Effects of thyroid hormone analogs on lipid metabolism and thermogenesis.
Thyroid hormone affects in a myriad of biological processes such as development, growth, and metabolic control. Triiodothyronine (T3) is the biologically active form of thyroid hormone that acts through nuclear receptors, TRalpha and TRbeta, regulating gene expression. Given that the distribution of these receptors is heterogeneous amongst the different tissues, it is not surprising that some physiological effects of T3 are isoform specific. For example, while TRalpha is the dominant receptor in the brain and skeletal system and mediates most of the synergism between T3 and the sympathetic signaling pathway in the heart, TRbeta is abundant in liver and is probably the isoform that mediates most of the T3 effects on lipid metabolism. Thus, it makes sense to develop compounds that selectively act on either one of the TRs, allowing for the activation of specific T3-dependent pathways. This article reviews the recent progress made in this area, focusing on the physiological effects of compounds that lower serum cholesterol and decrease fat mass, as they spare skeletal muscle and bone masses, as well as the heart. The available studies indicate that achieving selective activation of different TR-mediated pathways is a promising strategy for treating lipid disorders and obesity.
Ribeiro
Miriam O
MO
Ciências Biológicas (CCBS), Universidade Presbiteriana Mackenzie, São Paulo, Brazil. miriamribeiro@mackenzie.br
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D052439:Lipid Metabolism Disorders / Q000188:drug therapy / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D022722:Thermogenesis / Q000187:drug effects*; D037021:Thyroid Hormone Receptors alpha / Q000819:agonists* / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000819:agonists* / Q000378:metabolism; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
C517607:5-(3,5-diiodo-4-(3-isopropyl-4-hydroxyphenoxy)benzyl)imidazolidine-2,4-dione; D000963:Antimetabolites; D006827:Hydantoins; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine