Excess glucocorticoid exposure contributes to adipose tissue fibrosis which involves macrophage interaction with adipose precursor cells

Sarsenbayeva, Assel; Pereira, Maria João; Jui, Bipasha Nandi; Ahmed, Fozia; Dipta, Priya; Fanni, Giovanni; Almby, Kristina E.; Kristófi, Robin; Hetty, Susanne; Eriksson, Jan W.

doi:10.1016/j.bcp.2022.114976

Cited by 7 publications

(6 citation statements)

References 58 publications

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“…In line with this, primary human adipocytes and preadipocytes co-cultured with THP-1 macrophages strongly increased collagen VI expression, most notably through M2-polarized macrophages [ 50 ]. Direct effects on the differentiation of SGBS preadipocytes by macrophages were reported by Sarsenbayeva et al, whereby the presence of macrophages induced αSMA expression in SGBS preadipocytes [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

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The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis

Arndt

Lindhorst

Neugebauer

et al. 2023

IJMS

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White adipose tissue (WAT) fibrosis, characterized by an excess of extracellular (ECM) matrix components, is strongly associated with WAT inflammation and dysfunction due to obesity. Interleukin (IL)-13 and IL-4 were recently identified as critical mediators in the pathogenesis of fibrotic diseases. However, their role in WAT fibrosis is still ill-defined. We therefore established an ex vivo WAT organotypic culture system and demonstrated an upregulation of fibrosis-related genes and an increase of α-smooth muscle actin (αSMA) and fibronectin abundance upon dose-dependent stimulation with IL-13/IL-4. These fibrotic effects were lost in WAT lacking il4ra, which encodes for the underlying receptor controlling this process. Adipose tissue macrophages were found to play a key role in mediating IL-13/IL-4 effects in WAT fibrosis as their depletion through clodronate dramatically decreased the fibrotic phenotype. IL-4-induced WAT fibrosis was partly confirmed in mice injected intraperitoneally with IL-4. Furthermore, gene correlation analyses of human WAT samples revealed a strong positive correlation of fibrosis markers with IL-13/IL-4 receptors, whereas IL13 and IL4 correlations failed to confirm this association. In conclusion, IL-13 and IL-4 can induce WAT fibrosis ex vivo and partly in vivo, but their role in human WAT remains to be further elucidated.

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Section: Discussionmentioning

confidence: 99%

“…Western blotting was performed as recently described [ 51 ]. Total protein from WAT explants was extracted using an extraction buffer (Thermo Fisher Scientific, Waltham, MA, USA) supplemented with a protease and phosphatase inhibitor cocktail (Roche, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis

Arndt

Lindhorst

Neugebauer

et al. 2023

IJMS

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“…GCs like DEX are frequently prescribed for treating different diseases in humans [ 36 ]. However, excess exposure to GC leads to augmented lipid accumulation in the visceral fat depots connected to insulin resistance, obesity, cardiovascular disorders, and different metabolic dysfunctions in either sex [ 31 , 37 ]. Therefore, the current findings might give a deep insight into the multi-dimensional relationship between the DEX dose, duration of DEX treatment, and fat depot weight as well as adipocyte cellularity.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the dynamics and cellularity of adipose tissues in different fat depots in broilers by dietary dexamethasone

Sultana¹,

Islam²

2022

J Adv Vet Anim Res

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Objective: The objective of this investigation was to determine the effects of dexamethasone (DEX) on the weight and cellularity of abdominal and subcutaneous fat depots. Materials and Methods: The study was conducted on four broiler chicks (20 chicks per group) fed commercial feed and water ad libitum. The DEX was supplied with feed at 0 mg/kg (non-DEX), 3 mg/kg (DEX-1), 5 mg/kg (DEX-2), and 7 mg/kg (DEX-3) from day 0 to day 28. The entire abdominal and subcutaneous fat depots were collected and weighed after sacrificing five birds from each group on days 14 and 28. Results: The DEX groups had considerably lower (p < 0.05) fat depot weights with dose-related variation noted among the DEX groups. The histological findings revealed the presence of uniloc¬ular, round to oval-shaped adipocytes. The DEX-1 and DEX-2 had way lower (p < 0.05) numbers of adipocytes while the DEX-3 had considerably higher (p < 0.05) numbers of adipocytes than the non-DEX. DEX-1 and DEX-2 had larger (p < 0.05) adipocytes whereas DEX-3 had smaller adipocytes than the non-DEX. Adipocyte sizes and fat depot weights were found to have very strong negative relationships. Conclusion: Dietary DEX affects the growth and distribution of abdominal and subcutaneous fat depots and adipocyte cellularity subjected to both dose and duration of DEX treatment.

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“…Total RNA was extracted from whole adipose tissue using the RNeasy lipid tissue mini kit (Qiagen). Total RNA extraction from differentiating preadipocytes (d 7 and 14) (n = 4) was performed with the phenol–chloroform extraction method [ 17 , 18 ]. Cells were lysed with Trizol (Sigma), and chloroform (Sigma) was used for phase separation.…”

Section: Methods and Subjectsmentioning

confidence: 99%

“…Differentiated adipocytes, in vitro . Glucose uptake was performed on d 10–14 of differentiation (n = 4) in wild type, negative control and knockdown cultures using the luminescence Glucose Uptake-GLO kit (Promega) according to the manufacturer’s instructions and as previously reported [ 18 ][ 14 ]. In brief, cells were washed 2 times with warmed PBS and then incubated for 2 h in Krebs Ringer HEPES (KRH) buffer containing 0.01% BSA (Sigma), with 5 mM glucose (Sigma), 200 nM adenosine (Sigma), and pH 7.4.…”

Section: Methods and Subjectsmentioning

confidence: 99%

ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation

et al. 2022

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Oestrogen receptor 2 ( ESR2 ) expression has been shown to be higher in subcutaneous adipose tissue (SAT) from postmenopausal compared to premenopausal women. The functional significance of altered ESR2 expression is not fully known. This study investigates the role of ESR2 for adipose tissue lipid and glucose metabolism. SAT biopsies were obtained from 44 female subjects with or without T2D. Gene expression of ESR2 and markers of adipose function and metabolism was assessed. ESR2 knockdown was performed using CRISPR/Cas9 in preadipocytes isolated from SAT of females, and differentiation rate, lipid storage, and glucose uptake were measured. ESR2 expression was inversely correlated with measures of central obesity and expression of some fatty acid oxidation markers, and positively correlated with lipid storage and glucose transport markers. Differentiation was reduced in ESR2 knockdown preadipocytes. This corresponded to reduced expression of markers of differentiation and lipogenesis. Glucose uptake was reduced in knockdown adipocytes. Our results indicate that ESR2 deficiency in women is associated with visceral adiposity and impaired subcutaneous adipocyte differentiation as well as glucose and lipid utilization. High ESR2 expression, as seen after menopause, could be a contributing factor to SAT expansion. This may support a possible target to promote a healthy obesity phenotype.

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Excess glucocorticoid exposure contributes to adipose tissue fibrosis which involves macrophage interaction with adipose precursor cells

Cited by 7 publications

References 58 publications

The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis

The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis

Modulation of the dynamics and cellularity of adipose tissues in different fat depots in broilers by dietary dexamethasone

ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation

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