Thiazolidinediones

Publication Title: 
Planta Medica

Medicinal plants are a rich source of ligands for nuclear receptors. The present study was aimed to screen a collection of plant extracts for PPAR?/?-activating properties and identify the active extract that can stimulate cellular glucose uptake without enhancing the adipogenesis. A reporter gene assay was performed to screen ethanolic extracts of 263 plant species, belonging to 94 families, for activation of PPAR? and PPAR?. Eight extracts showed activation of PPAR?, while 22 extracts showed activation of PPAR?.

Author(s): 
Yang, Min Hye
Avula, Bharathi
Smillie, Troy
Khan, Ikhlas A.
Khan, Shabana I.
Publication Title: 
PloS One

Nutrient-deprivation autophagy factor-1 (NAF-1) (synonyms: Cisd2, Eris, Miner1, and Noxp70) is a [2Fe-2S] cluster protein immune-detected both in endoplasmic reticulum (ER) and mitochondrial outer membrane. It was implicated in human pathology (Wolfram Syndrome 2) and in BCL-2 mediated antagonization of Beclin 1-dependent autophagy and depression of ER calcium stores. To gain insights about NAF-1 functions, we investigated the biochemical properties of its 2Fe-2S cluster and sensitivity of those properties to small molecules.

Author(s): 
Tamir, Sagi
Zuris, John A.
Agranat, Lily
Lipper, Colin H.
Conlan, Andrea R.
Michaeli, Dorit
Harir, Yael
Paddock, Mark L.
Mittler, Ron
Cabantchik, Zvi Ioav
Jennings, Patricia A.
Nechushtai, Rachel
Publication Title: 
Arteriosclerosis, Thrombosis, and Vascular Biology

OBJECTIVE: The purpose of this research was to evaluate the short-term effects of pioglitazone (PIO) on high-density lipoprotein cholesterol (HDL-C) and other metabolic parameters in nondiabetic patients with metabolic syndrome (MetSyn). METHODS AND RESULTS: Sixty nondiabetic adults with low HDL-C and MetSyn were randomized to PIO or matching placebo for 12 weeks. PIO increased HDL-C by 15% and 14% at 6 and 12 weeks, respectively, compared with placebo (P<0.001). Changes in HDL-C were correlated to changes in adiponectin (r=0.34; P=0.01) but not to changes in insulin resistance.

Author(s): 
Szapary, Philippe O.
Bloedon, Leanne T.
Samaha, Frederick F.
Duffy, Danielle
Wolfe, Megan L.
Soffer, Daniel
Reilly, Muredach P.
Chittams, Jesse
Rader, Daniel J.
Publication Title: 
Journal of Molecular Endocrinology

The zebrafish model system is one of the most widely used animal models for developmental research and it is now becoming an attractive model for drug discovery and toxicological screening. The completion of sequencing the zebrafish genome and the availability of full-length cDNAs and DNA microarrays for expression analysis, in addition to techniques for generating transgenic lines and targeted mutations, have made the zebrafish model even more attractive to researchers.

Author(s): 
Elo, B.
Villano, C. M.
Govorko, D.
White, L. A.
Publication Title: 
Diabetes, Obesity & Metabolism

AIM: To elucidate the mechanism by which rosiglitazone regulates adipose triglyceride lipase (ATGL). METHODS: Male C57Bl/6 mice were treated with rosiglitazone daily (10 mg/kg body weight), and adipose tissues were weighed and preserved for mRNA and protein analysis of ATGL. In parallel, preadipocyte (3T3-L1) cells were differentiated with insulin/dexamethasone/3-isobutyl-1-methlxanthine cocktail or rosiglitazone, and ATGL levels were measured with real-time PCR, western blotting and immunohistochemistry.

Author(s): 
Liu, L.-F.
Purushotham, A.
Wendel, A. A.
Koba, K.
DeIuliis, J.
Lee, K.
Belury, M. A.
Publication Title: 
Endocrinology

Toll-like receptors (TLRs) are key innate immune sensors of endogenous damage signals and play an important role in inflammatory diseases like diabetes and atherosclerosis. Pioglitazone (PIO), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, has been reported to be an antiinflammatory agent. Thus, in the present study, we examined the antiinflammatory effects of PIO on TLR2 and TLR4 expression in human monocytes exposed to Pam3CSK4 (Pam; TLR2 ligand) and purified lipopolysaccharide (LPS; TLR4 ligand) using flow cytometry and real-time RT-PCR.

Author(s): 
Dasu, Mohan R.
Park, Samuel
Devaraj, Sridevi
Jialal, Ishwarlal
Publication Title: 
Clinical Nutrition (Edinburgh, Scotland)

BACKGROUND & AIMS: Abscisic acid (ABA) is effective in preventing insulin resistance and obesity-related inflammation through a PPAR γ-dependent mechanism. The objective of this study was to assess the efficacy ABA in improving glucose homeostasis and suppress inflammation when administered in combination with rosiglitazone (Ros) and to determine whether PPAR γ activation by ABA is initiated via cAMP/protein kinase A (PKA) signaling. METHODS: Obese db/db mice were fed high-fat diets containing 0, 10, or 70 mg/kg Ros with and without racemic ABA (100 mg/kg) for 60 days.

Author(s): 
Guri, Amir J.
Hontecillas, Raquel
Bassaganya-Riera, Josep
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity.

Author(s): 
Yarasheski, Kevin E.
Cade, W. Todd
Overton, E. Turner
Mondy, Kristin E.
Hubert, Sara
Laciny, Erin
Bopp, Coco
Lassa-Claxton, Sherry
Reeds, Dominic N.
Publication Title: 
Mucosal Immunology

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IBD. This study aimed to characterize the mechanisms underlying the beneficial effects of macrophage PPAR-γ in IBD.

Author(s): 
Hontecillas, R.
Horne, W. T.
Climent, M.
Guri, A. J.
Evans, C.
Zhang, Y.
Sobral, B. W.
Bassaganya-Riera, J.
Publication Title: 
Pharmacological Research: The Official Journal of the Italian Pharmacological Society

Clinical studies suggest that rosiglitazone (RSG) treatment may increase the incidence of heart failure in diabetic patients. In this study, we examined whether a high corn oil diet with RSG treatment in insulin resistant aging mice exerted metabolic and pro-inflammatory effects that stimulate cardiac dysfunction. We also evaluated whether fish oil attenuated these effects. Female C57BL/6J mice (13 months old) were divided into 5 groups: (1) lean control (LC), (2) corn oil, (3) fish oil, (4) corn oil+RSG and (5) fish oil+RSG.

Author(s): 
Halade, Ganesh V.
Williams, Paul J.
Lindsey, Merry L.
Fernandes, Gabriel

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