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

Elrayess, Mohamed A.; Almuraikhy, Shamma; Kafienah, Wáel; Al-Menhali, Afnan Saleh; Al-Khelaifi, Fatima; Bashah, Moataz; Žarković, Kamelija; Žarković, Neven; Waeg, Georg; Alsayrafi, Mohammed; Jaganjac, Morana

doi:10.1016/j.freeradbiomed.2017.01.015

Cited by 56 publications

(62 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The superior adipogenesis of combined treatment was further confirmed by treating cells from IR individuals with metformin in the presence of insulin. The 4-HNE treatment reduced adipogenesis, also reported previously [6], [13], [21], however this phenotype was rescued in the presence of insulin. Furthermore, 4-HNE and metformin significantly induced intracellular adipocyte ROS production in vitro while this effect was also partially blunted by insulin.…”

Section: Discussionsupporting

confidence: 81%

“…The anti-inflammatory role of insulin [51] in the combined treatment group, manifested by lower circulating IL-6, reduced macrophage infiltration within the adipose tissue and the subsequent lower 4-HNE accumulation and ROS production, may have contributed to improved adipogenesis in these patients although the exact mechanism remains to be investigated. Indeed, the anti-adipogenic roles of IL-6 and 4-HNE in sub-cutaneous tissues from insulin resistance and T2DM were recently suggested [5], [6] and the emerging data may suggest a similar role in OM preadipocytes. Fig.…”

Section: Discussionmentioning

confidence: 98%

“…Immunohistochemical analysis of adipose tissues biopsies was performed as previously described [6]. Briefly, formalin-fixed and paraffin-embedded sections made from paraffin blocks were stained with Haematoxylin/Eosin (HE) or with a monoclonal antibody specific for the HNE-histidine epitope in HNE-protein (peptide) conjugates.…”

Section: Methodsmentioning

confidence: 99%

“…Preadipocytes, an abundant cell population within the adipose tissue, replenish the adipocyte pool through adipogenesis [4]. Superior adipogenesis of preadipocytes isolated from sub-cutaneous (SC) adipose tissues taken from IS obese individuals compared to insulin resistant (IR) counterparts was recently suggested to play a role in the protection process of IS obesity, which is partially mediated by lower IL-6 secretion and oxidative stress [5], [6]. Obesity-associated oxidative stress leads to elevated reactive oxygen species (ROS) production causing lipid peroxidation within the adipose tissue [7] and accumulation of reactive aldehydes [8], [9].…”

Section: Introductionmentioning

confidence: 99%

“…Elevated 4-hydroxynonenal (4-HNE), a bioactive lipid peroxidation product, leads to progressive impairment of cell structure and function via formation of stable 4-hydroxyalkenals with proteins, phospholipids and DNA [10], [11]. Elevation of 4-HNE has been associated with impaired adipogenesis, insulin resistance, atherosclerosis and even obesity of apparently healthy people [6], [12], [13], [14], [15].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

et al. 2017

Self Cite

View full text Add to dashboard Cite

ObjectiveObesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype.MethodsOM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment.ResultsPreadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin.ConclusionThis study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

A small nucleolar RNA, SNORD126, promotes adipogenesis in cells and rats by activating the PI3K–AKT pathway

Mei

Fang

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Small nucleolar RNA (snoRNA) plays important role in various histogenesis. Whether snoRNA plays a role in adipogenesis is unknown. SNORD126 is a C/D box snoRNA. We previously demonstrated that SNORD126 promoted hepatocellular carcinoma cell growth by activating the phosphoinositide 3-kinase-protein kinase B (Akt) pathway through upregulating fibroblast growth factor receptor 2 expression.In the present study, we found that the expression of SNORD126 was downregulated in the obesity-related tissues in high-fat diet-fed rats. Overexpression of SNORD126 in 3T3-L1 cells promoted adipocytes differentiation. SNORD126 significantly increased the expression of CCAAT/enhancer-binding protein α, fatty acid-binding protein 4, peroxisome proliferative-activated receptor-γ, and the phosphorylation of Akt and p70S6K. Overexpression of SNORD126 in human adipose-derived stem cells stimulated adipogenesis and increased phosphorylation of Akt. Meanwhile, SNORD126 increased the messenger RNA and protein levels of cyclin D1 and cyclin-dependent kinase 2, which promoted mitotic clonal expansion progression during the early stage of 3T3-L1 cell differentiation. We further found that SNORD126 accelerated the growth of the groin fat pad and increased phosphorylation of Akt and p70S6K in rats. Overall, our results suggested that SNORD126 promoted adipocyte differentiation through increasing phosphorylation of Akt and p70S6K both in vitro and in vivo.

show abstract

Immunohistochemistry

Khelfi

2024

Biomarkers of Oxidative Stress

View full text Add to dashboard Cite

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

Cited by 56 publications

References 51 publications

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

A small nucleolar RNA, SNORD126, promotes adipogenesis in cells and rats by activating the PI3K–AKT pathway

Immunohistochemistry

Contact Info

Product

Resources

About