Altering Oxidative Stress and SIRT1 Levels

Contact Info

Product

Resources

About