The reduction in baseline energy expenditure observed in these mice was accompanied by a reduction in activity. In post-injection mice, we observed a strong inverse correlation between the degree of obesity and hypothalamic Sim1 expression.
Compared to controls, mice with Sim1 neuron ablation became obese (with increased fat mass) on a chow diet due to increased food intake and reduced energy expenditure. In these mice, Sim1 neuron ablation was performed by intracerebroventricular (ICV) injection of diphtheria toxin. In this study, Sim1cre mice were bred to homozygous inducible diphtheria toxin receptor (iDTR) mice to generate mice expressing the simian DTR in Sim1 cells. It remains unknown whether Sim1 neurons regulate energy expenditure. Bilateral ablation of the PVH causes obesity due to hyperphagia and reduced energy expenditure. Previously we showed that Sim1 +/− mice and conditional postnatal Sim1 −/− mice exhibit hyperphagia, obesity, increased linear growth and susceptibility to diet-induced obesity, but no decrease in energy expenditure. This nucleus is a critical regulator of appetite, energy expenditure and body weight. Single-minded 1 (Sim1) is a transcription factor necessary for development of the paraventricular nucleus of the hypothalamus (PVH).
