Oncostatin M Is Produced in Adipose Tissue and Is Regulated in Conditions of Obesity and Type 2 Diabetes

Sánchez‐Infantes, David; White, Ursula; Elks, Carrie M.; Morrison, Ron F.; Gimble, Jeffrey M.; Considine, Robert V.; Ferrante, Anthony W.; Ravussin, Éric; Stephens, Jacqueline M.

doi:10.1210/jc.2013-3555

Cited by 66 publications

(90 citation statements)

References 52 publications

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“…OSM is not produced by adipocytes but is made in cells comprising the stromal vascular fraction (SVF) of human AT (22). We have shown that OSM is expressed in AT macrophages (22) in mice, and others have shown that OSM is produced in liver Kupffer cells where it contributes to steatosis and insulin resistance (13). The majority of studies support a role for OSM in promoting metabolic dysfunction.…”

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confidence: 96%

“…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 sion occurs in AT of obese mice and humans (22).…”

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confidence: 99%

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confidence: 99%

“…Significant induction of both Osm and Osmr expres-* This work was supported in part by National Institutes of Health Grant sion occurs in AT of obese mice and humans (22). OSM is not produced by adipocytes but is made in cells comprising the stromal vascular fraction (SVF) of human AT (22). We have shown that OSM is expressed in AT macrophages (22) in mice, and others have shown that OSM is produced in liver Kupffer cells where it contributes to steatosis and insulin resistance (13).…”

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confidence: 99%

“…For example, it is well documented that OSM inhibits adipogenesis (23,24). In addition, OSM induces plasminogen activator inhibitor-1 (PAI-1) expression in murine adipocytes (22) and in human AT (25). PAI-1 is a known player in metabolic dysfunction (26,27).…”

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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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confidence: 96%

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confidence: 99%

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confidence: 99%

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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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The Use of Silk as a Scaffold for Mature, Sustainable Unilocular Adipose 3D Tissue Engineered Systems

Abbott

Wang

Reagan³

et al. 2016

Adv Healthcare Materials

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There is a critical need for monitoring physiologically relevant, sustainable, human adipose tissues in vitro to gain new insights into metabolic diseases. To support long term culture, a 3D silk scaffold assisted culture system was developed that maintained mature unilocular adipocytes ex vivo in co-culture with pre-adipocytes, endothelial cells, and smooth muscle cells obtained from small volumes of liquefied adipose samples. Without the silk scaffold, adipose tissue explants could not be sustained in long term culture (3 months) due to their fragility. Adjustments to media components were used to tune lipid metabolism and proliferation, in addition to responsiveness to an inflammatory stimulus. Interestingly, patient specific responses to TNFα stimulation were observed, providing a proof of concept translational technique for patient specific disease modeling in the future. In summary, our novel 3D scaffold assisted approach is required for establishing physiologically relevant, sustainable, human adipose tissue systems from small volumes of lipoaspirate, making this methodology of great value to studies of metabolism, adipokine-driven diseases, and other diseases where the roles of adipocytes are only now becoming uncovered.

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Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation

Kaji

2016

Comprehensive Physiology

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Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner. Adipocyte-derived PAI-1, predominantly expressed in visceral fat, is released into the circulation in parallel with increased fat mass, and it functions as a crucial adipokine that negatively affects physiological metabolism and vascular biology. Elevated PAI-1 levels induce insulin resistance and metabolic abnormalities during proinflammatory processes involving several cytokines and chemokines in diabetes. Several studies have indicated that PAI-1 plays crucial roles in insulin actions on liver, muscle, and fat. Accumulated fat and enhanced adipose tissue-derived PAI-1 influence metabolism and vessels in relation to macrophage infiltration, chronic inflammation, and free fatty acid release in obese states. PAI-1-induced fibrinolysis abnormalities are associated with metabolic syndrome, leading to cardiovascular disease through dysregulated vascular coagulation, endothelial dysfunction, and metabolic abnormalities. Adipose tissue-derived PAI-1 is involved in insulin resistance, osteoporosis, and sarcopenia induced by glucocorticoid excess in mice. Moreover, PAI-1 is involved in the other pathological states, such as nonalcoholic fatty liver disease, and cancer. As such, PAI-1 may be exploited as a marker of disease activity as well being a target for clinical drug development. © 2016 American Physiological Society. Compr Physiol 6:1873-1896, 2016.

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Oncostatin M Is Produced in Adipose Tissue and Is Regulated in Conditions of Obesity and Type 2 Diabetes

Cited by 66 publications

References 52 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

The Use of Silk as a Scaffold for Mature, Sustainable Unilocular Adipose 3D Tissue Engineered Systems

Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation

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