SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake
| Autor: | Kristen P. Tolson, Bassil M. Kublaoui, Terry Gemelli, Andrew R. Zinn, J. Lloyd Holder |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Genetically modified mouse medicine.medical_specialty Pro-Opiomelanocortin Genotype Transgene Mice Transgenic Growth Hyperphagia Biology Eating Mice Endocrinology Melanocortin receptor Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Animals Humans Obesity Transgenes Reverse Transcriptase Polymerase Chain Reaction digestive oral and skin physiology Diet Mice Inbred C57BL Repressor Proteins Melanocortin 4 receptor alpha-MSH Knockout mouse Body Composition SIM1 Receptor Melanocortin Type 4 Female Melanocortin Energy Metabolism Haploinsufficiency |
| Zdroj: | Endocrinology. 147:4542-4549 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2006-0453 |
| Popis: | Single-minded 1 (SIM1) mutations are associated with obesity in mice and humans. Haploinsufficiency of mouse Sim1 causes hyperphagic obesity with increased linear growth and enhanced sensitivity to a high-fat diet, a phenotype similar to that of agouti yellow and melanocortin 4 receptor knockout mice. To investigate the effects of increased Sim1 dosage, we generated transgenic mice that overexpress human SIM1 and examined their phenotype. Compared with wild-type mice, SIM1 transgenic mice had no obvious phenotype on a low-fat chow diet but were resistant to diet-induced obesity on a high-fat diet due to reduced food intake with no change in energy expenditure. The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated. Our results indicate that the melanocortin 4 receptor signals through Sim1 or its transcriptional targets in controlling food intake but not energy expenditure. |
| Databáze: | OpenAIRE |
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