A TRbeta-selective agonist confers resistance to diet-induced obesity.
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.
Amorim
Beatriz S
BS
Biological Science Course, CCBS, Presbyterian University Mackenzie, Rua da Consolação, 930 Prédio 38, Curso de Biologia, São Paulo, SP 01302-907, Brazil.
Ueta
Cintia B
CB
Freitas
Beatriz C G
BC
Nassif
Renata J
RJ
Gouveia
Cecília Helena de Azevedo
CH
Christoffolete
Marcelo A
MA
Moriscot
Anselmo S
AS
Lancelloti
Carmen Lucia
CL
Llimona
Flávia
F
Barbeiro
Hermes Vieira
HV
de Souza
Heraldo Possolo
HP
Catanozi
Sergio
S
Passarelli
Marisa
M
Aoki
Marcelo S
MS
Bianco
Antonio C
AC
Ribeiro
Miriam O
MO
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
D000085:Acetates; D001559:Benzhydryl Compounds; D004041:Dietary Fats; C483767:GC 24 compound; D015850:Interleukin-6; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D002784:Cholesterol