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Role of selective peroxisome proliferator‐activated receptor modulators in managing cardiometabolic disease: tale of a roller‐coaster

Sahebkar, A.; Watts, G. F.

Diabetes, obesity & metabolism. Volume 16:Issue 9 (2014, September); pp 780-792 -- [John Wiley & Sons Ltd]

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  • Title:
    Role of selective peroxisome proliferator‐activated receptor modulators in managing cardiometabolic disease: tale of a roller‐coaster
  • Author: Sahebkar, A.;
    Watts, G. F.
  • Found In: Diabetes, obesity & metabolism. Volume 16:Issue 9 (2014, September); pp 780-792
  • Journal Title: Diabetes, obesity & metabolism
  • Subjects: Clinical pharmacology--Periodicals; Diabetes--Periodicals; Metabolism--Disorders--Periodicals; Obesity--Periodicals; Dewey: 616.462
  • Rights: legaldeposit
  • Publication Details: [John Wiley & Sons Ltd]
  • Abstract: Abstract

    Atherogenic dyslipidaemia is a hypertriglyceridaemic phenotype, associated with increased plasma concentrations of small, dense low‐density lipoprotein (sdLDL) particles, triglyceride‐rich lipoproteins (TRLs) and non‐high‐density lipoprotein cholesterol (non‐HDL‐C), and low HDL particles. Atherogenic dyslipidaemia commonly accompanies several metabolic disorders including type 2 diabetes, metabolic syndrome, non‐alcoholic fatty liver disease (NAFLD) and obesity, and increases the risk of cardiovascular disease (CVD). Statins significantly lower plasma LDL‐cholesterol and CVD risk, but their efficacy in correcting hypertriglyceridaemia is limited. Untreated hypertriglyceridaemia may partly account for residual risk of CVD in patients on statin treatment. Activators of peroxisome proliferator‐activated receptor (PPAR) α are more effective in correcting TRL and HDL metabolism than statins. A dual PPARα/δ agonist (GFT‐505) may have additional benefits on hepatic insulin sensitivity, steatosis and fibrosis. Selective PPAR modulators (SPPARMs) have the potential of increasing therapeutic specificity, while reducing unwanted off‐target effects. This review provides a summary of findings from randomized controlled trials of the efficacy of fenofibrate (as the most widely used PPARα agonist) and novel selective PPARα (ABT‐335 and k‐877), PPARα/δ (GFT‐505), PPARδ (MBX‐8025 and GW501516) and PPARγ (INT131) agonists in the treatment of atherogenic dyslipidaemia and NAFLD.


  • Identifier: ETOClsidyv8b32e46a; System Number: LDEAvdc_100024897517.0x000001; Journal ISSN: 1462-8902; 10.1111/dom.12277
  • Publication Date: 2014
  • Physical Description: Electronic
  • Shelfmark(s): ELD Digital store

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