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 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 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 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 RIPK3 acts as a lipid metabolism regulator contributing to inflammation and carcinogenesis in non-alcoholic fatty liver disease

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321767
Author(s):  
Marta B Afonso ◽  
Pedro M Rodrigues ◽  
Miguel Mateus-Pinheiro ◽  
André L Simão ◽  
Maria M Gaspar ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Body Weight Gain ◽  
Control Diet ◽  
Peroxisome Proliferator ◽  
Functional Link ◽  
Alcoholic Fatty Liver ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

ObjectiveReceptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD.DesignRIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or Ripk3-deficient (Ripk3−/−) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks.ResultsRIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly, Ripk3 deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were reduced in Ripk3−/− mice. Furthermore, Ripk3 deficiency hampered tumourigenesis. Intriguingly, Ripk3−/− mice displayed increased body weight gain, while lipidomics showed that deletion of Ripk3 shifted hepatic lipid profiles. Peroxisome proliferator-activated receptor γ (PPARγ) was increased in Ripk3−/− mice and negatively correlated with hepatic RIPK3 in patients with NAFLD. Mechanistic studies established a functional link between RIPK3 and PPARγ in controlling fat deposition and fibrosis.ConclusionHepatic RIPK3 correlates with NAFLD severity in humans and mice, playing a key role in managing liver metabolism, damage, inflammation, fibrosis and carcinogenesis. Targeting RIPK3 and its intricate signalling arises as a novel promising approach to treat NASH and arrest disease progression.

scholarly journals Hepatic lipid saturation indices and insulin resistance in non‐alcoholic fatty liver disease (NAFLD)

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Jacob M Haus ◽  
Thomas PJ Solomon ◽  
Lan Lu ◽  
Arthur J McCullough ◽  
Chris A Flask ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Saturation Indices ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Alcoholic Fatty Liver Disease
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