Western diet - from metabolic disturbances to acceleration of glia activation and development of Alzheimer’s disease

• Autorzy: Wieckowska A. , Mietelska-Porowska A. , Wydrych M. , Dlugosz J. , Chutoranski D. , Wojda U.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: A diet enriched in fat, cholesterol, and sugar – called the Western diet (WD) – was shown to induce systemic inflammation, obesity, and metabolic syndrome and results directly and indirectly in an impact on brain structure and function. The WD has not been examined yet in the context of Alzheimer’s disease (AD), characterised by altered cleavage of amyloid precursor protein (APP) and deposits of toxic amyloid. AIM(S): We aimed to verify the hypothesis that WD by inducing metabolic syndrome and systemic inflammation may accelerate brain glia activation events and the onset of AD. METHOD(S): To verify this hypothesis, transgenic mice expressing human APP with Swedish AD-causing mutation (APPswe) were fed with WD from 3rd month of age. These mice were compared to APPswe mice in which systemic inflammation was induced by injection of lipopolysaccharide (LPS) and to untreated APPswe mice. All animal groups were subsequently analysed at the age of 4, 8, and 12‑months by immunohistochemical and immunoblotting analysis. RESULTS: Already one month of WD feeding induces metabolic disturbances including hypercholesterolemia and hyperglycaemia and accelerates the brain pathological events in young APPswe mice. After one month of WD feeding, we observed enhanced astrogliosis, altered profile of microglia activation state, and enhanced cleavage of APP in mice brains. Moreover, we observed obesity, enhanced liver weight, and non-alcoholic fatty liver disease (NAFLD) after 3 months of the WD, which suggest that the WD causes alterations in the brain even earlier than in peripheral organs. CONCLUSIONS: These results suggest that the WD leads to brain neuroinflammation and accelerates the development of AD. Therefore, the WD can be considered as a newly identified common civilian AD risk factor. FINANCIAL SUPPORT: Supported by National Science Center grants: 2014/15/D/NZ4/04361, 2018/29/N/ NZ7/01724.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.XLV

Twórcy

autor

Wieckowska A.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Mietelska-Porowska A.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Wydrych M.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Dlugosz J.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Chutoranski D.

• Institute of Psychiatry and Neurology, Warsaw, Poland

autor

Wojda U.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland