Efficacy of peroxisome proliferator-activated receptor agonists in diabetes and coronary artery disease

Abstract

The greatest clinical challenge in type 2 diabetes mellitus is the prevention of its long-term complications, many of which are of a cardiovascular nature. Despite the progress in cardiovascular risk management of diabetes patients using lipid-lowering and antihypertensive drugs, a substantial residual risk persists. Indeed, treated diabetes patients have a similar risk as untreated nondiabetic individuals. Although glycemic control through the use of antihyperglycemic agents improves microvascular complications, macrovascular disease risk is not reduced. These observations point to the need for additional therapeutic approaches in order to better control global cardiovascular risk. The peroxisome proliferator-activated receptor (PPAR) family members play major roles in the regulation of lipid and glucose metabolism and immune-inflammatory processes, making these transcription factors ideal targets for such therapeutic strategies. This review discusses our current knowledge of the effectiveness of PPAR-based therapeutics, focusing exclusively on cardiovascular disease in type 2 diabetes mellitus and the future prospects for novel generation of PPAR agonists.

Proteome Analysis Identified the PPARγ Ligand 15d-PGJ2 as a Novel Drug Inhibiting Melanoma Progression and Interfering with Tumor-Stroma Interaction

“…Shot gun analysis of 15d-PGJ2-treated A375 cells revealed 136 proteins which displayed increased peptide counts compared to the control (Table S2A, B). Amongst these we identified proteins involved in the lipid metabolism (protein count/peptide count = 7/7) such as thromboxane-A synthase, adipophilin, perilipin or apolipoprotein A-I (Table S2A, B) [22], [23]. Additionally, we detected the induction of HO-1 by 15d-PGJ2 (Table S2A, B) [24].…”

Tributyltin is a potent inhibitor of piscine peroxisome proliferator-activated receptor α and β

“…The role of PPARβ is less well understood, although various studies suggest that PPARβ has a role in global control of lipid homeostasis in mammals (Wagner and Wagner, 2010). Several synthetic PPAR agonists have been discovered and some are in use as drug treatments for dyslipidemia associated with coronary heart disease and diabetes (Fievet and Staels, 2009). …”

The effects of hydroalcoholic extract of spinach on prevention and treatment of some metabolic and histologic features in a rat model of nonalcoholic fatty liver disease

“…Prescription of spinach or thylakoid increased PPAR‐ γ gene expression in liver and adipose tissue in previous studies . Activation of PPAR‐ γ by increasing adiponectin circulating levels improved insulin resistance in peripheral tissues such as skeletal muscles and adipose tissue and reduced the transfer of fatty acids to the liver . Spinach is also a good source of lutein, quercetin, and other antioxidant compounds, which protect the liver against oxidative stress.…”