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Thyroid Transcription Factor-1 Regulates Feeding Behavior via Melanocortin Pathway in the Hypothalamus
- Source :
- Diabetes
- Publication Year :
- 2011
- Publisher :
- American Diabetes Association, 2011.
-
Abstract
- OBJECTIVE α-Melanocyte–stimulating hormone (α-MSH) and agouti-related peptide (AgRP) control energy homeostasis by their opposing actions on melanocortin receptors (MC3/4R) in the hypothalamus. We previously reported that thyroid transcription factor-1 (TTF-1) controls feeding behavior in the hypothalamus. This study aims to identify the function of TTF-1 in the transcriptional regulation of AgRP and α-MSH synthesis for the control of feeding behavior. RESEARCH DESIGN AND METHODS TTF-1 activity in AgRP and pro-opiomelanocortin (POMC) transcription was examined using gel-shift and promoter assays and an in vivo model of TTF-1 synthesis inhibition by intracerebroventricular injection of an antisense (AS) oligodeoxynucleotide (ODN). Double immunohistochemistry was performed to colocalize TTF-1 and AgRP or α-MSH in the hypothalamic arcuate nucleus (ARC). To determine whether TTF-1 action on food intake is mediated through MC3/4R, we measured changes in food intake upon intracerebroventricular injection of MC3/4R antagonists (SHU9119 and AgRP) into rat brain preinjected with the AS ODN. RESULTS TTF-1 stimulated AgRP but inhibited POMC transcription by binding to the promoters of these genes. TTF-1 was widely distributed in the hypothalamus, but we identified some cells coexpressing TTF-1 and AgRP or α-MSH in the ARC. In addition, intracerebroventricular administration of leptin decreased TTF-1 expression in the hypothalamus, and AS ODN-induced inhibition of TTF-1 expression decreased food intake and AgRP expression but increased α-MSH expression. Anorexia induced by the AS ODN was attenuated by the administration of MC3/4R antagonists. CONCLUSIONS TTF-1 transcriptionally regulates synthesis of AgRP and α-MSH in the ARC and affects feeding behavior via the melanocortin pathway.
- Subjects :
- endocrine system
medicine.medical_specialty
Melanocyte-stimulating hormone
Endocrinology, Diabetes and Metabolism
Blotting, Western
Thyroid Nuclear Factor 1
Thyroid Transcription Factor 1
Electrophoretic Mobility Shift Assay
Biology
Energy homeostasis
Cell Line
Oligodeoxyribonucleotides, Antisense
Eating
Mice
Internal medicine
Internal Medicine
medicine
Animals
Agouti-Related Protein
Melanocyte-Stimulating Hormones
RNA, Messenger
Promoter Regions, Genetic
Transcription factor
Cells, Cultured
In Situ Hybridization
Analysis of Variance
Reverse Transcriptase Polymerase Chain Reaction
Leptin
digestive, oral, and skin physiology
Arcuate Nucleus of Hypothalamus
Nuclear Proteins
Promoter
Feeding Behavior
respiratory system
Immunohistochemistry
Rats
Metabolism
Endocrinology
nervous system
alpha-MSH
Hypothalamus
Melanocortin
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....6f38f96ee2bf60636157ce482f149107