Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes

Kahles, Florian; Findeisen, Hannes M.; Bruemmer, Dennis

doi:10.1016/j.molmet.2014.03.004

Cited by 333 publications

(311 citation statements)

References 119 publications

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“…IGFBP3-treated adipocytes exhibit insulin resistance (36), and mice overexpressing Igfbp3 exhibit decreased glucose uptake in AT and muscle (37). Mice lacking Spp1 (osteopontin) are less likely to develop obesity and insulin resistance and exhibit less AT macrophage infiltration (34,35). The ability of OSM to promote the expression of these paracrine and endocrine mediators that favor insulin resistance reveals a possible mechanism whereby OSM perpetuates AT inflammation in obesity (see Fig.…”

Section: Discussionmentioning

confidence: 99%

Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

Elks

Zhao

Grant

et al. 2016

Journal of Biological Chemistry

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Oncostatin M (OSM) is a multifunctional gp130 cytokine.Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor ␤ (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. Adipose tissue (AT) 3 plays an important role in the maintenance of systemic metabolic homeostasis. Adipokine production is a critical AT function and is highly regulated in several physiological and pathological conditions, including AT expansion, insulin resistance, obesity, and type 2 diabetes. Obesity is closely associated with a chronic, low grade inflammatory state characterized by macrophage infiltration of AT and subsequent proinflammatory adipokine expression (1, 2). Adipokine modulation has been shown to be a key contributor to the insulin resistance often observed in obesity.Cytokines in the interleukin-6 (IL-6)/gp130 family include IL-6, IL-11, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, and oncostatin M (OSM) (3). The gp130 cytokines regulate several physiological and biological processes (4), and some of these cytokines, namely IL-6 and ciliary neurotrophic factor, have profound effects on metabolism and as such have been previous targets for obesity treatment (5-8). Although originally identified for its ability to inhibit tumorigenesis (9), OSM modulates a host of other biological processes that are cell type-dependent (10). Elevated OSM levels have been observed in a variety of inflammatory diseases in humans, including rheumatoid arthritis and atherosclerosis (11,12). OSM also has important roles in hepatic insulin resistance and steatosis (13), inflammation (14), and cardiomyocyte remodeling (15) and has several well characterized actions in the liver (16 -18). Unlike other gp130 cytokines, OSM has its own specific receptor subunit (OSM receptor ␤; hereafter referred to as OSMR) that heterodimerizes with gp130 to create the functional OSM receptor complex, and this complex is responsible for the majority of OSM effects (19).Adipocytes and AT are highly responsive to OSM (20), and Osmr is highly expressed in AT compared with other tissues (21, 22). Significant induction of both Osm and Osmr expres-* This work was supported in part by National Institutes of Health Grant R01DK052968 (to J. M. S.) and National Institutes of Health Nutrition Obesity Research Centers Grant P30DK072476 entitled "Nutritional Programming: Environmental and Molecular Interactions." The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Section: Discussionmentioning

confidence: 99%

Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

Elks

Zhao

Grant

et al. 2016

Journal of Biological Chemistry

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“…Adipose tissue and adipocytes are two of the primary sites of OPN synthesis [5,28] . Previous studies have shown that OPN expression is strongly upregulated in adipose tissue from HFD-fed mice [7,9] .…”

Section: Discussionmentioning

confidence: 99%

“…Currently, OPN has been implicated in the pathogenesis of insulin resistance, obesity, and diabetes [5] . The pharmacological and genetic inhibition of OPN has mitigated hepatic and adipose tissue inflammation, improved obesityinduced insulin resistance in hepatic and adipose tissue, attenuated hepatic steatosis, and prevented the upregulation of gluconeogenic genes in the liver [6][7][8][9] , suggesting that OPN is an important player in the development of insulin resistance and diabetes.…”

Section: Introductionmentioning

confidence: 99%

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Zhang

Tang

et al. 2015

Acta Pharmacol Sin

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Aim: Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes. Methods: Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively. Results: Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZinduced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression. Conclusion: Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.

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“…OPN is produced by different cell lines and binds to several integrin receptors and is known to induce cell adhesion, migration, and survival of immune cells including neutrophils, macrophages, T cells, mast cells, and osteoclasts [14].Secreted OPN appears to have a role in the development of psoriasis through inhibiting keratinocyte apoptosis, thereby supporting enhanced epidermal proliferation. OPN promotes vessel formation subsequently supporting the influx of inflammatory cells.OPN has a pro-angiogenic effect on microvascular endothelial cells, and has been involved in the onset of angiogenesis through a mechanism mediated by IL-1 [15].Moreover, there are reports suggest that OPN and MMP-9 may be regulated by TNFα, indicating that they may have a role in the pathogenesis of psoriasis We aimed to assess metabolic syndrome and osteopontin and their associated systemic comorbidities in patients with psoriasis In our study, FBS level was found to benonsignificantlymore in psoriatic cases rather than control.…”

Section: Discussion:-mentioning

confidence: 99%

Metabolic Syndrome and Elevatedosteopontin: Their Associated Comorbidities in Patients With Psoriasis.

Bakr.¹,

MDS.²,

MD.³

et al. 2017

IJAR

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Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes

Cited by 333 publications

References 119 publications

Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Metabolic Syndrome and Elevatedosteopontin: Their Associated Comorbidities in Patients With Psoriasis.

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