Neuronal Lipoprotein Lipase Deficiency Alters Neuronal Function and Hepatic Metabolism.

The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism.

Acute Lesioning and Rapid Repair of Hypothalamic Neurons outside the Blood-Brain Barrier.

Neurons expressing agouti-related protein (AgRP) are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB), allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRP) were rapidly ablated by peripheral administration of monosodium glutamate (MSG), whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC) neurons were spared.

Leptin potentiates astrogenesis in the developing hypothalamus.

Background: The proper establishment of hypothalamic feeding circuits during early development has a profound influence on energy homeostasis, and perturbing this process could predispose individuals to obesity and its associated consequences later in life. The maturation of hypothalamic neuronal circuitry in rodents takes place during the initial postnatal weeks, and this coincides with a dramatic surge in the circulating level of leptin, which is known to regulate the outgrowth of key neuronal projections in the maturing hypothalamus. Coincidently, this early postnatal period also marks the rapid proliferation and expansion of astrocytes in the brain.

Loss of protein tyrosine phosphatase N2 potentiates epidermal growth factor suppression of intestinal epithelial chloride secretion.

The Crohn's disease candidate gene, protein tyrosine phosphatase nonreceptor type 2 (PTPN2), has been shown to regulate epidermal growth factor (EGF)-induced phosphatidylinositol 3-kinase (PI3K) activation in fibroblasts. In intestinal epithelial cells (IECs), EGF-induced EGF receptor (EGFR) activation and recruitment of PI3K play a key role in regulating many cellular functions including Ca(2+)-dependent Cl(-) secretion. Moreover, EGFR also serves as a conduit for signaling by other non-growth factor receptor ligands such as the proinflammatory cytokine, IFN-γ.