scholarly journals Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Dongiovanni ◽  
Stefano Romeo ◽  
Luca Valenti
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Association Studies ◽  
Liver Steatosis ◽  
Liver Fat ◽  
Genome Wide Association Studies ◽  
Very Low Density Lipoproteins ◽  
Fat Accumulation ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Fat

Liver fat accumulation generally related to systemic insulin resistance characterizes nonalcoholic fatty liver disease (NAFLD), which in the presence of nonalcoholic steatohepatitis (NASH) can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease in Western countries. Epidemiological, familial, and twin studies provide evidence for a strong genetic component of NAFLD susceptibility. Recently, genome-wide association studies led to the identification of the major inherited determinants of hepatic fat accumulation:patatin-like phospholipase domain-containing 3 (PNPLA3)I148M gene andtransmembrane 6 superfamily member 2 (TM6SF2)E167K gene variants, involved in lipid droplets remodelling and very low-density lipoproteins secretion, are the major determinants of interindividual differences in liver steatosis, and susceptibility to progressive NASH. In this review, we aimed to provide an overview of recent insights into the genetics of hepatic fat accumulation and steatohepatitis.

scholarly journals Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

2020 ◽  
Vol 11 ◽  
Author(s):  
Terry D. Hinds ◽  
Justin F. Creeden ◽  
Darren M. Gordon ◽  
Donald F. Stec ◽  
Matthew C. Donald ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Fat Utilization ◽  
Hepatic Fat ◽  
Alcoholic Fatty Liver Disease

The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic β-oxidation pathway by increasing PPARα and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone β-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD.

scholarly journals Combined Metabolic Activators Reduces Liver Fat in Nonalcoholic Fatty Liver Disease Patients

2021 ◽  
Author(s):  
Mujdat Zeybel ◽  
Ozlem Altay ◽  
Muhammad Arif ◽  
Xiangyu Li ◽  
Hong Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Animal Experiments ◽  
Liver Fat ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Fat ◽  
Metagenomics Data

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMA) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we observed that CMA can be used develop a pharmacological treatment strategy in NAFLD patients.

scholarly journals Association between diet quality indicators and nonalcoholic fatty liver disease: The FLiO study

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Cristina Galarregui ◽  
M. Angeles Zulet ◽  
Bertha Araceli Marin-Alejandre ◽  
Irene Cantero ◽  
Nora Goodwin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Diet Quality ◽  
Fatty Liver Disease ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Fat

AbstractIntroductionDietary components are contributing factors in the development of Nonalcoholic fatty liver disease (NAFLD). The glycaemic index (GI), glycaemic load (GL) and total antioxidant capacity (TAC) have been considered potential dietary tools influencing diet–disease relationships. The aim of this study was to evaluate associations of the dietary GI, GL, TAC and insulin resistance (IR) condition with hepatic fat in NAFLD adults.Material and methods: 112 overweight/obese adults with NAFLD (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ). Anthropometric, glycemic and lipid profiles, fatty liver quantification by magnetic resonance imaging (MRI) and IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) were assessed at baseline. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193.Results: The median of liver fat content by MRI was 6.4 (3.8–10.9) in the recruited population. Participants with higher liver fat content showed significantly increased values of glucose, insulin, HbA1c and HOMA-IR than those with lower liver fat content (p < 0.05). Correlation analyses revealed relevant positive associations of hepatic fat with GI (r = 0.17; p = 0.077) and GL (r = 0.19; p = 0.047). Also, a negative association between liver fat content and TAC (r = -0.22; p = 0.023) was found. Linear regression analyses were used to examine the associations of hepatic fat and dietary quality indicators as well as IR adjusted for potential confounders (sex, age and physical activity). The final models showed that HOMA-IR, GI, GL and TAC were able to explain between 22.4 and 22.8 % (p < 0.001) of the variability of liver fat content.DiscussionThe pathophysiology of NAFLD is thought to be associated with dietary determinants that contribute to metabolic dysregulation such as IR, ectopic liver fat deposition and hepatic damage. In accordance with other authors, we suggest that monitoring GI, GL and TAC may be useful approaches for the dietary treatment of NAFLD since they are related to hepatic fat. Additionally, it is important to highlight the essential role of IR in NAFLD as a key mediator in the development of NAFLD. Certainly, findings of the present study revealed a significant association of hepatic fat accumulation and IR.In summary, GI, GL and TAC are potential markers of diet quality, with an impact on susceptible population at hepatic risk.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Alessandro Mantovani ◽  
Graziana Petracca ◽  
Alessandro Csermely ◽  
Giorgia Beatrice ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Liver Fat ◽  
Controlled Trials ◽  
Liver Fat Content ◽  
Nonalcoholic Fatty Liver ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum liver enzyme levels and liver fat content on imaging techniques. Overall, we included a total of twelve RCTs testing the efficacy of dapagliflozin (n = six RCTs), empagliflozin (n = three RCTs), ipragliflozin (n = two RCTs) or canagliflozin (n = one RCT) to specifically treat NAFLD for a median period of 24 weeks with aggregate data on 850 middle-aged overweight or obese individuals with NAFLD (90% with type 2 diabetes). Compared to placebo/reference therapy, treatment with SGLT-2 inhibitors significantly decreased serum alanine aminotransferase (weighted mean differences (WMD): −10.0 IU/L, 95%CI −12.2 to −7.79 IU/L; I2 = 10.5%) and gamma-glutamyltransferase levels (WMD: −14.49 IU/L, 95%CI −19.35 to −9.63 IU/L, I2 = 38.7%), as well as the absolute percentage of liver fat content on magnetic resonance-based techniques (WMD: −2.05%, 95%CI −2.61 to −1.48%; I2 = 0%). In conclusion, SGLT-2 inhibitors seem to be a promising treatment option for NAFLD.

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