scholarly journals Interactions between Host PPARs and Gut Microbiota in Health and Disease

2019 ◽  
Vol 20 (2) ◽  
pp. 387 ◽  
Author(s):  
Arif Hasan ◽  
Asadur Rahman ◽  
Hiroyuki Kobori
Keyword(s):  
Gut Microbiota ◽  
Gastrointestinal Disorders ◽  
Peroxisome Proliferator ◽  
Human Gastrointestinal Tract ◽  
Alcoholic Fatty Liver ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Peroxisome Proliferator Activated Receptors ◽  
Visceral Adipose ◽  
Alcoholic Fatty Liver Disease

The human gastrointestinal tract is inhabited by many types of microbiota, including bacteria, viruses, and fungi. Dysregulations of their microenvironment are associated with various health problems, not only limited to gastrointestinal disorders, such as inflammatory bowel disease, but to impacts beyond the intestine. For example, intestinal microbiota can affect the liver in non-alcoholic fatty liver disease, visceral adipose tissue during adipogenesis, and the heart in atherosclerosis. The factors contributing to these pathogeneses involve the gut microbiota and the effector organs of the host, and everything in between. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) are pivotal for the modulation of many of the pathogeneses mentioned above. It is, therefore, conceivable that, in the process of host-microbiota interactions, PPARs play important roles. In this review, we focus on the interactions between host PPARs in different organs and gut microbiota and their impacts on maintaining health and various diseases.

scholarly journals Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk

2020 ◽  
Vol 21 (7) ◽  
pp. 2391 ◽  
Author(s):  
Rohit A. Sinha ◽  
Sangam Rajak ◽  
Brijesh K. Singh ◽  
Paul M. Yen
Keyword(s):  
Energy Metabolism ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Reciprocal Regulation ◽  
Alcoholic Fatty Liver ◽  
Lysosomal Activity ◽  
Hepatic Lipid ◽  
Peroxisome Proliferator Activated Receptors ◽  
Key Aspects ◽  
Alcoholic Fatty Liver Disease

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).

scholarly journals The gut microbial metabolome: modulation of cancer risk in obese individuals

2012 ◽  
Vol 72 (1) ◽  
pp. 178-188 ◽  
Author(s):  
Wendy R. Russell ◽  
Sylvia H. Duncan ◽  
Harry J. Flint
Keyword(s):  
Gut Microbiota ◽  
Genetic Factors ◽  
Microbial Metabolism ◽  
Health Concern ◽  
Human Gut ◽  
Alcoholic Fatty Liver ◽  
Health And Disease ◽  
Diet And Lifestyle ◽  
Alcoholic Fatty Liver Disease

Obesity is a critical health concern and although genetic factors may predispose an individual to become obese, changes in diet and lifestyle over the last few decades are likely to be significant contributors. Even so, it has been suggested that the causes of the current obesity crisis are not simply explained by changes in eating and exercise habits. Evidence suggests that the gut microbiota may play an important role in obesity and may be a factor in the development of associated disease including diabetes, CVD, non-alcoholic fatty liver disease and cancer. There have been tremendous advances in knowledge regarding the composition of human gut microbiota, but less is known about their function and role within the human host. It is becoming widely accepted that the products of microbial metabolism influence human health and disease, particularly with respect to immune response and inflammation. However, in most cases, the products of microbial metabolism are uncharacterised and their mechanism of action remains unknown. This review addresses the role of the metabolites produced by gut microbiota in cancer and obesity. It is clear that only if the link between microbial diversity and metabolic functionality is firmly established, will the mechanism by which gut microbiota maintains health or contributes to disease development be elucidated.

scholarly journals The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease

2017 ◽  
Vol 67 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Xin Sun ◽  
Yan Zhang ◽  
Meilin Xie
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Peroxisome Proliferator Activated Receptors ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.

scholarly journals Microbial Population Changes and Their Relationship with Human Health and Disease

2019 ◽  
Vol 7 (3) ◽  
pp. 68 ◽  
Author(s):  
Ana Álvarez-Mercado ◽  
Miguel Navarro-Oliveros ◽  
Cándido Robles-Sánchez ◽  
Julio Plaza-Díaz ◽  
María Sáez-Lara ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Future Directions ◽  
Alcoholic Fatty Liver ◽  
Targeted Interventions ◽  
Number Of Factors ◽  
Health And Disease ◽  
Inflammatory Bowel

Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.

scholarly journals Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1638 ◽  
Author(s):  
Anne Fougerat ◽  
Alexandra Montagner ◽  
Nicolas Loiseau ◽  
Hervé Guillou ◽  
Walter Wahli
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.

scholarly journals A214 BARIATRIC SURGERY PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE HAVE DIFFERENT VISCERAL ADIPOSE TISSUE GENE EXPRESSION COMPARED TO THOSE WITH NORMAL LIVER

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 245-247
Author(s):  
S Keshavjee ◽  
J Yadav ◽  
K Schwenger ◽  
S Fischer ◽  
T D Jackson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bariatric Surgery ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Inflammatory Markers ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Visceral Adipose ◽  
Healthy Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation. Aims This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX. Methods Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05. Results We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL. Conclusions Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity. Funding Agencies CIHRCanadian Liver foundation

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