title: Role of nuclear receptors in lipid dysfunction and obesity-related diseases.
abstract: This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 12 meeting in San Diego, CA. The presentations discussed the roles of a number of nuclear receptors in regulating glucose and lipid homeostasis, the pathophysiology of obesity-related disease states, and the promise associated with targeting their activities to treat these diseases. While many of these receptors (in particular, constitutive androstane receptor and pregnane X receptor) and their target enzymes have been thought of as regulators of drug and xenobiotic metabolism, this symposium highlighted the advances made in our understanding of the endogenous functions of these receptors. Similarly, as we gain a better understanding of the mechanisms underlying bile acid signaling pathways in the regulation of body weight and glucose homeostasis, we see the importance of using complementary approaches to elucidate this fascinating network of pathways. The observation that some receptors, like the farnesoid X receptor, can function in a tissue-specific manner via well defined mechanisms has important clinical implications, particularly in the treatment of liver diseases. Finally, the novel findings that agents that selectively activate estrogen receptor β can effectively inhibit weight gain in a high-fat diet model of obesity identifies a new role for this member of the steroid superfamily. Taken together, the significant findings reported during this symposium illustrate the promise associated with targeting a number of nuclear receptors for the development of new therapies to treat obesity and other metabolic disorders.
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS305, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY40536, USA. hswan@email.uky.edu
authors.forename: Hollie I
authors.initials: HI
authors.lastname: Swanson
authors.forename: Taira
authors.initials: T
authors.lastname: Wada
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Angela
authors.initials: A
authors.lastname: Zampella
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.forename: Ann M
authors.initials: AM
authors.lastname: Thomas
authors.forename: Grace L
authors.initials: GL
authors.lastname: Guo
authors.forename: Ramesh
authors.initials: R
authors.lastname: Narayanan
authors.forename: Muralimohan
authors.initials: M
authors.lastname: Yepuru
authors.forename: James T
authors.initials: JT
authors.lastname: Dalton
authors.forename: John Y L
authors.initials: JY
authors.lastname: Chiang
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D015262:Xenobiotics; D005947:Glucose