GABA type B receptor signaling in proopiomelanocortin neurons protects against obesity, insulin resistance, and hypothalamic inflammation in male mice on a high-fat diet.

There is evidence suggesting that the GABA system in the arcuate nucleus, where orexigenic neuropeptide Y and agouti-related peptide as well as anorexigenic proopiomelanocortin (POMC) are expressed, plays an important role in energy balance. In this study, we generated POMC-specific GABAB receptor-deficient [knock-out (KO)] mice. Male KO mice on a high-fat diet (HFD) showed mild increases in body weight (BW) at the age of 9 weeks compared to wild-type (WT) mice, and the differences remained significant until 16 weeks old.

Lesion of area postrema attenuated hyperphagic responses to glucoprivation, but not transcriptional activation of the neuropeptide Y gene in rats.

The area postrema (AP) is a circumventricular organ that lacks a blood-brain barrier. Previous studies have shown that the lesion of AP (APX) attenuated hyperphagic responses to glucoprivation. As the orexigenic neuropeptide Y (NPY) neurons have been implicated in the regulation of food intake, we examined whether the activation of NPY neurons by glucoprivation is mediated through the AP as well.

TNFα increases hypothalamic PTP1B activity via the NFκB pathway in rat hypothalamic organotypic cultures.

In obesity, levels of tumor necrosis-factor α (TNFα) are well known to be elevated in adipose tissues or serum, and a high-fat diet (HFD) reportedly increases TNFα expression in the hypothalamus. The expression levels of hypothalamic protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin and insulin signaling, are also elevated by HFD, and several lines of evidence support a relationship between TNFα and PTP1B. It remains unclear however how TNFα acts locally in the hypothalamus to regulate hypothalamic PTP1B expression and activity.

Repeated glucoprivation delayed hyperphagic responses while activating neuropeptide Y neurons in rats.

It is well known that glucoprivation induces the release of counterregulatory hormones such as glucagon, and that the response is attenuated when the stimuli are repeated. Glucoprivation also activates orexigenic neurons and induces hyperphagic responses, although it remains unclear whether these responses are attenuated in repeated glucoprivation. In this study, we examined time course changes in feeding as well as activities of orexigenic neuropeptide Y (NPY) neurons in repeated glucoprivation in rats.

Glucocorticoids increase NPY gene expression in the arcuate nucleus by inhibiting mTOR signaling in rat hypothalamic organotypic cultures.

The mammalian target of rapamycin (mTOR) has been implicated in the regulation of physiological functions such as cell growth and proliferation, and glucocorticoids reportedly inhibit mTOR signaling in peripheral tissues. Recent studies suggest that the mTOR signaling in the hypothalamus plays a critical role in maintaining energy homeostasis. In this study, we examined whether the mTOR signaling in the hypothalamus is involved in the regulation of neuropeptide Y (Npy) gene expression in the arcuate nucleus by glucocorticoids.

The medial hypothalamus is required for the feeding response to glucoprivation but not to food deprivation.

While the hypothalamus has been implicated in the regulation of energy balance, the central mechanisms and neural circuit that coordinate the feeding response to energy deficit have not been fully clarified. To better understand the role of the hypothalamus in mediating hyperphagic responses to food deprivation or glucoprivation, we examined the feeding responses in rats in which the medial hypothalamus (MH) was isolated from the rest of the brain. The isolation of the MH was performed with a Halasz's knife cut, and experiments were performed 7 days after the operation.