SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake

Bassil M. Kublaoui, J. Lloyd Holder, Kristen P. Tolson, Terry Gemelli, Andrew R. Zinn

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4542-4549
Number of pages8
JournalEndocrinology
Volume147
Issue number10
DOIs
Publication statusPublished - 2006

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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