Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis

Ruiz‐Ojeda, Francisco Javier; Wang, Jiefu; Bäcker, Theresa; Krueger, Martin W.; Zamani, Samira; Rosowski, Simon; Gruber, Tim; Onogi, Yasuhiro; Feuchtinger, Annette; Schulz, Tim J.; Fässler, Reinhard; Müller, Timo; García‐Cáceres, Cristina; Meier, Matthias; Blüher, Matthias; Ussar, Siegfried

doi:10.1016/j.molmet.2020.101147

Cited by 31 publications

(31 citation statements)

References 53 publications

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“…The activity of integrin-β1 is proposed to be impaired during adipogenesis. Adipocyte differentiation is regulated by the downstream signaling of integrin-β1 such as FAK and ERK [ 26 , 27 ]. FSTL1 was proposed as not only an antagonist of BMP4 but also an agonist of TGF-β1 signaling, which plays important roles during lung fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis

Fang

Jia

et al. 2022

Molecular Metabolism

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Objective Although Follistatin-like protein 1 (FSTL1), as an “adipokine”, is highly expressed in preadipocytes, the detail role of FSTL1 in adipogenesis and obesity remains not fully understood. Methods In vitro differentiation of both Fstl1 −/− murine embryonic fibroblasts (MEFs) and stromal vascular fraction (SVF) were measured to assess the specific role of FSTL1 in adipose differentiation. Fstl1 adipocyte-specific knockout mice were generated to evaluate its role in obesity development. Gene expression analysis and phosphorylation patterns were performed to check out the molecular mechanism of the biological function of FSTL1. Results FSTL1 deficiency inhibited preadipocytes differentiation in vitro and obesity development in vivo. Glycosylation at N142 site was pivotal for the biological effect of FSTL1 during adipogenesis; the conversion between PPARγ and p-PPARγ was the key factor for the function of FSTL1. Molecular mechanism studies showed that FSTL1 functions through the integrin/FAK/ERK signaling pathway. Conclusions Our results suggest that FSTL1 promotes adipogenesis by inhibiting the conversion of PPARγ to p-PPARγ through the integrin/FAK/ERK signaling pathway. Glycosylated modification at N142 of FSTL1 is the key site to exert its biological effect.

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Section: Introductionmentioning

confidence: 99%

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis

Fang

Jia

et al. 2022

Molecular Metabolism

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“…Several genes implicated in ECM remodeling in adipose tissue are also involved in SM. Integrins, which play an important function in adipose tissue [8], are implicated in myogenesis [42] and adipogenesis [43]. Thus, integrin striated muscle-specific integrin β1-deficient C57Bl6/J mice exhibit decreased in AKT Ser-473 phosphorylation, glucose uptake, and glycogen synthesis, supporting the role between integrin and insulin signaling in SM [44,45].…”

Section: Current Evidence Of Adipose and Sm Ecm Remodeling In Obesitymentioning

confidence: 87%

“…Integrins play an important role in ECM remodeling in adipose tissue, and they are the main class of tissue receptors implicated in cell-extracellular matrix interactions and cell adhesion. A recent study reveals that integrins, as the main cell surface involved in cell adhesion, interact with insulin receptor in adipocytes modulating WAT insulin sensitivity, demonstrating a new cell-matrix interaction in adipocytes [8]. Therefore, it seems that integrins and insulin signaling interact with each other and play an important role in ECM remodeling in adipose tissue.…”

Section: Current Evidence Of Adipose and Sm Ecm Remodeling In Obesitymentioning

confidence: 99%

“…Regardless of the manner of expansion, variations in ECM composition substantially affect the biomechanical properties of a tissue, as is clearly detected in fibrotic diseases [5]. Fibrosis is characterized by an increase in fibril-forming ECM proteins, and one of the major adhesion receptors implicated in the regulation of this process are integrins, and its signaling in the diet-induced obese state are associated with insulin resistance in adipose tissue [4,[6][7][8]. The inability to develop a healthy adipose tissue expansion under the excess of calories drives an ectopic fat deposition in visceral depots, liver, SM, and other cell types [9].…”

Section: Introductionmentioning

confidence: 99%

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Omics Approaches in Adipose Tissue and Skeletal Muscle Addressing the Role of Extracellular Matrix in Obesity and Metabolic Dysfunction

Anguita‐Ruiz

Bustos-Aibar

Plaza‐Díaz

et al. 2021

IJMS

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Extracellular matrix (ECM) remodeling plays important roles in both white adipose tissue (WAT) and the skeletal muscle (SM) metabolism. Excessive adipocyte hypertrophy causes fibrosis, inflammation, and metabolic dysfunction in adipose tissue, as well as impaired adipogenesis. Similarly, disturbed ECM remodeling in SM has metabolic consequences such as decreased insulin sensitivity. Most of described ECM molecular alterations have been associated with DNA sequence variation, alterations in gene expression patterns, and epigenetic modifications. Among others, the most important epigenetic mechanism by which cells are able to modulate their gene expression is DNA methylation. Epigenome-Wide Association Studies (EWAS) have become a powerful approach to identify DNA methylation variation associated with biological traits in humans. Likewise, Genome-Wide Association Studies (GWAS) and gene expression microarrays have allowed the study of whole-genome genetics and transcriptomics patterns in obesity and metabolic diseases. The aim of this review is to explore the molecular basis of ECM in WAT and SM remodeling in obesity and the consequences of metabolic complications. For that purpose, we reviewed scientific literature including all omics approaches reporting genetic, epigenetic, and transcriptomic (GWAS, EWAS, and RNA-seq or cDNA arrays) ECM-related alterations in WAT and SM as associated with metabolic dysfunction and obesity.

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“…However, β3 expression in fat tissue is related to body fat mass and insulin resistance. Thus, high body fat mass and insulin resistance induce high β3 expression [66]. Noteworthy, insulin-resistant tissues are characterized by a reduced DCI content [2].…”

Section: Integrinsmentioning

confidence: 99%

New Insights into the Activities of D-Chiro-Inositol: A Narrative Review

Gambioli¹,

Oliva

Nordio

et al. 2021

Biomedicines

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D-chiro-inositol (DCI) is a natural compound detectable in cell membranes, which is highly conserved as a biological signaling molecule. In mammals, its function is primarily characterized in the intracellular transduction cascade of insulin. In particular, insulin signal promotes the release of pivotal DCI-containing molecules. In fact, impaired release of DCI is a common feature of insulin-resistant tissues, and insulin-sensitizing pharmaceuticals induce higher concentrations of free DCI. Moreover, it also plays important roles in several other processes. DCI is involved in the regulation of steroidogenesis, due to its regulatory effects on steroidogenic enzymes, including 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, and aromatase. Such regulation of various enzymes indicates a mechanism by which the body regulates different processes via a single molecule, depending on its concentration. DCI also reduces the expression of integrin β3, which is an adhesion molecule involved in embryo implantation and cellular phenomena such as survival, stemness, and invasiveness. In addition, DCI seems to have important anti-inflammatory activities, like its 3-O-methyl-ether, called pinitol. In vitro evidence demonstrates that treatment with both compounds induces a reduction in pro-inflammatory factors—such as Nf-κB—and cytokines—such as TNF-α. DCI then plays important roles in several fundamental processes in physiology. Therefore, research on such molecule is of primary importance.

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Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis

Cited by 31 publications

References 53 publications

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis

Omics Approaches in Adipose Tissue and Skeletal Muscle Addressing the Role of Extracellular Matrix in Obesity and Metabolic Dysfunction

New Insights into the Activities of D-Chiro-Inositol: A Narrative Review

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