Barb D, Williams CJ, Neuwirth AK, Mantzoros CSAdiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr 86(3): s858-s866

Division of Endocrinology, Diabetes and Metabolism and Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 10/2007; 86(3):s858-66.
Source: PubMed


Adiponectin, an adipocyte-secreted hormone that plays an important role in diabetes and cardiovascular disease, may also be of importance in the development and progression of several malignancies. Circulating adiponectin concentrations, which are determined mainly by genetic factors, nutrition, and adiposity, are lower in patients with breast, endometrial, prostate, and colon cancer. It has thus been proposed that adiponectin may be a biological link between obesity (especially central obesity) and increased cancer risk. Adiponectin may influence cancer risk through its well-recognized effects on insulin resistance, but it is also plausible that adiponectin acts on tumor cells directly. Several cancer cell types express adiponectin receptors that may mediate the effects of adiponectin on cellular proliferation. Herein, we review recent evidence supporting a role of serum adiponectin concentrations as a novel risk factor and possible diagnostic marker for obesity-related malignancies, including cancers of the breast, endometrium, colon, and prostate. Further studies are needed to fully elucidate the potential role of adiponectin in cancer diagnostics and therapeutics.

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    • "Among the various adipokines, adiponectin is the most abundant in the plasma (Swarbrick and Havel, 2008) and possesses diverse biological functions. In addition to its well-known functions of lipid metabolism, insulin sensitization (Yamauchi et al., 2002) and anti-inflammation (Ouchi and Walsh, 2007), a growing body of evidence highlights adiponectin possesses potent anti-tumor activities (Barb et al., 2007) through various mechanisms, including inhibition of metastasis, angiogenesis and proliferation of cancer cells (Brakenhielm et al., 2004). In particular, recent studies have shown that adiponectin suppresses growth of cancer cells through different mechanisms(Kelesidis et al., 2006). "
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    ABSTRACT: Adiponectin predominantly secreted from adipose tissue has exhibited potent anti-proliferative properties in cancer cells via modulating cell cycle and apoptosis. FoxO3A, a Forkhead box O member of the transcription factor, plays a critical role in modulating expression of genes involved in cell death and/or survival. In this study, we investigated the role of FoxO3A signaling in anti-cancer activities of adiponectin. Herein, we have shown that treatment with globular adiponectin (gAcrp) increases p27 but decreases cyclinD1 expression in human hepatoma (HepG2) and breast (MCF-7) cancer cells. Gene ablation of FoxO3A prevented gAcrp-induced increase in p27 and decreased in cyclin D1 expression, and further ameliorated cell cycle arrest by gAcrp, indicating a critical role of FoxO3A in gAcrp-induced cell cycle arrest of cancer cells. Moreover, treatment with gAcrp also induced caspase-3/7 activation and increased Fas ligand (FasL) expression in both HepG2 and MCF-7 cells. Transfection with FoxO3A siRNA inhibited gAcrp-induced caspase-3/7 activation and FasL expression, suggesting that FoxO3A signaling also plays an important role in gAcrp-induced apoptosis of cancer cells. We also found that gene silencing of AMPK prevented gAcrp-induced nuclear translocation of FoxO3A in HepG2 and MCF-7 cells. In addition, suppression of AMPK also blocked gAcrp-induced cell cycle arrest and further attenuated gAcrp-induced caspase-3/7 activation, indicating that AMPK signaling plays a pivotal role in both gAcrp-induced cell cycle arrest and apoptosis via acting as an upstream signaling of FoxO3A. Taken together, our findings demonstrated that AMPK/FoxO3A axis plays a cardinal role in anti-proliferative effect of adiponectin in cancer cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cellular Physiology 06/2015; 231(2). DOI:10.1002/jcp.25080 · 3.84 Impact Factor
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    • "Adiponectin, regulates carbohydrate and lipid metabolism, insulin sensitivity and regulates growth pathways [20, 68]. Decreased adiponectin levels have been reported under high energy conditions and in various malignancies [20, 21, 69]. While leptin was increased in HED mice, we did not see any change in adiponectin levels (Figs. "
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    ABSTRACT: A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.
    Oncotarget 07/2014; 5(15). DOI:10.18632/oncotarget.2168 · 6.36 Impact Factor
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    • "This interaction is essential to verify its biological activity. Adiponectin is expressed as a single subunit but circulates in plasma or serum in four isoform states [21] (Fig. 1): a simple trimer complex (90 kDa), a low molecular-weight (LMW; 180 kDa), complex of two trimers, a high molecular-weight (HMW; 360– 400 kDa), complex of up to six trimers and a globular form of adiponectin that also exists in plasma [15]. These forms of adiponectin may show divergent biological roles during the activation of downstream signaling pathways, which may define their eventual roles in tumor progression. "
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    ABSTRACT: Adiponectin is produced in the white adipose tissue and is known to have anti-metabolic and anti-inflammatory properties. Serum/plasma adiponectin levels depend on diet, physical activity, and inheritance. Epidemiologic observations suggest a potential link between obesity and gastrointestinal malignancies. Low levels of adiponectin, which are known to occur in obesity, may contribute to the high incidence of cancer in this population. This review discusses the biochemical and molecular evidence regarding the relationship between adiponectin and gastrointestinal carcinogenesis and provides several future perspectives on the role of adiponectin as a target for prevention and therapy.
    Cytokine & Growth Factor Reviews 06/2014; 26(1). DOI:10.1016/j.cytogfr.2014.06.007 · 5.36 Impact Factor
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