ABSTRACT PPARδ belongs to the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors. Upon activation by an agonist, PPARδ controls a variety of physiological processes via regulation of its target genes. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a cyclopentenone prostaglandin that features an electrophilic, α,β-unsaturated ketone (an enone) in the cyclopentenone ring. Many of 15d-PGJ2’s biological effects resultRead More
GPR40 partial agonist MK-2305 lower fasting glucose in the Goto Kakizaki rat via suppression of endogenous glucose production
ABSTRACT GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partialRead More
Triazolone Compounds and Uses Thereof Application 20160194292
ABSTRACT The invention disclosed herein is directed to compounds of Formula (1a) and (1b) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocyticδ leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (1a) orRead More
Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists
ABSTRACT Diabetes mellitus is a chronic metabolic disorder that affects more than 180 million people worldwide. Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors that have been targeted by the thiazolidinedione (TZD) class of compounds for the management of type II diabetes. PPARγ is known to regulate adipogenesis and glucose metabolism. AnotherRead More
Systems toxicology identifies mechanistic impacts of 2-amino-4,6-dinitrotoluene (2A-DNT) exposure in Northern Bobwhite
ABSTRACT Background: A systems toxicology investigation comparing and integrating transcriptomic and proteomic results was conducted to develop holistic effects characterizations for the wildlife bird model, Northern bobwhite (Colinus virginianus) dosed with the explosives degradation product 2-amino-4,6-dinitrotoluene (2A-DNT). A subchronic 60d toxicology bioassay was leveraged where both sexes were dosed via daily gavage with 0, 3, 14, or 30 mg/kg-dRead More
Keratinocyte differentiation and upregulation of ceramide synthesis induced by an oat lipid extract via the activation of PPAR pathways
ABSTRACT Activation of peroxisome proliferator-activated receptors (PPARs) has been shown to have an important role in skin barrier function by regulating differentiation and lipid synthesis in keratinocytes. Oat (Avena sativa) has long been used as a soothing agent to relieve skin irritations, and the clinical benefits of topical oat formulations have been proven; however, theRead More
Oxysterols are agonist ligands of RORγt and drive Th17 cell differentiation
ABSTRACT The RAR-related orphan receptor gamma t (RORγt) is a nuclear receptor required for generating IL-17–producing CD4+ Th17 T cells, which are essential in host defense and may play key pathogenic roles in autoimmune diseases. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol and lipid metabolism. Here, we describe the identification of several naturally occurringRead More
Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil
ABSTRACT Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. In the present studies, the effects of oil rich in EPA on gene expression and activation of nuclear receptors was examined and compared with other 3-PUFAs. The EPA-rich oil (EO) altered the expression of FA metabolism genes in THP-1 cells, including stearoylRead More
Eating competence is related to PPARβ/d and PGC-1a genotypes
ABSTRACT PPARa L162A, PPARg 12A, PPARβ/d rs226766 , and PGC-1a G482S genotype distributions were compared with TFEQ-R18 and ecSI scores; responses were gender-specific and paralleled published values. Results confirmed less emotional eating (EE) (P<.001), cognitive restraint (CR) (P<.001) and uncontrolled eating (UE) (P=.1) with EC (ecSI score >= 32). Subjects in the lowest ecSI tertileRead More
Differential Activation of Nuclear Receptors by Perflunoriated Fatty Acid Analogs and Natural Fatty Acids: A Comparison of Human, Mouse, and Rat Peroxisome Proliferator-Activated Receptor Receptor-a, -b, and -c, Liver X Receptor-b, and Retinoid X Receptor-a
ABSTRACT Administration of ammonium salts of perfluorooctanoate (PFOA) to rats results in peroxisome proliferation and benign liver tumors, events associated with activation of the nuclear receptor (NR) peroxisome proliferator-activated receptor-a (PPARa). Due to its fatty acid structure, PFOA may activate other NRs, such as PPARb, PPARg, liver X receptor (LXR), or retinoid X receptor (RXR). In this study, theRead More