Stress kinases, endoplasmic reticulum stress, and Alzheimer’s disease related markers in peripheral blood mononuclear cells from subjects with increased body weight

• Published in: Scientific reports Vol. 6; no. 1; p. 30890
• Main Authors: Lei, Ting, Yu, Lugang, Qin, Liqiang, Xu, Baohui, Zhou, Lingmei, Cheng, Jinbo, Zhou, Hui, Pang, Xing, Wan, Zhongxiao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.08.2016; Nature Publishing Group
• Subjects: 631/443/319/1642; 692/163/2743/393; 96/2; 96/21; 96/95; AKT protein; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer Disease - etiology; Alzheimer's disease; Biomarkers - blood; Body Mass Index; Body weight; Caspase; Caspase-3; CCR2 protein; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Fatty acids; Gene expression; Glucose; Heat-Shock Proteins - blood; Humanities and Social Sciences; Humans; Inflammation; Inflammation - blood; Inflammation - diagnosis; Inflammation - etiology; JNK protein; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Male; Metabolism; Middle Aged; Monocyte chemoattractant protein 1; multidisciplinary; Neurodegenerative diseases; Obesity; Obesity - complications; Overweight; Peripheral blood mononuclear cells; Phosphorylation; Presenilin 1; Presenilin 2; Prognosis; Protein expression; Science; Science (multidisciplinary); Serine; TLR2 protein; TLR4 protein; Toll-like receptors; Transcription Factor CHOP - blood; X-Box Binding Protein 1 - blood
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30890

We aimed to characterize endoplasmic reticulum stress, inflammation, and Alzheimer’s disease (AD) related markers in peripheral blood mononuclear cells (PBMCs) from males with varied BMI; and to explore whether high glucose and fatty acids (FFAs) might be critical factors for inducing metabolic alterations in PBMCs under obese condition. Approximately 45 middle-aged men were enrolled with varied BMI. At the protein expression level, compared to the lean, the phosphorylation of AMPK, and p-Akt at serine 473 were significantly reduced from the overweight (OW) and/or obese (OB); while the protein expression of p-JNK, cleaved caspase 3, CHOP and p-eIF2α were elevated from the OW and/or OB. At the mRNA expression level, ER stress markers (i.e. GRP78, CHOP and XBP-1), inflammatory markers (i.e.TLR2, TLR4 and CCR2) and AD markers (i.e. APP, PS1 and PS2) were significantly higher in PBMCs from OB compared to lean. In cultured PBMCs, high glucose and FFAs induced GRP78, CHOP and XBP-1 mRNA, and high glucose also induced APP, PS1 and PS2 mRNA. In conclusion, altered markers including AMPK, ER stress and AD related makers under obese condition could be easily obtained from PBMCs. These markers might provide new mechanistic links between obesity and other metabolic complications including AD.