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Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer's disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels


, : Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer's disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels. Alzheimer's & Dementia 12(8): 851-861

Epidemiologic studies have demonstrated an association between diabetes and dementia. Insulin signaling within the brain, in particular within the hypothalamus regulates carbohydrate, lipid, and branched chain amino acid (BCAA) metabolism in peripheral organs such as the liver and adipose tissue. We hypothesized that cerebral amyloidosis impairs central nervous system control of metabolism through disruption of insulin signaling in the hypothalamus, which dysregulates glucose and BCAA homeostasis resulting in increased susceptibility to diabetes. We examined whether APP/PS1 mice exhibit increased susceptibility to aging or high-fat diet (HFD)-induced metabolic impairment using metabolic phenotyping and insulin-signaling studies. APP/PS1 mice were more susceptible to high-fat feeding and aging-induced metabolic dysregulation including disrupted BCAA homeostasis and exhibited impaired hypothalamic insulin signaling. Our data suggest that AD pathology increases susceptibility to diabetes due to impaired hypothalamic insulin signaling, and that plasma BCAA levels could serve as a biomarker of hypothalamic insulin action in patients with AD.

US$19.90

PMID: 26928090

DOI: 10.1016/j.jalz.2016.01.008


Other references

de los Reyes-Gavilán, C.G.; Fernández, Mía.; Hudson, J.Andrew.; Korpela, R., 2015: Role of microorganisms present in dairy fermented products in health and disease. Biomed Research International 2015: 204173-204173

Preta, G., 2017: Understanding the Dr. Jekyll and Mr. Hyde nature of apoptosis-inducing factor: future perspectives. Apoptosis-inducing factor (AIF) is emerging as a key protein in regulation of basic physiological processes including phagocytosis, mitophagy and regulation of the redox state. Recent evidences suggest that the enzymatic activity of AIF may play a...

Santarelli, M.F.; Landini, L.; Lombardi, M.; Positano, V.; L'Abbate, A.; Benassi, A., 2001: A model-based method for myocardium flow estimation. Magma 11(1-2): 87-88

Davis, D.P.; Poste, J.C.; Kelly, D., 2005: The UCSD Research Associate Program: a recipe for successfully integrating undergraduates with emergency medicine research. Previous reports have documented the successful integration of undergraduates into the Emergency Department (ED) to assist in data collection for various research projects, with resultant improvements in departmental academic productivity. These r...

Tang, S.X.; Sun, Y.H.; Xu, Y.; Zhou, X.R.; Yang, W.T., 2016: Clinicopathologic study of seromucinous carcinoma of ovary. NlmCategory="UNASSIGNED"><b>Objective:</b> To elucidate the clinicopathologic characteristics, immunophenotype and differential diagnosis of ovarian seromucinous carcinoma. <b>Methods:</b> The clinical and path...

Hosoi, S.; Fukami, T.; Tsuji, A.; Hiyoshi, M., 1999: Method and apparatus for detecting denaturation of nucleic acid. Official Gazette of the United States Patent & Trademark Office Patents 1218(3): 2137-2138, Jan 19

Wilson T.P.; Kroger M., 1982: Evaluation of sodium omadine as a new milk sample preservative. Journal of Dairy Science 65(SUPPL 1): 73

Hutchinson, S.; Wordsworth, B.P.; Handford, P.A., 2001: Marfan syndrome caused by a mutation in FBN1 that gives rise to cryptic splicing and a 33 nucleotide insertion in the coding sequence. We have studied a patient with Marfan syndrome whose mutation was not detected by heteroduplex analysis. Primary cultured patient fibroblasts were metabolically labelled and found to secrete fibrillin-1 defectively when compared with an age-matche...

Ribeiro, F.; Cowx, I.G.; Tiago, P.; Filipe, A.F.; Moreira D.C.sta, L.; Collares Pereira, M.J., 2003: Growth and reproductive traits of diploid and triploid forms of the Squalius alburnoides cyprinid complex in a tributary of the Guadiana River, Portugal. The Squalius alburnoides hybrid complex has diploid, triploid and some rare tetraploid male and female forms, with triploid females predominating in most populations. The reproductive traits of diploids and triploids from a population in a tributa...

Vogl, T.J.; Hinrichs, T.; Jacobi, V.; Böhme, A.; Hoelzer, D., 2000: Computed tomographic appearance of pulmonary mucormycosis. Analysis of the morphological characteristics of pulmonary mucormycosis using computed tomography (CT). Prospective analysis of CT studies in 9 patients out of 19 patients with proven pulmonary mucormycosis. Pulmonary mucormycosis was most frequen...