Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice

The consumption of saturated fatty acids is one of the leading risk factors for Alzheimer's Disease (AD) development. Indeed, the short-term consumption of a high-fat diet (HFD) is related to increased inflammatory signals in the hippocampus; however, the potential molecular mechanisms linking it to AD pathogenesis are not fully elucidated. In our study, we investigated the effects of short-term HFD feeding (within 3, 7 and 10 days) in AD markers and neuroinflammation in the hippocampus of mice. The short period of HFD increased fasting glucose and HOMA-IR. Also, mice fed HFD increased the protein content of beta-Amyloid, pTau, TNF alpha, IL1 beta, pJNK, PTP1B, peIF2 alpha, CHOP, Caspase3, Cleaved-Caspase3 and Alzheimer-related genes (Bax, PS1, PEN2, Aph1b). At 10 days, both neuronal (N2a) and microglial (BV2) cells presented higher expression of inflammatory and apoptotic genes when stimulated with palmitate. These findings suggest that a short period of consumption of a diet rich in saturated fat is associated with activation of inflammatory, ER stress and apoptotic signals in the hippocampus of young mice79284293COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP306535/2017-3; 309339/2016-2; 462410/2014-52016/18488-8Obesity and Comorbidities Research Center - OCRC; CNPqNational Council for Scientific and Technological Development (CNPq) [306535/2017-3, 309339/2016-2, 462410/2014-5]; FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/18488-8