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A role of peroxisome proliferator-activated receptor ? in non-alcoholic fatty liver disease.

ABSTRACT: Non-alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options. Thiazolidinediones target the nuclear receptor peroxisome proliferator-activated receptor ? (PPAR?) and have been investigated in several clinical trials for their potential in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). PPAR? has specialized roles in distinct tissues and cell types, and although the primary function of PPAR? is in adipose tissue, where the highest expression levels are observed, hepatic expression levels of PPAR? are significantly increased in patients with NAFLD. Thus, NAFLD patients receiving treatment with PPAR? agonists might have a liver response apart from the one in adipose tissue. Owing to the different roles of PPAR?, new treatment strategies include development of compounds harnessing the beneficial effects of PPAR? while restricting PPAR? unwanted effects such as adipogenesis resulting in weight gain. Furthermore, dual or pan agonists targeting two or more of the PPARs have shown promising results in pre-clinical research and some are currently proceeding to clinical trials. This MiniReview explores adipose- and liver-specific actions of PPAR?, and how this knowledge may contribute in the search for new treatment modalities in NAFLD/NASH.

SUBMITTER: Skat-Rordam J

PROVIDER: S-EPMC6850367 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A role of peroxisome proliferator-activated receptor γ in non-alcoholic fatty liver disease.

Skat-Rørdam Josephine J Højland Ipsen David D Lykkesfeldt Jens J Tveden-Nyborg Pernille P

Basic & clinical pharmacology & toxicology 20190122 5

Non-alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options. Thiazolidinediones target the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and have been investigated in several clinical trials for their potential in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). PPARγ has specialized roles in distinct tissues and cell types, and although the primary fun ...[more]

PMID: 30561132

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Project description:BackgroundSaroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India.MethodsIn this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study.ResultsIn 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies.ConclusionSaroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

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A role of peroxisome proliferator-activated receptor ? in non-alcoholic fatty liver disease.

Publications

A role of peroxisome proliferator-activated receptor γ in non-alcoholic fatty liver disease.

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