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.

Prevalence of non-alcoholic fatty liver disease in patients with chronic kidney disease: a case-control study

2021 ◽  
Author(s):  
Therese Adrian ◽  
Ida M H Sørensen ◽  
Filip K Knop ◽  
Susanne Bro ◽  
Ellen L F Ballegaard ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Liver Disease ◽  
Kidney Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

ABSTRACT Background Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis over non-alcoholic steatohepatitis with and without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far, there is scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate-to-severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD. Methods Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen Chronic Kidney Disease Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density <48 Hounsfield units was used as cut-off value for moderate-to-severe hepatic steatosis. Results The prevalence of moderate-to-severe hepatic steatosis was 7.9% and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled data set from both cohorts, adjusted odds ratios for moderate-to-severe hepatic steatosis among persons with diabetes, overweight and obesity amounted to 3.1 (95% confidence interval (CI) 1.6-5.9), 14.8 (95% CI 4.6-47.9) and 42.0 (95% CI 12.9-136.6), respectively. Conclusions In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate-to-severe hepatic steatosis as assessed by CT scan.

scholarly journals MON-597 Non-Alcoholic Fatty Liver Disease Determined by MRI and Its Association with Metabolic Variables in Non-Diabetic Subjects

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Debora Gonçalves Da Silva ◽  
Josue Da Silva Brito ◽  
Beatriz Francisco Barbosa Rodrigues ◽  
Daniele Martins Afonso ◽  
Angelica Amorim Amato
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Serum Levels ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Biochemical Variables ◽  
Metabolic Variables ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease determined by MRI and its association with metabolic variables in non-diabetic subjects Background: Non-alcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic steatosis (liver fat accumulation higher than 5% of liver weight) in the absence of other causes. Liver biopsy is recognized as a gold standard for diagnosis, but it is limited by the risks of serious complications. Besides that, the increasing prevalence of NASH led to improved imaging methods, such as Magnetic Resonance Imaging (MRI), that enable quantitative assessment of steatosis by quantifying the hepatic fat fraction (HFF), even with steatosis levels as low as 5.56%. Objective: The aim of this study was to evaluate the metabolic profile of patients without T2DM according to hepatic steatosis measured by MRI. Methods: This was cross-sectional study conducted in an Endocrinology Unity in Minas Gerais, Brazil. The study complied with the WMA Declaration of Helsinki and was approved by the Ethical Committee on Human Subject Research from the Faculty Patos de Minas. We recruited non-diabetic subjects aged above 20 years with hepatic steatosis detected by liver sonography. Exclusion criteria were alcohol consumption of more than 20 grams/day for female and 30 grams/day for male, ferritin serum levels above 1000 mg/dL, positive serology for hepatitis B or C and intake of medications known to produce hepatic steatosis. Included subjects underwent HFF quantification by MRI, and the degree of liver fatty infiltration was estimated by using chemical shift imaging. The following biochemical variables were assessed: fasting glucose and HbA1c, HOMA-IR, lipids, AST, ALT and GGT. Analysis: we grouped individuals according to the quartile of HFF and compared clinical and biochemical variables between the groups. Results: A total of 30 subjects (18 male and 12 females) were included. All subjects were overweight (10% overweight and 90% obese); 7 (23.3%) had 3 criteria and 16 (53.3%) had two criteria for MS. The only variable assessed herein that was different between males and females was HDL-c (40.5 vs 50.5 mg/dL, respectively, p=0.0255). ALT serum levels were significantly higher in subjects in the fourth quartile of HFF, when compared to those in the third quartile (76 vs 47 UI/L, respectively, p=0.037). The other clinical of biochemical variables assessed did not differ between the quartiles of HFF. Conclusion: our preliminary findings indicate that the biochemical variables related to metabolic homeostasis are poor predictors of the degree of liver fat in overweight non-diabetic subjects. Although screening for NAFLD is still a matter of debate, our results suggest that future discussions about this should take into account that excess body weight per se, independently from biochemical abnormalities, should be considered in the recommendations for screening non-diabetic subjects.

scholarly journals Newborn and childhood differential DNA methylation and liver fat in school-age children

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Madelon L. Geurtsen ◽  
Vincent W. V. Jaddoe ◽  
Lucas A. Salas ◽  
Susana Santos ◽  
Janine F. Felix
Keyword(s):  
Dna Methylation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
School Age Children ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Fat Fraction ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease is the most common chronic liver disease in children in western countries. Adverse early-life exposures are associated with higher liver fat percentages in children. Differential DNA methylation may underlie these associations. We aimed to identify differential DNA methylation in newborns and children associated with liver fat accumulation in childhood. We also examined whether DNA methylation at 22 cytosine-phosphate-guanine sites (CpGs) associated with adult non-alcoholic fatty liver disease is associated with liver fat in children. Within a population-based prospective cohort study, we analyzed epigenome-wide DNA methylation data of 785 newborns and 344 10-year-old children in relation to liver fat fraction at 10 years. DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Illumina). We measured liver fat fraction by Magnetic Resonance Imaging. Associations of single CpG DNA methylation at the two-time points with liver fat accumulation were analyzed using robust linear regression models. We also analyzed differentially methylation regions using the dmrff package. We looked-up associations of 22 known adult CpGs at both ages with liver fat at 10 years. Results The median liver fat fraction was 2.0% (95% range 1.3, 5.1). No single CpGs and no differentially methylated regions were associated with liver fat accumulation. None of the 22 known adult CpGs were associated with liver fat in children. Conclusions DNA methylation at birth and in childhood was not associated with liver fat accumulation in 10-year-old children in this study. This may be due to modest sample sizes or DNA methylation changes being a consequence rather than a determinant of liver fat.

scholarly journals The Impact of Macronutrient Intake on Non-alcoholic Fatty Liver Disease (NAFLD): Too Much Fat, Too Much Carbohydrate, or Just Too Many Calories?

2021 ◽  
Vol 8 ◽  
Author(s):  
Theresa Hydes ◽  
Uazman Alam ◽  
Daniel J. Cuthbertson
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lipid Storage ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic, in parallel with the obesity crisis, rapidly becoming one of the commonest causes of chronic liver disease worldwide. Diet and physical activity are important determinants of liver fat accumulation related to insulin resistance, dysfunctional adipose tissue, and secondary impaired lipid storage and/or increased lipolysis. While it is evident that a hypercaloric diet (an overconsumption of calories) promotes liver fat accumulation, it is also clear that the macronutrient composition can modulate this risk. A number of other baseline factors modify the overfeeding response, which may be genetic or environmental. Although it is difficult to disentangle the effects of excess calories vs. specifically the individual effects of excessive carbohydrates and/or fats, isocaloric, and hypercaloric dietary intervention studies have been implemented to provide insight into the effects of different macronutrients, sub-types and their relative balance, on the regulation of liver fat. What has emerged is that different types of fat and carbohydrates differentially influence liver fat accumulation, even when diets are isocaloric. Furthermore, distinct molecular and metabolic pathways mediate the effects of carbohydrates and fat intake on hepatic steatosis. Fat accumulation appears to act through impairments in lipid storage and/or increased lipolysis, whereas carbohydrate consumption has been shown to promote liver fat accumulation through de novo lipogenesis. Effects differ dependent upon carbohydrate and fat type. Saturated fat and fructose induce the greatest increase in intrahepatic triglycerides (IHTG), insulin resistance, and harmful ceramides compared with unsaturated fats, which have been found to be protective. Decreased intake of saturated fats and avoidance of added sugars are therefore the two most important dietary interventions that can lead to a reduction in IHTG and potentially the associated risk of developing type 2 diabetes. A healthy and balanced diet and regular physical activity must remain the cornerstones of effective lifestyle intervention to prevent the development and progression of NAFLD. Considering the sub-type of each macronutrient, in addition to the quantity, are critical determinants of liver health.

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