The hypothalamus is an essential brain center that maintains multiple physiological homeostatic processes by modulating pituitary hormone secretions. Two centers (nuclei) of the hypothalamus, the paraventricular and supraoptic nuclei (PVN and SON), contain various hormone-producing neurons. Studies of these hormones have been instrumental to our understanding of endocrine homeostasis, including the maintenance of bodily fluid osmolarity and the balance of energy metabolism. Sitting at the top of this genetic cascade is the Sim1 gene.

The Fan lab found that  dissimilar pairs of genes for a hereditary characteristic (heterozygousity),  at the Sim1 locus causes the animal to develop morbid obesity due to over-feeding. Sim1 heterozygous mice exhibit compromised PVN structure and function, supporting a role for PVN in maintaining energy homeostasis via the regulation of feeding. Interestingly, people with the similar  SIM1 gene also exhibit childhood obesity. The work suggests a new avenue for finding genetic determinants of hormonal regulation.Image courtesy NIH