Early effects of high-fat diet on hypothalamic cell proliferation

The hypothalamus is one of the main brain structure involved in the control of. energy homeostasis. Recent reports indicate that hypothalamus exhibits neuroproliferative. potency in adult. Moreover, it has been found that hypothalamic cell. proliferation could be modulated by numerous intrinsic factors such as CNTF, IGF-. 1, bFGF and EGF, and by external and internal conditions such as dehydration,. variation in ambient temperature and during ovarian cycle. Interestingly, experimental. manipulation of neurogenesis can affect body weight. However, whether. nutritional conditions could influence hypothalamic cell proliferation and thereby. modify energy homeostasis is still unknown. To address this question, mice were. subjected to a high fat diet (HFD) for 1 week and hypothalamic cell renewal was. assessed through central chronic infusion of Bromodeoxy-Uridine (BrdU). Using this. approach, we report that hypothalamus constitutively exhibits G2000 BrdUpositive. neo-formed cells per day. This proliferative rate was significantly higher in hypothalamus 3 days after the onset of HFD (+60%) but decreased by 50% on day. 5. To determine whether these HFD-induced modifications of cell renewal were. linked to change in cell proliferation, we counted Ki67 immunoreactive cells. We. found 1937 Ki67 immunoreactive cells in hypothalamus from mice fed with. standard chow. However, the number of such cell was significantly higher in mice. fed with HFD for 1 and 3 days (+30% and 50%, respectively), and returned to basal. value after 5 days. In order to evaluate the role of newborn cells, HFD fed mice were. treated with the anti-mitotic arabinoside cytosine (AraC) for 30 days. Results show. that AraC treatment increased HFD-induced body weight gain, suggesting that. newborn HFD-induced cells produce anorectic function. Altogether these data. demonstrate that a change in diet induces cell proliferation in the hypothalamus. which might be involved in the control of long-term energy homeostasis.