4-hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance

Increased adipose production of 4-hydroxynonenal (4-HNE), a bioreactive aldehyde, directly correlates with obesity and insulin resistance. The aim of this study was to elucidate the impact of 4-HNE in mediating adipocyte differentiation and function in two metabolically distinct obese groups; the in...

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Vydáno v:	Free radical biology & medicine Ročník 104; s. 129 - 137
Hlavní autoři:	Elrayess, Mohamed A., Almuraikhy, Shamma, Kafienah, Wael, Al-Menhali, Afnan, Al-Khelaifi, Fatima, Bashah, Moataz, Zarkovic, Kamelija, Zarkovic, Neven, Waeg, Georg, Alsayrafi, Mohammed, Jaganjac, Morana
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 01.03.2017
Témata:	4-hydroxynonenal Adipocytes - drug effects Adipocytes - metabolism Adipocytes - pathology Adipogenesis Adipogenesis - drug effects Adult Aldehydes - administration & dosage Aldehydes - metabolism Animals Blood Vessels - drug effects Blood Vessels - metabolism Blood Vessels - pathology Cell Proliferation - drug effects Female Humans Insulin resistance Insulin Resistance - genetics Insulin sensitivity Mice Obesity - drug therapy Obesity - metabolism Obesity - pathology Obesity preadipocytes Oxidative Stress - drug effects Reactive Oxygen Species - metabolism Redox homeostasis Subcutaneous fat SVF ALP IHC ALT SC HDL DBP 4-HNE LDL MHO HMC Adipogenesis RFU SBP SREBF1 AST Insulin sensitivity Obesity preadipocytes DAPI IR IS SOD2 SOD1 4-hydroxynonenal TRX1 DCFH-DA HOMA-IR FABP4 FASN Redox homeostasis ROS Subcutaneous fat PRX2 Insulin resistance FPG PUFAs HE MAP
ISSN:	0891-5849, 1873-4596, 1873-4596
On-line přístup:	Získat plný text
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Shrnutí:	Increased adipose production of 4-hydroxynonenal (4-HNE), a bioreactive aldehyde, directly correlates with obesity and insulin resistance. The aim of this study was to elucidate the impact of 4-HNE in mediating adipocyte differentiation and function in two metabolically distinct obese groups; the insulin sensitive (IS) and the insulin resistant (IR). Subcutaneous (SC) adipose tissues were obtained from eighteen clinically well characterized obese premenopausal women undergoing weight reduction surgery. Cellular distribution of 4-HNE in the form of protein adducts was determined by immunohistochemistry in addition to its effect on oxidative stress, cell growth, adipogenic capacity and insulin signaling in preadipocytes derived from the IS and IR participants. 4-HNE was detected in the SC adipose tissue in different cell types with the highest level detected in adipocytes and blood vessels. Short and long-term in vitro treatment of SC preadipocytes with 4-HNE caused inhibition of their growth and increased production of reactive oxygen species (ROS) and antioxidant enzymes. Repeated 4-HNE treatment led to a greater reduction in the adipogenic capacity of preadipocytes from IS subjects compared to IR and caused dephosphorylation of IRS-1 and p70S6K while activating GSK3α/β and BAD, triggering an IR phenotype. These data suggest that 4-HNE-induced oxidative stress plays a role in the regulation of preadipocyte growth, differentiation and insulin signaling and may therefore contribute to adipose tissue metabolic dysfunction associated with insulin resistance. [Display omitted] •Obesity increases 4-HNE-His adducts in SC adipose tissue adipocytes and blood vessels.•Acute 4-HNE treatment alters redox homeostasis in SC preadipocytes.•Chronic 4-HNE treatment impairs SC adipogenesis and induces insulin resistance.•Chronic 4-HNE treatment has a greater impact on preadipocytes from IS vs IR subjects.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0891-5849 1873-4596 1873-4596
DOI:	10.1016/j.freeradbiomed.2017.01.015