Premium
Role of selective peroxisome proliferator‐activated receptor modulators in managing cardiometabolic disease: tale of a roller‐coaster
Author(s) -
Sahebkar A.,
Watts G. F.
Publication year - 2014
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12277
Subject(s) - fenofibrate , medicine , endocrinology , peroxisome proliferator activated receptor , ppar agonist , type 2 diabetes , hypertriglyceridemia , fatty liver , rosiglitazone , steatosis , metabolic syndrome , nonalcoholic fatty liver disease , diabetes mellitus , triglyceride , cholesterol , receptor , disease
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 .