Back to Search
Start Over
Impaired metabolic effects of a thyroid hormone receptor beta-selective agonist in a mouse model of diet-induced obesity
- Source :
- Thyroid : official journal of the American Thyroid Association. 20(5)
- Publication Year :
- 2010
-
Abstract
- The use of selective agonists of the thyroid hormone receptor isoform beta (TRbeta) has been linked to metabolic improvement in animal models of diet-induced obesity, nonalcoholic liver disease, and genetic hypercholesterolemia.To identify potential target tissues of such compounds, we exposed primary murine brown adipocytes and skeletal myocytes for 24 hours to 50 nM GC-24, a highly selective TRbeta agonist. GC-24 (17 ng/[g BW.day] for 36 days) was also tested in a mouse model of diet-induced obesity.While the brown adipocytes responded to GC-24, with 17%-400% increases in the expression of 12 metabolically relevant genes, the myocytes remained largely unresponsive to GC-24 treatment. In control mice kept on chow diet, GC-24 treatment accelerated energy expenditure by about 15% and limited body weight gain by about 50%. However, in the obese animals the GC-24-mediated reduction in body weight gain dropped to only 20%, while energy expenditure remained unaffected. In addition, an analysis of gene expression in the skeletal muscle, brown adipose tissue, and liver of these obese animals failed to identify a conclusive GC-24 transcriptome footprint.Feeding a high-fat diet impairs most of the beneficial metabolic effects associated with treatment with TRbeta-selective agonists.
- Subjects :
- Agonist
Male
medicine.medical_specialty
medicine.drug_class
Endocrinology, Diabetes and Metabolism
Muscle Fibers, Skeletal
Gene Expression
Biology
Acetates
Thyroid hormone receptor beta
chemistry.chemical_compound
Mice
Endocrinology
Anti-Obesity Agents
Internal medicine
medicine
Myocyte
Animals
Benzhydryl compounds
Obesity
RNA, Messenger
Benzhydryl Compounds
Cells, Cultured
Thyroid hormone receptor
Triiodothyronine
Body Weight
Calorimetry, Indirect
Thyroid Hormone Receptors beta
Organ Size
medicine.disease
Diet
Mice, Inbred C57BL
Adipocytes, Brown
Metabolism
chemistry
Energy Metabolism
Original Studies, Reviews, and Scholarly Dialog
Subjects
Details
- ISSN :
- 15579077
- Volume :
- 20
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Thyroid : official journal of the American Thyroid Association
- Accession number :
- edsair.doi.dedup.....8449d5069e8d9c8e35c8ee7f33789fa1