High calorie diet triggers hypothalamic angiopathy

Chun Xia Yi, Martin Gericke, Martin Krüger, Anneke Alkemade, Dhiraj G. Kabra, Sophie Hanske, Jessica Andrea Filosa, Paul Pfluger, Nathan Bingham, Stephen C. Woods, James Herman, Andries Kalsbeek, Marcus Baumann, Richard Lang, Javier Eduardo Stern, Ingo Bechmann, Matthias H. Tschöp

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalMolecular Metabolism
Volume1
Issue number1-2
DOIs
StatePublished - Dec 1 2012

Fingerprint

Arcuate Nucleus of Hypothalamus
Diet
High Fat Diet
Type 2 Diabetes Mellitus
Blood Vessels
Sucrose
Immunoglobulin G
Microglia
Arterioles
Diabetic Retinopathy
Blood-Brain Barrier
Astrocytes
Hypothalamus
Smooth Muscle
Actins
Rodentia
Endothelial Cells
Obesity
Body Weight
Health

Keywords

  • Blood brain barrier
  • Capillary
  • Diabetes
  • Endothelial cell
  • Fluorescent angiography
  • Obesity

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yi, C. X., Gericke, M., Krüger, M., Alkemade, A., Kabra, D. G., Hanske, S., ... Tschöp, M. H. (2012). High calorie diet triggers hypothalamic angiopathy. Molecular Metabolism, 1(1-2), 95-100. https://doi.org/10.1016/j.molmet.2012.08.004

High calorie diet triggers hypothalamic angiopathy. / Yi, Chun Xia; Gericke, Martin; Krüger, Martin; Alkemade, Anneke; Kabra, Dhiraj G.; Hanske, Sophie; Filosa, Jessica Andrea; Pfluger, Paul; Bingham, Nathan; Woods, Stephen C.; Herman, James; Kalsbeek, Andries; Baumann, Marcus; Lang, Richard; Stern, Javier Eduardo; Bechmann, Ingo; Tschöp, Matthias H.

In: Molecular Metabolism, Vol. 1, No. 1-2, 01.12.2012, p. 95-100.

Research output: Contribution to journalArticle

Yi, CX, Gericke, M, Krüger, M, Alkemade, A, Kabra, DG, Hanske, S, Filosa, JA, Pfluger, P, Bingham, N, Woods, SC, Herman, J, Kalsbeek, A, Baumann, M, Lang, R, Stern, JE, Bechmann, I & Tschöp, MH 2012, 'High calorie diet triggers hypothalamic angiopathy', Molecular Metabolism, vol. 1, no. 1-2, pp. 95-100. https://doi.org/10.1016/j.molmet.2012.08.004
Yi CX, Gericke M, Krüger M, Alkemade A, Kabra DG, Hanske S et al. High calorie diet triggers hypothalamic angiopathy. Molecular Metabolism. 2012 Dec 1;1(1-2):95-100. https://doi.org/10.1016/j.molmet.2012.08.004
Yi, Chun Xia ; Gericke, Martin ; Krüger, Martin ; Alkemade, Anneke ; Kabra, Dhiraj G. ; Hanske, Sophie ; Filosa, Jessica Andrea ; Pfluger, Paul ; Bingham, Nathan ; Woods, Stephen C. ; Herman, James ; Kalsbeek, Andries ; Baumann, Marcus ; Lang, Richard ; Stern, Javier Eduardo ; Bechmann, Ingo ; Tschöp, Matthias H. / High calorie diet triggers hypothalamic angiopathy. In: Molecular Metabolism. 2012 ; Vol. 1, No. 1-2. pp. 95-100.
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