Alhusaini, S. (Saif), McGee, K. C. (Kirsty Claire), Harte, A. L. (Alison L.), McTernan, P. G. (Philip G.), Kumar, Sudhesh and Tripathi, G. (Gyanendra). (2010) Lipopolysaccharide, high glucose and saturated fatty acids induce endoplasmic reticulum stress in cultured primary human adipocytes : salicylate alleviates this stress. Biochemical and Biophysical Research Communications, Vol.397 (No.3). pp. 472-478. ISSN 0006-291X

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Abstract

Recent findings indicate that endoplasmic reticulum (ER) stress is significantly increased in adipose tissue of obese human subjects and is critical to the initiation and integration of pathways of inflammation and insulin action. But the factors inducing ER stress in human adipose tissue are unknown. The common factors increased in obesity and linked to insulin resistance are hyperglycaemia, hyperlipidemia and also endotoxemia. Therefore, our aims were to investigate: (1) the role of lipopolysaccharide (LPS), high glucose (HG) and saturated fatty acids (SFA) as inducers of ER stress in primary human adipocytes and (2) whether salicylate, a known anti-inflammatory compound, can alleviate this effect. Components of the ER stress pathways were studied in human abdominal subcutaneous (AbSc) adipose tissue (AT) from obese and lean. Following the culture and differentiation of primary human preadipocytes, these adipocytes were treated with LPS, HG, tunicamycin (Tun) and SFA either alone or in combination with sodium salicylate (Sal). Markers of ER stress were significantly increased in AbSc AT of obese. Differentiated human adipocytes treated with LPS, Tun, HG and SFA showed significant activation of eukaryotic translation initiation factor 2 alpha, (eIF2 alpha) and activating transcription factor 6 (ATF6) and their down-stream targets. Sal alleviated this effect and activated AktSer473 phosphorylation. This study presents important evidence that: (1) there is increased ER stress in adipose tissue of obese individuals, (2) LPS, hyperglycaemia and saturated fatty acids induce significant ER stress in primary human adipocytes and (3) this induction is alleviated by salicylate.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Adipose tissues, Endoplasmic reticulum, Obesity
Journal or Publication Title:	Biochemical and Biophysical Research Communications
Publisher:	Academic Press Inc. Elsevier Science
ISSN:	0006-291X
Date:	2 July 2010
Volume:	Vol.397
Number:	No.3
Number of Pages:	7
Page Range:	pp. 472-478
Identification Number:	10.1016/j.bbrc.2010.05.138
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Research Councils UK (RCUK), United Arab Emirates, British Heart Foundation
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URI:	http://wrap.warwick.ac.uk/id/eprint/5558

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