scholarly journals Advances in Unhealthy Nutrition and Circadian Dysregulation in Pathophysiology of NAFLD

2021 ◽  
Vol 2 ◽  
Author(s):  
Xin Guo ◽  
Juan Zheng ◽  
Shixiu Zhang ◽  
Xiaofan Jiang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Hepatic Steatosis ◽  
Nutrient Intake ◽  
Critical Factor ◽  
Therapeutic Strategies ◽  
Alcoholic Fatty Liver ◽  
Hepatic Glucose ◽  
Metabolic Conditions ◽  
Hepatic Fat ◽  
Alcoholic Fatty Liver Disease

Unhealthy diets and lifestyle result in various metabolic conditions including metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Much evidence indicates that disruption of circadian rhythms contributes to the development and progression of excessive hepatic fat deposition and inflammation, as well as liver fibrosis, a key characteristic of non-steatohepatitis (NASH) or the advanced form of NAFLD. In this review, we emphasize the importance of nutrition as a critical factor in the regulation of circadian clock in the liver. We also focus on the roles of the rhythms of nutrient intake and the composition of diets in the regulation of circadian clocks in the context of controlling hepatic glucose and fat metabolism. We then summarize the effects of unhealthy nutrition and circadian dysregulation on the development of hepatic steatosis and inflammation. A better understanding of how the interplay among nutrition, circadian rhythms, and dysregulated metabolism result in hepatic steatosis and inflammation can help develop improved preventive and/or therapeutic strategies for managing NAFLD.

scholarly journals Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3225
Author(s):  
Sanna Lensu ◽  
Raghunath Pariyani ◽  
Elina Mäkinen ◽  
Baoru Yang ◽  
Wisam Saleem ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Alcoholic Fatty Liver ◽  
Branched Chain Fatty Acids ◽  
Hepatic Fat ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
A Minor ◽  
Alcoholic Fatty Liver Disease

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

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 Prebiotic Xylo-oligosaccharides Targeting Faecalibacterium prausnitzii Prevent High Fat Diet-induced Hepatic Steatosis in Rats

2020 ◽  
Author(s):  
Sanna Lensu ◽  
Raghunath Pariyani ◽  
Elina Mäkinen ◽  
Baoru Yang ◽  
Wisam Saleem ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Beta Oxidation ◽  
Alcoholic Fatty Liver ◽  
Faecalibacterium Prausnitzii ◽  
Branched Chain Fatty Acids ◽  
Hepatic Fat ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
Alcoholic Fatty Liver Disease

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

scholarly journals Associations between Free Sugar and Sugary Beverage Intake in Early Childhood and Adult NAFLD in a Population-Based UK Cohort

Children ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 290
Author(s):  
Ahlia Sekkarie ◽  
Jean A. Welsh ◽  
Kate Northstone ◽  
Aryeh D. Stein ◽  
Usha Ramakrishnan ◽  
...  
Keyword(s):  
Total Energy ◽  
Hepatic Steatosis ◽  
Population Based ◽  
Free Sugar ◽  
Alcoholic Fatty Liver ◽  
Free Sugars ◽  
Logistic Regression Models ◽  
Sugar Intake ◽  
Sugary Beverages ◽  
Alcoholic Fatty Liver Disease

(1) Background: High sugar intake is prevalent among children and is associated with non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to determine if a high intake of free sugars and sugary beverages (SB) in childhood is associated with NAFLD in adulthood; (2) Methods: At 24 years, 3095 participants were assessed for severe hepatic steatosis (controlled attenuation parameter >280 dB/m) and had dietary data collected via a food frequency questionnaire at age three years. Multiple logistic regression models adjusted for total energy intake, potential confounders, and a mediator (offspring body mass index (BMI) at 24 years); (3) Results: Per quintile increase of free sugar intake association with severe hepatic steatosis at 24 years after adjusting for total energy was odds ratio (OR):1.07 (95% CL: 0.99–1.17). Comparing the lowest vs. the highest free sugar consumers, the association was OR:1.28 (95% CL: 0.88–1.85) and 1.14 (0.72, 1.82) after full adjustment. The OR for high SB consumption (>2/day) compared to <1/day was 1.23 (95% CL: 0.82–1.84) and OR: 0.98 (95% CL: 0.60–1.60) after full adjustment; (4) Conclusions: High free sugar and SB intake at three years were positively but weakly associated with severe hepatic steatosis at 24 years. These associations were completely attenuated after adjusting for confounders and 24-year BMI.

scholarly journals Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions

2021 ◽  
Vol 9 (5) ◽  
pp. 957
Author(s):  
Tomas Hrncir ◽  
Lucia Hrncirova ◽  
Miloslav Kverka ◽  
Robert Hromadka ◽  
Vladimira Machova ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Faecal Microbiota ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Immunological Mechanisms ◽  
Major Factors ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its worldwide prevalence is rapidly increasing and is currently estimated at 24%. NAFLD is highly associated with many features of the metabolic syndrome, including obesity, insulin resistance, hyperlipidaemia, and hypertension. The pathogenesis of NAFLD is complex and not fully understood, but there is increasing evidence that the gut microbiota is strongly implicated in the development of NAFLD. In this review, we discuss the major factors that induce dysbiosis of the gut microbiota and disrupt intestinal permeability, as well as possible mechanisms leading to the development of NAFLD. We also discuss the most consistent NAFLD-associated gut microbiota signatures and immunological mechanisms involved in maintaining the gut barrier and liver tolerance to gut-derived factors. Gut-derived factors, including microbial, dietary, and host-derived factors involved in NAFLD pathogenesis, are discussed in detail. Finally, we review currently available diagnostic and prognostic methods, summarise latest knowledge on promising microbiota-based biomarkers, and discuss therapeutic strategies to manipulate the microbiota, including faecal microbiota transplantation, probiotics and prebiotics, deletions of individual strains with bacteriophages, and blocking the production of harmful metabolites.

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