title: The lateral hypothalamus: a site for integration of nutrient and fluid balance.
abstract: This paper reviews seemingly obligatory relations between nutrient and fluid balance. A relatively novel neuronal pathway involving interplay between acetylcholine and the melanocortins, αMSH and AGRP in the arcuate nucleus (Arc) of the hypothalamus projecting to the lateral hypothalamus (LH) may bridge this gap. In the fasted condition, increased expression of MCH (due to muscarinic-3 receptor stimulation and low melanocortin tone) and neuronal release of MCH (via Orexin signaling) underlies a drive towards positive energy balance, increased B cell capacity to secrete insulin, and this is associated with optimal fluid homeostasis. A hypohydrated state is hypothesized to yield downregulation of leptin signaling (potentially via inhibitory effects of osmotic stress on mTOR), but osmotic stress may prevent MCH expression via the OVLT-SFO complex. If this occurs in an obese state, impaired pancreatic B cell capacity and peripheral insulin insensitivity as a result of hypohydration may underlie cardio-metabolic diseases.
authors.affiliation: Center for Behavior and Neurosciences, Unit of Neuroendocrinology, University of Groningen, The Netherlands. gertjan.van.dijk@rug.nl
authors.forename: Gertjan
authors.initials: G
authors.lastname: van Dijk
authors.forename: Simon S
authors.initials: SS
authors.lastname: Evers
authors.forename: Stefano
authors.initials: S
authors.lastname: Guidotti
authors.forename: Simon N
authors.initials: SN
authors.lastname: Thornton
authors.forename: Anton J W
authors.initials: AJ
authors.lastname: Scheurink
authors.forename: Csaba
authors.initials: C
authors.lastname: Nyakas
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D054369:Agouti-Related Protein / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D002799:Cholinergic Fibers / Q000502:physiology; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D007028:Hypothalamic Hormones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008954:Models, Biological; D009434:Neural Pathways / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009747:Nutritional Physiological Phenomena / Q000502:physiology*; D000068797:Orexins; D010907:Pituitary Hormones / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*; D000521:alpha-MSH / Q000502:physiology
chemical_list: D054369:Agouti-Related Protein; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D000521:alpha-MSH; C019463:melanin-concentrating hormone; D000109:Acetylcholine