Uncovering the Role of p38 Family Members in Adipose Tissue Physiology

Leiva, Magdalena; Matesanz, Nuria; Pulgarín-Alfaro, Marta; Nikolić, Ivana; Sabio, Guadalupe

doi:10.3389/fendo.2020.572089

Cited by 35 publications

(22 citation statements)

References 204 publications

(311 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a massive phosphorylation of p65 was observed, suggesting an additional effect of VDD and HF diet in male, as observed for inflammatory pathways and adiposity index. A significant induction of p38 phosphorylation was observed in the CTRL HF group, which is coherent since this pathway is known to be inducted during obesity [39]. Nevertheless, no impact of VDD was observed on the pathway.…”

Section: Discussionsupporting

confidence: 74%

“…Concerning molecular mechanisms, RNA seq and miRNA analysis as well as bibliography strongly converge to the putative role of NF-kB and p38/MAPK signaling pathways. Indeed, NF-kB and p38 are known to play a major role during adipose tissue inflammation [38,39]. Furthermore, we and others have demonstrated that the ability of VD to blunt inflammation in adipocytes and adipose tissue was linked to an inhibition of phosphorylation of these two signaling pathways [21,26,[40][41][42].…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

Maternal Vitamin D Deficiency in Mice Increases White Adipose Tissue Inflammation in Offspring

Haroun

Bennour

Seipelt

et al. 2022

Cells

View full text Add to dashboard Cite

Vitamin D is acknowledged to play an important biological and metabolic role in adipose tissue, which is also the main storage site for this vitamin. Its anti-inflammatory effect in adipocytes and adipose tissue has notably been highlighted in adult mice. This vitamin is also crucial during fetal development since maternal vitamin D deficiency is suspected to program future metabolic disorders. Based on these observations, the aim of this study was to evaluate the consequences of maternal vitamin D deficiency (VDD) on white adipose tissue inflammation in adult offspring fed with normal or obesogenic diet (high-fat diet). White adipose tissue morphology, RNA and miRNA expression profiles, and signaling pathways were studied in adult males and females. In males, a HF diet coupled with maternal VDD increased expression of RNA and miRNA linked to inflammation leading to over-representation of inflammatory pathways. Interestingly, genomic and epigenetic profiles were associated with activation of the NF-kB signaling pathway and adiposity index. In females, no major modulation of inflammatory pathways was observed under VDD, contrarily to males. We concluded that maternal VDD coupled with HF diet activated inflammatory pathway in adipose tissue of the offspring, in a sex-dependent manner. Such activation is strongly related to activation of NF-kB signaling and increased adiposity only in males.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 84%

Maternal Vitamin D Deficiency in Mice Increases White Adipose Tissue Inflammation in Offspring

Haroun

Bennour

Seipelt

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…p38 can exert protective or deleterious roles in different cell types, which are highly dependent on the type of stimulus. Activation of p38 elicits protective effects during ischemic conditions ( Nakano et al, 2000 ; Fujimoto et al, 2004 ; Hsu et al, 2007 ) and plays an important role in the activation of brown adipose tissue ( Leiva et al, 2020 ). However, activation of p38 has been linked to inflammatory cytokine production ( Li et al, 2005 ) and ASC aging ( Zhang et al, 2020 ), and its inhibition potentiates ASC and EV therapy ( Zhang et al, 2017 ; Chen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity

Eirin

Meng

Zhu

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Obesity is a chronic disease that interferes with normal repair processes, including adipose mesenchymal stem/stromal cells (ASCs) function. ASCs produce extracellular vesicles (EVs) that activate a repair program in recipient cells partly via their micro-RNA (miRNA) cargo. We hypothesized that obesity alters the miRNA expression profile of human ASC-derived EVs, limiting their capacity to repair injured cells. Human ASCs were harvested from obese and age- and gender-matched non-obese (lean) subjects during bariatric or cosmetic surgeries, respectively (n = 5 each), and their EVs isolated. Following high-throughput sequencing analysis, differentially expressed miRNAs were identified and their gene targets classified based on cellular component, molecular function, and biological process. The capacity of human lean- and obese-EVs to modulate inflammation, apoptosis, as well as mitogen-activated protein kinase (MAPK) and Wnt signaling in injured human proximal tubular epithelial (HK2) cells was evaluated in vitro. The number of EVs released from lean- and obese-ASCs was similar, but obese-EVs were smaller compared to lean-EVs. Differential expression analysis revealed 8 miRNAs upregulated (fold change > 1.4, p < 0.05) and 75 downregulated (fold change < 0.7, p < 0.05) in obese-EVs vs. lean-EVs. miRNAs upregulated in obese-EVs participate in regulation of NFk-B and MAPK signaling, cytoskeleton organization, and apoptosis, whereas those downregulated in obese-EVs are implicated in cell cycle, angiogenesis, and Wnt and MAPK signaling. Treatment of injured HK2 cells with obese-EVs failed to decrease inflammation, and they decreased apoptosis and MAPK signaling significantly less effectively than their lean counterparts. Obesity alters the size and miRNA cargo of human ASC-derived EVs, as well as their ability to modulate important injury pathways in recipient cells. These observations may guide development of novel strategies to improve healing and repair in obese individuals.

show abstract

“…Additionally, the combination of hispidulin and p -synephrine resulted in a decreased protein expression of the transcription factor C/EBPβ, which plays a principal role in orchestrating early steps of adipogenesis [ 71 ]. During the early stage of adipogenesis, the nuclear localization of C/EBPβ is mediated by the activation of ERK, P38, and GR in response to adipogenic stimuli [ 72 , 73 , 74 ]. In addition, glucocorticoid hormones affect adipocyte differentiation and the maintenance of adipogenic genes by binding to GR, a ligand-activated transcription factor [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes

et al. 2021

View full text Add to dashboard Cite

Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein β. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs.

show abstract

Uncovering the Role of p38 Family Members in Adipose Tissue Physiology

Cited by 35 publications

References 204 publications

Maternal Vitamin D Deficiency in Mice Increases White Adipose Tissue Inflammation in Offspring

Maternal Vitamin D Deficiency in Mice Increases White Adipose Tissue Inflammation in Offspring

The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity

Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes

Contact Info

Product

Resources

About