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

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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Kublaoui BM,Holder JL Jr,Tolson KP,Gemelli T,Zinn AR

doi

10.1210/en.2006-0453

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

4542-9

issue

10

eissn

0013-7227

issn

1945-7170

pii

en.2006-0453

journal_volume

147

pub_type

杂志文章