Abstract
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.
Highlights
IntroductionThere is no report whether AMPK and stress kinases activities in PBMCs will be altered between lean, overweight and obese subjects and the potential link between metabolic stress and altered Mitogen-activated protein kinases (MAPKs) signaling in PBMCs is unclear
Body weight, BMI, waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), systolic blood pressure (SBP), as well as plasma TG, cholesterol, LDL-C and insulin were significantly higher in the OW and OB group compared to the lean group
Plasma glucose and NEFAs were significantly higher in the OB group compared to the lean group
Summary
There is no report whether AMPK and stress kinases activities in PBMCs will be altered between lean, overweight and obese subjects and the potential link between metabolic stress and altered MAPKs signaling in PBMCs is unclear. ER stress has been recognized as a key mechanism involved in obesity related pathologies[11] It remains unknown what might be critical factors for elevated ER stress markers under obese condition. The aim of the present study is 1) to determine whether there are differences for stress kinases related signaling pathways, ER stress, inflammation and AD related markers (i.e. APP, PS1 and PS2) in PBMCs from Chinese middle-aged men with varied body mass index (BMI); and 2) whether high glucose and fatty acids (FFAs) might be critical factors for affecting ER stress and AD markers under obese condition
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