scholarly journals PncA from bacteria improves diet-induced NAFLD by enabling the transition from NAM to NA in mice

2021 ◽  
Author(s):  
Shengyu Feng ◽  
Liuling Guo ◽  
Hailiang Liu
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Cultured Cells ◽  
List Type ◽  
Host Liver ◽  
First Line ◽  
Synthesis Inhibitor ◽  
Alcoholic Fatty Liver ◽  
Nad Metabolism ◽  
Damage Repair ◽  
Alcoholic Fatty Liver Disease

AbstractNicotinamide adenine dinucleotide (NAD+) is crucial for energy metabolism, oxidative stress, DNA damage repair, longevity regulation, and several signaling processes. To date, three NAD+ synthesis pathways have been found in microbiota and hosts, but the potential relationship between gut microbiota and their hosts in regulating NAD+ homeostasis remains unknown. Here, we show that an analog of the first-line tuberculosis drug pyrazinamide (a bacterial NAD+ synthesis inhibitor) affected NAD+ levels in the intestines and liver of mice and disrupted the intestinal microecological balance. Furthermore, using microbiota expressing the pyrazinamidase/nicotinamidase (PncA) gene, which is a target of pyrazinamide, hepatic NAD+ levels were greatly increased and significantly increased compared with other NAD+ precursors, and diet-induced non-alcoholic fatty liver disease (NAFLD) in mice was improved. Overall, the PncA gene in microbiota plays an important role in regulating NAD+ synthesis in the host, thereby providing a potential target for modulating the host’s NAD+ level.HighlightsPncA inhibitors disrupt gut microbiome homeostasis and reduce host NAD+ levels but do not affect NAD+ levels in cultured cellsPncA gene in microbiota affects host liver NAD metabolismPncA affects lipid metabolism-related genes and metabolites in mice with NAFLDDiet-induced NAFLD is improved by PncA overexpression in the liver of miceGraphical abstract

scholarly journals Diet and Non-Alcoholic Fatty Liver Disease: The Mediterranean Way

2019 ◽  
Vol 16 (17) ◽  
pp. 3011 ◽  
Author(s):  
Ludovico Abenavoli ◽  
Luigi Boccuto ◽  
Alessandro Federico ◽  
Marcello Dallio ◽  
Carmelina Loguercio ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Dairy Products ◽  
Fatty Liver Disease ◽  
Inverse Association ◽  
First Line ◽  
Alcoholic Fatty Liver ◽  
Risk Of Mortality ◽  
Alcoholic Fatty Liver Disease

Lifestyle interventions remain the first-line treatment for non-alcoholic fatty liver disease (NAFLD), even if the optimal alimentary regimen is still controversial. The interest in antioxidants has increased over time, and literature reports an inverse association between nutrients rich in antioxidants and the risk of mortality due to non-communicable diseases, including NAFLD. Mediterranean diet (MD) is a model characterized by main consumption of plant-based foods and fish and reduced consumption of meat and dairy products. MD represents the gold standard in preventive medicine, probably due to the harmonic combination of many foods with antioxidant and anti-inflammatory properties. This regimen contributes substantially to the reduction of the onset of many chronic diseases as cardiovascular diseases, hypertension, type 2 diabetes mellitus, obesity, cancer, and NAFLD. The present review aims to clarify the intake of antioxidants typical of the MD and evaluate their effect on NAFLD.

scholarly journals Impaired base excision repair is related to the pathogenesis of non-alcoholic fatty liver disease

2020 ◽  
Vol 16 ◽  
pp. 5-11
Author(s):  
Sylwia Ziółkowska ◽  
Piotr Czarny ◽  
Janusz Szemraj
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Liver Disorder ◽  
Alcoholic Fatty Liver ◽  
Aggressive Form ◽  
Damage Repair ◽  
Underlying Basis ◽  
Base Excision ◽  
Specific Symptoms ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty disease (NAFLD) is a liver disorder that affects up to 30% of the population, mainly in Western countries. It is estimated that up to 75% of NAFLD patients will develop a more aggressive form of the disease, non-alcoholic steatohepatitis (NASH). NAFLD can lead to fibrosis and liver failure; however, it is difficult to diagnose NAFLD due to its non-specific symptoms. Unfortunately, there is no treatment available for this disease. The risk factors of NAFLD are obesity and insulin resistance (IR). The molecular factors that seem to play an important role in the pathogenesis of NAFLD are oxidative stress as well as impaired DNA damage repair processes; a great body of evidence confirms an association with the base excision repair (BER) pathway. The activity of BER is decreased in patients with NAFLD and in animal models of this disease. In order to better understand the underlying basis of the disease, knowledge should be broadened in the area of DNA repair in NAFLD.

scholarly journals INTESTINAL GLUCONEOGENESIS IS DOWNREGULATED IN PAEDIATRIC PATIENTS WITH COELIAC DISEASE

2021 ◽  
Author(s):  
Olof Karlson ◽  
Henrik Arnell ◽  
Audur H. Gudjonsdottir ◽  
Daniel Agardh ◽  
Åsa Torinsson Naluai
Keyword(s):  
Coeliac Disease ◽  
Fatty Liver Disease ◽  
Target Genes ◽  
List Type ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Intestinal Gluconeogenesis ◽  
Alcoholic Fatty Liver Disease ◽  
Duodenal Biopsies ◽  
Lower Expression

ABSTRACTObjectiveUntreated coeliac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated coeliac disease.DesignQuantitative polymerase chain reaction (qPCR) was used to quantify expression of 11 target genes related to IGN using the delta-delta Ct method with three reference genes (GUSB, IPO8 and YWHAZ) in duodenal biopsies collected from 84 children with untreated coeliac disease and 58 disease controls.ResultsSignificantly lower expression of nine target genes involved in IGN was seen in duodenal biopsies from CD patients compared with controls: FBP1, G6PC, GLS, GPT1, PCK1, PPARGC1A, SLC2A2, SLC5A1, and SLC6A19. No significant differences in expression were seen for G6PC3 and GOT1.ConclusionChildren with untreated coeliac disease have lower expression of genes important for IGN. Further studies are warranted to disentangle whether this is a consequence of intestinal inflammation or due to an impaired metabolic pathway shared with other chronic metabolic diseases. Impaired IGN could be a mechanism behind the increased risk of NAFLD seen in CD patients.SIGNIFICANCE OF THIS STUDYWhat is already known about this subject?Genome-wide association studies have shown an association between coeliac disease (CD) and glutaminase (GLS).Intestinal gluconeogenesis (IGN) is a process with a recently described important function in energy homeostasis and metabolic disease. GLS is critical for IGN by enabling it to use glutamine, its main substrate.CD patients are at an increased risk of non-alcoholic fatty liver disease (NAFLD) as adults.What are the new findings?Nine genes involved in IGN are downregulated at the gene expression level in the small intestine of children with untreated CD, suggesting impairment of IGN.How might it impact on clinical practice in the foreseeable future?Impaired IGN might be a mechanism behind the increased risk of NAFLD seen in CD patients as adults.Early diagnosis and treatment of CD may restore IGN and prevent CD patients from NAFLD later in adulthood.

scholarly journals LIFESTYLE CHANGES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW PROTOCOL

2020 ◽  
Author(s):  
Tiziana Fernández-Mincone ◽  
Macarena Viñuela Morales ◽  
Marco Arrese Jiménez ◽  
Juan Pablo Arab Verdugo ◽  
Daniel Cabrera ◽  
...  
Keyword(s):  
Weight Loss ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Changes ◽  
Pharmacological Treatments ◽  
First Line ◽  
Alcoholic Fatty Liver ◽  
Review Protocol ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is a worldwide raising liver condition and it is expected to become the first cause of progression to cirrhosis and hepatocellular carcinoma in the next 5 years (Araújo 2018). At present, there are no pharmacological treatments approved. Weight loss is the first-line treatment (European Association for the Study of the Liver 2016) (Chalasani 2012) showing that 7 to 10% weight loss improves steatosis, inflammation, hepatocyte ballooning and, in NASH patients, has an impact in fibrosis too (Romero-Gómez 2017). However, the reduction and maintenance of weight loss is often complex. To achieve this goal, it is recommended doing lifestyle changes including exercise and diet on daily living (Hannah 2016). However, it has been difficult to establish any conclusions regarding the best type of diet or exercise protocol to maximize improvements and to maintain its effects through time. Because of this, the objective of this review is assessing the efficacy and safety of diet, exercise, or a combination of these in patients with NAFLD.

scholarly journals Identification of the keystone species in non-alcoholic fatty liver disease by causal inference and dynamic intervention modeling

2020 ◽  
Author(s):  
Dingfeng Wu ◽  
Na Jiao ◽  
Ruixin Zhu ◽  
Yida Zhang ◽  
Wenxing Gao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Causal Inference ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Keystone Species ◽  
List Type ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

ABSTRACTObjectiveKeystone species are required for the integrity and stability of an ecological community, and therefore, are potential intervention targets for microbiome related diseases.DesignHere we describe an algorithm for the identification of keystone species from cross-sectional microbiome data of non-alcoholic fatty liver disease (NAFLD) based on causal inference theories and dynamic intervention modeling (DIM).ResultsEight keystone species in the gut of NAFLD, represented by P. loveana, A. indistinctus and D. pneumosintes, were identified by our algorithm, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome with 92.3% recovery. These keystone species regulate intestinal amino acids metabolism and acid-base environment to promote the growth of the butyrate-producing Lachnospiraceae and Ruminococcaceae species.ConclusionOur method may benefit microbiome studies in the broad fields of medicine, environmental science and microbiology.SUMMARYWhat is already known about this subject?Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disease whose pathogenesis remains unclear.Dysbiosis in the gut microbiota affects the initiation and development of NAFLD, but the mechanisms is yet to be established.Keystone species represent excellent candidate targets for gut microbiome-based interventions, as they are defined as the species required for the integrity and stability of the ecological system.What are the new findings?NAFLD showed significant dysbiosis in butyrate-producing Lachnospiraceae and Ruminococcaceae species.Microbial interaction networks were constructed by the novel algorithm with causal inference.Keystone species were identified form microbial interaction networks through dynamic intervention modeling based on generalized Lotka-Volterra model.Eight keystone species of NAFLD with the highest potential for restoring the microbial composition were identified.How might it impact on clinical practice in the foreseeable future?An algorithm for the identification of keystone species from cross-sectional microbiome data based on causal inference theories and dynamic intervention modeling.Eight keystone species in the gut of NAFLD, represented by P. loveana, A. indistinctus and D. pneumosintes, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome.Our method may benefit microbiome studies in the broad fields of medicine, environmental science and microbiology.

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.

Sign in / Sign up

Export Citation Format

Share Document