title: A TRbeta-selective agonist confers resistance to diet-induced obesity.
abstract: Thyroid hormone receptor beta (TRbeta also listed as THRB on the MGI Database)-selective agonists activate brown adipose tissue (BAT) thermogenesis, while only minimally affecting cardiac activity or lean body mass. Here, we tested the hypothesis that daily administration of the TRbeta agonist GC-24 prevents the metabolic alterations associated with a hypercaloric diet. Rats were placed on a high-fat diet and after a month exhibited increased body weight (BW) and adiposity, fasting hyperglycemia and glucose intolerance, increased plasma levels of triglycerides, cholesterol, nonesterified fatty acids and interleukin-6. While GC-24 administration to these animals did not affect food ingestion or modified the progression of BW gain, it did increase energy expenditure, eliminating the increase in adiposity without causing cardiac hypertrophy. Fasting hyperglycemia remained unchanged, but treatment with GC-24 improved glucose tolerance by increasing insulin sensitivity, and also normalized plasma triglyceride levels. Plasma cholesterol levels were only partially normalized and liver cholesterol content remained high in the GC-24-treated animals. Gene expression in liver, skeletal muscle, and white adipose tissue was only minimally affected by treatment with GC-24, with the main target being BAT. In conclusion, during high-fat feeding treatment with the TRbeta-selective agonist, GC-24 only partially improves metabolic control probably as a result of accelerating the resting metabolic rate.
authors.affiliation: Biological Science Course, CCBS, Presbyterian University Mackenzie, Rua da Consolação, 930 Prédio 38, Curso de Biologia, São Paulo, SP 01302-907, Brazil.
authors.forename: Beatriz S
authors.initials: BS
authors.lastname: Amorim
authors.forename: Cintia B
authors.initials: CB
authors.lastname: Ueta
authors.forename: Beatriz C G
authors.initials: BC
authors.lastname: Freitas
authors.forename: Renata J
authors.initials: RJ
authors.lastname: Nassif
authors.forename: Cecília Helena de Azevedo
authors.initials: CH
authors.lastname: Gouveia
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Christoffolete
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.forename: Carmen Lucia
authors.initials: CL
authors.lastname: Lancelloti
authors.forename: Flávia
authors.initials: F
authors.lastname: Llimona
authors.forename: Hermes Vieira
authors.initials: HV
authors.lastname: Barbeiro
authors.forename: Heraldo Possolo
authors.initials: HP
authors.lastname: de Souza
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Aoki
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
authors.forename: Miriam O
authors.initials: MO
authors.lastname: Ribeiro
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009765:Obesity / Q000517:prevention & control*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D037042:Thyroid Hormone Receptors beta / Q000819:agonists*; D014284:Triiodothyronine / Q000494:pharmacology; D015430:Weight Gain
chemical_list: D000085:Acetates; D001559:Benzhydryl Compounds; D004041:Dietary Fats; C483767:GC 24 compound; D015850:Interleukin-6; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D002784:Cholesterol