Coordinated Regulation of Nutrient and Inflammatory Responses by STAMP2 Is Essential for Metabolic Homeostasis

Wellen, Kathryn E.; Fucho, Raquel; Gregor, Margaret F.; Furuhashi, Masato; Morgan, Carlos; Lindstad, Torstein; Vaillancourt, Eric; Görgün, Cem Z.; Saatcioglu, Fahri; Hotamışlıgil, Gökhan S.

doi:10.1016/j.cell.2007.02.049

Cited by 191 publications

(244 citation statements)

References 194 publications

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“…Besides the positive association with GLUT4, AR mRNA also correlated with RHOA, ROCK2, and VIM, all proteins implicated in the cytoskeleton remodeling required for the insulinstimulated intracellular trafficking of GLUT4 vesicles (Hirata et al 2011, Chun et al 2012. Moreover, a highly significant positive correlation was found between AR and STAMP2, whose expression is required for normal insulin signaling, as demonstrated in loss-of-function studies (Wellen et al 2007). This protein is upregulated by TNF-a and by nutrient stimuli and has been characterized as a counter-regulator of inflammation and insulin resistance in mice (Waki & Tontonoz 2007, Wellen et al 2007.…”

Section: Discussionmentioning

confidence: 70%

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Maneschi¹,

Morelli²,

Filippi³

et al. 2012

Journal of Endocrinology

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We recently demonstrated that testosterone dosing ameliorated the metabolic profile and reduced visceral adipose tissue (VAT) in a high-fat diet (HFD)-induced rabbit model of metabolic syndrome (MetS). We studied the effects of HFD and in vivo testosterone dosing on VAT function and the adipogenic capacity of rabbit preadipocytes isolated from VAT of regular diet (RD), HFD, and testosterone-treated HFD rabbits. VAT was studied by immunohistochemistry, western blot, and RT-PCR. Isolated rPADs were exposed to adipocyte differentiating mixture (DIM) to evaluate adipogenic potential. Adipocyte size was significantly increased in HFD VAT compared with RD, indicating adipocyte dysfunction, which was normalized by testosterone dosing. Accordingly, perilipin, an anti-lipolytic protein, was significantly increased in HFD VAT, when compared with other groups. HFD VAT was hypoxic, while testosterone dosing normalized VAT oxygenation. In VAT, androgen receptor expression was positively associated with mRNA expression of GLUT4 (SLC2A4) (insulin-regulated glucose transporter) and STAMP2 (STEAP4) (androgen-dependent gene required for insulin signaling). In testosterone-treated HFD VAT, STAMP2 mRNA was significantly increased when compared with the other groups. Moreover, GLUT4 membrane translocation was significantly reduced in HFD VAT, compared with RD, and increased by testosterone. In DIM-exposed preadipocytes from HFD, triglyceride accumulation, adipocyte-specific genes, insulin-stimulated triglyceride synthesis, glucose uptake, and GLUT4 membrane translocation were reduced compared with preadipocytes from RD and normalized by in vivo testosterone dosing. In conclusion, testosterone dosing in a MetS animal model positively affects VAT functions. This could reflect the ability of testosterone in restoring insulin sensitivity in VAT, thus counteracting metabolic alterations.

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Section: Discussionmentioning

confidence: 70%

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Maneschi¹,

Morelli²,

Filippi³

et al. 2012

Journal of Endocrinology

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“…However, the regulatory mechanisms and the roles of the anti-inflammatory molecules following changes of energy balance in the adipose tissue are poorly understood. Nonetheless, it has recently been shown that the knock-out of stamp2, an adipocyte-specific anti-inflammatory molecule induced by proinflammatory signals, elevates inflammatory gene expression and macrophage infiltration in the adipose tissue and also triggers metabolic diseases (36), suggesting that innate antiinflammatory or pro-resolving activity of adipose tissue would be critical for maintaining energy homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…Insulted tissues generate not only proinflammatory cytokines but also anti-inflammatory molecules to resolve local and systemic inflammation (34). Accordingly, inflamed adipose tissue in obese animal models exhibits increased expression of several anti-inflammatory molecules such as IL-10, IL-1Ra, and stamp2 as well as proinflammatory cytokines to counterbalance the proinflammatory events (35,36). However, the regulatory mechanisms and the roles of the anti-inflammatory molecules following changes of energy balance in the adipose tissue are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Adipocytokine Orosomucoid Integrates Inflammatory and Metabolic Signals to Preserve Energy Homeostasis by Resolving Immoderate Inflammation

Lee

Choi

Hwang

et al. 2010

Journal of Biological Chemistry

109

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Orosomucoid (ORM), also called ␣-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose Orm levels were elevated by metabolic signals, including insulin, high glucose, and free fatty acid, as well as by the proinflammatory cytokine tumor necrosis factor-␣, which is found in increased levels in the adipose tissue of morbid obese subjects. In both adipocytes and macrophages, ORM suppressed proinflammatory gene expression and pathways such as NF-B and mitogen-activated protein kinase signalings and reactive oxygen species generation. Concomitantly, ORM relieved hyperglycemia-induced insulin resistance as well as tumor necrosis factor-␣-mediated lipolysis in adipocytes. Accordingly, ORM improved glucose and insulin tolerance in obese and diabetic db/db mice. Taken together, our results suggest that ORM integrates inflammatory and metabolic signals to modulate immune responses to protect adipose tissue from excessive inflammation and thereby from metabolic dysfunction.

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“…(25) Interestingly, STAMP2 was recently found to be a critical modulator of the integrated response system of inflammation and metabolism in adipocytes where the targeted deletion of STAMP2 in mice resulted in metabolic syndrome on regular diet. (30) The connection between metabolic syndrome and cancer is an area of great interest. Although the role of metabolic syndrome in prostate cancer is still under debate, the studies of factors that may be involved in both diseases are of significant importance.…”

Section: Stamp Familymentioning

confidence: 99%

Androgen signaling and its interactions with other signaling pathways in prostate cancer

2007

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SummaryProstate cancer is the most frequently diagnosed nonskin cancer and the third leading cause of cancer mortality in men. In the initial stages, prostate cancer is dependent on androgens for growth, which is the basis for androgen ablation therapy. However, in most cases, prostate cancer progresses to a hormone refractory phenotype for which there is no effective therapy available at present. The androgen receptor (AR) is required for prostate cancer growth in all stages, including the relapsed, ''androgen-independent'' tumors in the presence of very low levels of androgens. This review focuses on AR function and AR-target genes and summarizes the major signaling pathways implicated in prostate cancer progression, their crosstalk with each other and with AR signaling. This complex network of interactions is providing a deeper insight into prostate carcinogenesis and may form the basis for novel diagnostic and therapeutic strategies. IntroductionProstate adenocarcinoma is the most frequently diagnosed non-cutaneous male malignancy and the third leading cause of cancer-related death in men in most western industrialized countries. (1) It is estimated that around 660,000 men worldwide will be diagnosed with prostate cancer and 250,000 men will die from it in 2010; thus, it will remain a major health problem in the future. (1) It was more than 60 years ago that the important role of male sex hormones (androgens) for the development and growth of prostate cancer was demonstrated. (2) Accordingly, androgen ablation therapy has been the main line of therapy for prostate cancer. Therefore, much of the focus in prostate cancer research to date has naturally been on androgens, how to decrease the androgens in the circulation and how to inhibit the androgen receptor (AR).In addition to AR signaling, it has now become evident that other signaling pathways, as well as non-genomic and genomic alterations, are involved in prostate cancer development and progression. Furthermore, recent studies indicated that signaling through AR has a critical role even after androgen ablation and disease progression (for review see Ref.3). In the following sections, we give an overview of androgen signaling in prostate cancer, with a special focus on recent findings about AR function and AR target genes. We then review the involvement of other central signaling pathways in prostate cancer, with a special focus on their cross-talk with the AR signaling pathway. Clinical implications of these findings and potential directions for future research are also outlined.

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Coordinated Regulation of Nutrient and Inflammatory Responses by STAMP2 Is Essential for Metabolic Homeostasis

Cited by 191 publications

References 194 publications

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Adipocytokine Orosomucoid Integrates Inflammatory and Metabolic Signals to Preserve Energy Homeostasis by Resolving Immoderate Inflammation

Androgen signaling and its interactions with other signaling pathways in prostate cancer

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