title: High calorie diet triggers hypothalamic angiopathy.
abstract: Obesity, type 2 diabetes, and related diseases represent major health threats to modern society. Related pathophysiology of impaired neuronal function in hypothalamic control centers regulating metabolism and body weight has been dissected extensively and recent studies have started focusing on potential roles of astrocytes and microglia. The hypothalamic vascular system, however, which maintains the microenvironment necessary for appropriate neuronal function, has been largely understudied. We recently discovered that high fat/high sucrose diet exposure leads to increased hypothalamic presence of immunoglobulin G (IgG1). Investigating this phenomenon further, we have discovered a significant increase in blood vessel length and density in the arcuate nucleus (ARC) of the hypothalamus in mice fed a high fat/high sucrose diet, compared to matched controls fed standard chow diet. We also found a clearly increased presence of α-smooth muscle actin immunoreactive vessels, which are rarely present in the ARC and indicate an increase in the formation of new arterial vessels. Along the blood brain barrier, an increase of degenerated endothelial cells are observed. Moreover, such hypothalamic angiogenesis was not limited to rodent models. We also found an increase in the number of arterioles of the infundibular nucleus (the human equivalent of the mouse ARC) in patients with type 2 diabetes, suggesting angiogenesis occurs in the human hypothalamus of diabetics. Our discovery reveals novel hypothalamic pathophysiology, which is reminiscent of diabetic retinopathy and suggests a potential functional involvement of the hypothalamic vasculature in the later stage pathogenesis of metabolic syndrome.
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment & Technical University Munich, Munich, Germany.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yi
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
authors.forename: Martin
authors.initials: M
authors.lastname: Krüger
authors.forename: Anneke
authors.initials: A
authors.lastname: Alkemade
authors.forename: Dhiraj G
authors.initials: DG
authors.lastname: Kabra
authors.forename: Sophie
authors.initials: S
authors.lastname: Hanske
authors.forename: Jessica
authors.initials: J
authors.lastname: Filosa
authors.forename: Paul
authors.initials: P
authors.lastname: Pfluger
authors.forename: Nathan
authors.initials: N
authors.lastname: Bingham
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: James
authors.initials: J
authors.lastname: Herman
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
authors.forename: Marcus
authors.initials: M
authors.lastname: Baumann
authors.forename: Richard
authors.initials: R
authors.lastname: Lang
authors.forename: Javier E
authors.initials: JE
authors.lastname: Stern
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
keywords: Blood brain barrier; Capillary; Diabetes; Endothelial cell; Fluorescent angiography; Obesity
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