The central role of fat and effect of peroxisome proliferator-activated receptor-gamma on progression of insulin resistance and cardiovascular disease.
ABSTRACT Recent evidence suggests that progression of insulin resistance parallels progression of atherosclerosis. Fat plays an integral role in the development of type 2 diabetes and vascular injury. The balance of adipose-derived substances, including free fatty acids, tumor necrosis factor-alpha, leptin, adiponectin, and plasminogen activator inhibitor-1, determine both insulin action and the state of vascular inflammation. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands promote the balance of these substances to enhance insulin-mediated glucose uptake and decrease inflammation. PPAR-gamma ligands reverse the major defect of the insulin resistance syndrome and have important effects that inhibit atherosclerosis, improve endothelial cell function, and attenuate inflammation. Although more research is needed, data suggest that PPAR-gamma ligands may prevent the progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis.
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ABSTRACT: Rosiglitazone is PPARγ synthetic activator from the group of thiazolidinediones often used in the treatment of chronic diseases such as type 2 diabetes and other forms of insulin resistance. The present in vitro study assessed the direct effects of rosiglitazone at 25 and 50 μM doses on PPARγ expression, steroid secretion (progesterone - P4, androstenedione - A4, testosterone - T, and estradiol - E2) and protein expression of PPARγ, 3βHSD, CYP17, 17βHSD, CYP19 by porcine ovarian follicles from prepubertal and cycling animals. We analyzed also steroid enzymatic activity by conversion of P5 to P4, P4 to A4 and A4 to T. Our results indicated that rosiglitazone increased significantly PPARγ expression, P4 secretion, 3βHSD activity and protein expression. Rosiglitazone decreased A4 and T secretion by reducing the expression and activity of CYP17 and 17βHSD and did not change E2 secretion and CYP19. Similarly results was observed both in prepubertal and cycling pigs. Our results indicate that these direct effects of rosiglitazone on ovarian steroidogenesis provide a framework for testing several potential new mechanisms of PPAR-γ actions on porcine ovarian function.Theriogenology 07/2014; 82(1). DOI:10.1016/j.theriogenology.2014.02.016 · 1.85 Impact Factor
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ABSTRACT: Diseases of the central nervous system present a challenge for the development of new therapeutic agents. Nuclear receptors are ligand-activated transcription factors that have proven to be valuable targets for development of new drugs owing to their ability to directly regulate gene expression. The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), has been investigated for its action in ameliorating the development and progression of a number of CNS diseases. PPARgamma agonists exhibit potent anti-inflammatory effects and appear to have direct neuroprotective actions. PPARgamma agonists have been shown to be efficacious in animal models of Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis. The availability of FDA-approved agonists of this receptor will facilitate the rapid translation of these findings into clinical trials for a number of CNS diseases.Neurochemistry International 08/2006; 49(2):136-44. DOI:10.1016/j.neuint.2006.03.020 · 2.65 Impact Factor
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ABSTRACT: The aim of this article is to review the lessons on the relationship between GH and the principal metabolic cardiovascular risk factors that we learned from studies of GH deficiency (GHD) in the adult. The lesson that "organic" GHD has taught us is that primary impairment in the GH/IGF-I axis may lead to a high-risk cardiovascular profile that is partially reversible during GH replacement. Waiting for the definitive demonstration that GH substitution may reduce cardiovascular mortality in these patients, we find that data so far reported are encouraging and indicate in the beneficial cardiovascular effects of GH one of the major factors supporting this type of treatment in hypopituitary GHD adults. Moreover, enough evidence from GHD studies has been produced to suggest a physiological role for the GH/IGF-I axis in the control and regulation of several metabolic cardiovascular risk factors.Journal of Clinical Endocrinology & Metabolism 04/2005; 90(3):1864-70. DOI:10.1210/jc.2004-0545 · 6.31 Impact Factor