研究生: |
周美佳 Chou, Mei-Jia |
---|---|
論文名稱: |
探討種子胜肽Lunasin對於肥胖引起的發炎模式之免疫調節作用 The effect of seed peptide lunasin on immune regulation in obesity-induced inflammatory models |
指導教授: |
謝佳倩
Hsieh, Chia-Chien |
學位類別: |
碩士 Master |
系所名稱: |
人類發展與家庭學系 Department of Human Development and Family Studies |
論文出版年: | 2016 |
畢業學年度: | 104 |
語文別: | 中文 |
論文頁數: | 123 |
中文關鍵詞: | Lunasin 、肥胖 、發炎 、巨噬細胞 、細胞激素 |
英文關鍵詞: | Cytokine, Inflammation, Lunasin, Macrophage, Obesity |
DOI URL: | https://doi.org/10.6345/NTNU202204040 |
論文種類: | 學術論文 |
相關次數: | 點閱:257 下載:5 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
肥胖伴隨著脂肪組織中數種免疫細胞的浸潤及促發炎細胞激素生成,形成低度慢性發炎環境,與許多慢性疾病的發生相關,更是癌症發生的危險因子之ㄧ。Lunasin為一天然種子胜肽已被證實具有抗腫瘤、抗發炎、抗氧化、降低膽固醇及免疫調節等功用,但對於肥胖相關的發炎反應與其可能的作用機制仍不甚清楚。因此,本研究欲探討lunasin是否具有降低肥胖相關的發炎介質生成,並調節其免疫作用。實驗分為兩部分,實驗主題I:探討lunasin對肥胖相關發炎之免疫細胞的調節。此部分建立三個體外肥胖模式,模式一,以瘦體素 (leptin)刺激RAW264.7細胞之發炎模式;模式二,使用脂肪細胞條件培養液(Adipocyte-conditioned medium, Ad-CM)培養RAW264.7細胞;模式三,RAW264.7巨噬細胞與3T3成熟脂肪細胞共同培養環境,分別同時處理Lunasin。結果發現在LPS+leptin以及LPS+Ad-CM組別,lunasin處理分別顯著抑制促發炎細胞激素IL-6、TNF-α及IL-1生成。在動物實驗部分,為探討lunasin對肥胖小鼠免疫細胞分泌的發炎介質之影響,使用C57BL/6J Narl母鼠,分別餵食低脂 (LF)及高脂 (HF)飲食,收集初代免疫細胞同時加入lunasin處理,發現在LPS刺激之HF組腹腔巨噬細胞,lunasin顯著降低IL-6分泌;而脾臟細胞以PHA刺激培養並加入lunasin的處理,其HF組中的IL-4分泌,顯著降低。進一步探討使用lunasin 低劑量 (HF-LL)與高劑量 (HF-LH) 腹腔注射,對於肥胖小鼠免疫細胞的發炎介質的影響。實驗主題II:探討飲食誘導的肥胖對小鼠乳癌生成之影響。給予飲食誘發肥胖小鼠化學致癌劑DMBA (7,12-Dimethylbenz[a]anthracene)以誘發乳腺癌生成,結果發現在高脂飲食組,給予DMBA腫瘤發生率為20% (n=1/5)及而低脂組為14.3% (n=1/7)。由以上結果可知,在體內與體外實驗中,lunasin處理具有降低肥胖相關的促發炎細胞激素的生成。
Obese progression accompanies chronic inflammation mainly due to infiltrate multiple immune cells in adipose tissue and then produce pro-inflammatory cytokines. This low-grade chronic inflammatorymicro-environment is associated with many chronic diseases, such as type II diabetes mellitus and cancer. Lunasin, is a natural seed peptide, has been shown many bioactivities such as anti-tumoranti-inflammatory, antioxidant, reduce cholesterol, and immune regulation properties. However, there is still a little information described the mechanisms of lunasin acts on obesity-related inflammation, even obesity-related tumor development. Therefore, the present study is to investigate whether lunasin reduced obesity-related inflammatory mediator, and affect immune function. There are two parts of experiments. In the Experiment Ι, to investigate the effects of lunasin on RAW264.7 macrophages in obese physiological model, the RAW264.7 cells were cultured in mediacontaining leptin, adipocye conditioned medium (Ad -CM), or co-culture of adipocyte and macrophage in transwell system, and then treated with lunasin plus LPS stimulation, respectively. The results were showed that the secretions of MCP-1 and IL-1β were decreased by lunasin treatment in leptin and Ad-CM conditions plus LPS stimulation at the same time. Subsequently, in vivo studies were carried on to investigate the effect of lunasin regulate immune cells ofmice fed the experimental diets. The C57BL/ 6J Narl female mice fed the experiment diets containing low-fat (LF) and high-fat (HF) for 10 weeks. The results were showed that the secretion of IL-6 in peritoneal cells stimulated by LPS of HF group was decreased by lunasin treatment. To confirm the effect of lunasin, intraperitoneal injection (IP) of lunasin, at 20 mg/kg and 4 mg/kg body weight was used in dietary induced obese mice (HF) and control mice (LF). In Experiment II, to investigate the effects of breast tumorigenesis in obese mice, a model of oral gavage chemical carcinogen 7,12-Dimethylbenz [a] anthracene (DMBA) induced breast cancer in C57BL/ 6J Narl female mice fed the experiment diet LF and HF for 10 weeks was built. The mice were divided into a LF, HF, LF+DMBA (LFD) and HF+DMBA (HFD), weekly monitoring tumorigenesis situation. The results indicated that incidence of breast tumors is about 20% in HFD group and 14.3% in LFD group.
In summary, the results indicated that lunasin reduced proinflammatory cytokine productions in both in vitro and in vivo models, suggesting lunasin executes potentially anti-inflammatory actions in the obesity-related conditions. More studies are needed to explore the mechanisms of lunasin’s action in the obesity related inflammation and tumorigenesis.
黃渝珊. (2015) 探討Lunasin及Aspirin的處理對脂肪細胞與乳癌細胞其發炎及生長之影響. 國立臺灣師範大學人類發展與家庭學系暨研究所碩士論文
Abbas, A. K., Murphy, K. M, & Sher A. (1996). Functional diversity of helper T lymphocytes. Nature, 383(6603), 787-93.
Acedo, S. C., Gambero, S., Cunha, F. G., Lorand-Metze, I., & Gambero, A. (2013). Participation of leptin in the determination of the macrophage phenotype: an additional role in adipocyte and macrophage crosstalk. In Vitro Cellular & Developmental Biology - Animal, 49(6), 473-8.
Ahn, J., Lee, H., Kim, S., & Ha, T. (2007). Resveratrol inhibits TNF-alpha-induced changes of adipokines in 3T3-L1 adipocytes. Biochemical and Biophysical Research Communications, 364(4), 972-7.
Ajuwon, K. M, & Spurlock, M. E. (2005). Palmitate activates the NF-kappaB transcription factor and induces IL-6 and TNF alpha expression in 3T3-L1 adipocytes. Journal of Nutrition, 135(8), 1841-6.
Akira, S., & Takeda, K (2004). Toll-like receptor signalling. Nature Reviews Immunology, 4(7), 499-511.
Allan, S. M, Tyrrell, P. J., & Rothwell, N. J. (2005). Interleukin-1 and neuronal injury. Nature Reviews Immunology, 5(8), 629-40.
Barton, G.M., & Medzhitov, R. (2002). Control of adaptive immune responses by Toll-like receptors. Current Opinion in Immunology, 14(3), 380-3.
Calder, P.C., Ahluwalia, N., Albers, R., Bosco, N., Bourdet-Sicard R. et al (2013). A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. British Journal of Nutrition, 109 Suppl 1, S1-34.
Chidambaram, N., & Baradarajan, A. (1996). Influence of selenium on glutathione and some associated enzymes in rats with mammary tumor induced by 7, 12- dimethylbenz(a)anthracene. Molecular and Cellular Biochemistry, 156(2), 101-7.
Cho, S. Y., Park, S. J., Kwon, M. J., Jeong, T. S., Bok, S. H., Choi, W. Y. et al. (2003). Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-κB pathway in lipopolysaccharide-stimulated macrophage. Molecular and Cellular Biochemistry, 243(1-2), 153-60.
Chusyd, D. E., Wang, D., Huffman, D. M., & Nagy, T. R. (2016). Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots. Frontiers in Nutrition, 3, 10.
Cleary, M. P., Grossmann, M. E., & Ray, A. (2010). Effect of obesity on breast cancer development. Veterinary Pathology, 47(2), 202-13.
Collins, S., Martin, T. L., Surwit, R. S., & Robidoux, J. (2004). Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiology & Behavior, 81(2), 243-8.
Cowen, S., McLaughlin, S. L., Hobbs, G., Coad, J., Martin, K. H., Olfert, I. M., et al. (2015). High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer. Cancers (Basel), 7(3), 1125-42.
Cullberg, K. B., Larsen, J., Pedersen, S. B., & Richelsen, B. (2014). Effects of LPS and dietary free fatty acids on MCP-1 in 3T3-L1 adipocytes and macrophages in vitro. Nutrition & Diabetes, 4, e113.
De Boer, A. A., Monk, J. M., & Robinson, L. E. (2014). Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model. PLoS One, 9(1), e85037.
de Mejia, E. G. & Dia, V. P. (2009). Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-kappaB pathway in the macrophage. Peptides, 30(12), 2388-98.
de Mejia, E. G., Vasconez, M., deLumen B. O., & Nelson R. (2004). Lunasin concentration in different soybean genotypes, commercial soy protein, and isoflavone products. Journal of Agricultural and Food Chemistry, 52, 5882-7.
Dia, V. P., & Mejia, E. G. (2010). Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Letters, 295(1), 44-53.
Dia, V. P., Torres, S., De Lumen, B. O., Erdman, J. W., Jr, & De Mejia, E. G. (2009). Presence of lunasin in plasma of men after soy protein consumption. Journal of Agricultural and Food Chemistry, 57(4), 1260-6.
Dia, V.P. & de Mejia, E.G. (2013). Potential of Lunasin Orally-Administered in Comparison to Intraperitoneal Injection to Inhibit Colon Cancer Metastasis in Vivo. Journal of Cancer Therapy, (4), 34-43.
Dias, M., Cabrita, S., Sousa, E., França, B., Patrício, J., & Oliveira, C. (1999). Benign and malignant mammary tumors induced by DMBA in female Wistar rats. European Journal of Gynaecological Oncology, 20(4), 285-8.
Donepudi, M. S., Kondapalli, K., Amos, S. J, & Venkanteshan, P. (2014). Breast cancer statistics and markers. Journal of Cancer Research and Therapeutics, 10(3), 506-11.
Dubois, V., Delort, L., Billard, H., Vasson, M. P., & Caldefie-Chezet, F. (2013). Breast cancer and obesity: in vitro interferences between adipokines and proangiogenic features and/or antitumor therapies? PLOS One, 8(3), e58541.
Dzirkale, Z., Rumaks, J., Svirskis, S., Mazina, O., Allikalt, A., Rinken, A. et al. (2013) Lunasin-induced behavioural effects in mice: focus on the dopaminergic system. Behavioural Brain Research, 256, 5-9.
Exley, M. A., Hand, L., O'Shea, D., & Lynch, L. (2014). Interplay between the immune system and adipose tissue in obesity. Journal of Endocrinology, 223(2), R41-8.
Faggioni, R., Fantuzzi, G., Fuller, J., Dinarello, C. A., Feingold, K. R., & Grunfeld, C. (1998). IL-1β mediates leptin induction during inflammation. American Journal of Physiology, 274(1), 204-8.
Farooqi, I. S. & O'Rahilly, S. (2009). Leptin: a pivotal regulator of human energy homeostasis. The American Journal of Clinical Nutrition, 89(3), 980S-984S.
Furness, J. B., Kunze, W. A., & Clerc, N. (1999). Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses. American Journal of Physiology, 277(5 Pt 1), G922-8.
Galvez, A. F. (2012). Abstract 10693: Identification of lunasin as the active component in soy protein responsible for reducing LDL cholesterol and risk of cardiovascular disease. Circulation, 26, A10693.
Galvez, A. F., Chen, N., Macasieb, J., & de Lumen, B. O. (2001). Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer Research, 61(20), 7473-8.
García-Nebot, M. J., Recio, I., & Hernández-Ledesma, B. (2014). Antioxidant activity and protective effects of peptide lunasin against oxidative stress in intestinal Caco-2 cells. Food and Chemical Toxicology, 65, 155-61.
Giamila, Fantuzzi. (2005). Adipose tissue, adipokines, and inflammation. Journal of Allergy and Clinical Immunology, 115(5), 911-9.
Gillespie, C., Quarshie, A., Penichet, M., & Gonzalez-Perez, R. R. (2012). Potential Role of Leptin Signaling in DMBA-induced Mammary Tumors by Non-Responsive C57BL/6J Mice Fed a High-Fat Diet. Journal of Carcinogenesis & Mutagenesis, 3(2), 132-141.
Green, H. & Kehinde, M. (1975). An established preadipose cell line and its differentiation in culture.II. Factors affecting the adipose conversion. Cell, 5(1), 19-27.
Gu, J. W., Young, E., Patterson, S. G., Makey, K. L., Wells, J., Huang, M. et al. (2011). Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice. Cancer Biology & Therapy, 11(10), 910-7.
Guijarro-Díez, M., García, M.C., Crego, A.L., & Marina, M.L. (2014). Off-line two dimensional isoelectrofocusing-liquid chromatography/mass spectrometry (time of flight) for the determination of the bioactive peptide lunasin. Journal of Agricultural and Food Chemistry, 1371:117-24.
Hakkak, R., MacLeod, S., Shaaf, S., Holley, A. W., Simpson, P., Fuchs, G. et al. (2007). Obesity increases the incidence of 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in an ovariectomized Zucker rat model. International Journal of Oncology, 30(3), 557-63.
Hariri, N., & Thibault, L. (2010). High-fat diet-induced obesity in animal models. Nutrition Research Reviews, 23(2), 270-99.
Harvey, A. E., Lashinger, L. M, & Hursting, S. D. (2011). The growing challenge of obesity and cancer: an inflammatory issue. Annals of the New York Academy of Sciences, 1229, 45-52.
Hernández-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2009). Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochemical and Biophysical Research Communications, 390(3), 803-8.
Hernández-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2009). Lunasin and Bowman-Birk protease inhibitor (BBI) in US commercial soy foods. Food Chemistry, 115, 574-80.
Hernández-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2013). Chemopreventive properties of Peptide Lunasin: a review. Protein & Peptide Letters, 20(4), 424-32.
Hernández-Ledesma, B., Hsieh, C. C., & de Lumen, B.O. (2009). Lunasin, a novel seed peptide for cancer prevention. Peptides, 30(2), 426-30.
Hirai, S., Kim, Y. I., Goto, T., Kang, M. S., Yoshimura, M., Obata, A. et al. (2007). Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages. Life Sciences, 81(16), 1272-9.
Hsieh, C. C., Hernández-Ledesma, B., & de Lumen, B. O. (2010). Soybean peptide lunasin suppresses in vitro and in vivo 7, 12-dimethylbenz[a]anthracene-induced tumorigenesis. Journal of Food Science, 75(9), H311-6.
Hsieh, C. C., Hernández-Ledesma, B., Jeong, H. J., Park, J. H., & de Lumen, B. O. (2010). Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable. PLOS One, 5(1), e8890.
Hursting, S. D., & Berger, N.A. (2010). Energy balance, host-related factors, and cancer progression. Journal of Clinical Oncology, 28(26), 4058-65.
Hursting, S. D., Lashinger, L. M, Wheatley, K. W., Rogers, C. J., Colbert, L.H, Nunez N. P., et al. (2008). Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link. Best Practice & Research Clinical Endocrinology & Metabolism, 22(4), 659-69.。
Ivanova, E. A., & Orekhov, A. N. (2016). Monocyte Activation in Immunopathology: Cellular Test for Development of Diagnostics and Therapy. Journal of Immunology Research, 4789279.
Janeway, C. AJr., & Medzhitov, R. (2002). Innate immune recognition. Annual Review of Immunology, 20, 197-216.
Jeong, J. B., De Lumen, B. O., & Jeong, H. J. (2010). Lunasin peptide purified from Solanum nigrum L. protects DNA from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction. Cancer Letters, 293(1), 58-64.
Jeong, J.B., Jeong, H. J., Park, J. H., Lee, S. H., Lee, J. R., Lee, H. K. et al. (2007). Cancer preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb). Journal of Agricultural and Food Chemistry, 55(26), 10707-13.
Jia, S., Zhang, S., Yuan, H., & Chen, N. (2015). Lunasin inhibits cell proliferation via apoptosis and reduces the production of proinflammatory cytokines in cultured rheumatoid arthritis synovial fibroblasts. BioMed Research International, 2015,346839.
Jiao, H., Tang, P., & Zhang, Y. (2015). MAP Kinase Phosphatase 2 Regulates Macrophage-Adipocyte Interaction. PLoS One, 10(3), e0120755.
Kaaks, R., Lukanova, A., & Kurzer, M. S. (2002). Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiology, Biomarkers & Prevention, 11(12), 1531-43.
Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R. et al. (2006). MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. Journal of Clinical Investigation, 116(6), 1494-505.
Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R. et al. (2006). MCP1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. Journal of Clinical Investigation, 116, 1494–505.
Kim, J. Y., Kim, T. H., & Kim, S. S. (2008). Anti-inflammatory effect of a human prothrombin fragment-2-derived peptide, NSA9, in EOC2 microglia. Biochemical and Biophysical Research Communications, 368(3), 779-85.
La Cava, A., & Matarese, G. (2004). The weight of leptin in immunity. Nature Reviews Immunology, 4(5), 371-9.
Lam, Q. L., & Lu, L. (2007). Role of leptin in immunity. Cellular & Molecular Immunology, 4(1), 1-13.
Licinio, J., Mantzoros, C., Negrão, A. B., Cizza, G., Wong, M. L., Bongiorno, P.B. et al. (1997). Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nature Medicine, 3(5), 575-9.
Liu, J., Jia, S. H., Kirberger, M., & Chen, N. (2014). Lunasin as a promising health-beneficial peptide. European Review for Medical and Pharmacological Sciences, 18(14), 2070-5.
Loffreda, S., Yang, S. Q., Lin, H. Z., Karp, C. L., Brengman, M. L., Wang, D. J. et al. (1998). Leptin regulates proinflammatory immune responses. The FASEB Journal, 12(1), 57-65.
Lorincz, & A. M., Sukumar, S. (2006). Molecular links between obesity and breast cancer. Endocrine Related Cancer, 13(2), 279-92.
Luca Mazzarella. (2015). Why does obesity promote cancer? Epidemiology, biology, and open questions. Ecancermedicalscience, 9, 554.
Lumeng, C. N, Bodzin, J. L., & Saltiel, A. R. (2007). Obesity induces a phenotypic switch in adipose tissue macrophage polarization. Journal of Clinical Investigation, 117(1), 175-84.
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007). Obesity induces a phenotypic switch in adipose tissue macrophage polarization. Journal of Clinical Investigation, 117(1), 175-84.
Maayah, Z. H., Ghebeh, H., Alhaider, A. A., El-Kadi, A. O., Soshilov, A.A., Denison, M. S., et al. (2015). Metformin inhibits 7, 12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway. Toxicology and Applied Pharmacology, 284(2), 217-26.
Maeda, H., Kanno, S., Kodate, M., Hosokawa, M., & Miyashita, K. (2015). Fucoxanthinol, Metabolite of Fucoxanthin, Improves Obesity-Induced Inflammation in Adipocyte Cells. Marine Drugs, 13(8), 4799–4813.
Majed, F., Rashid, S., Khan, A.Q., Nafees, S., Ali, N., Ali, R., et al. (2015). Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in mice. Molecular and Cellular Biochemistry, 399(1-2), 217-28.
Maury, E., & Brichard, S. M. (2010). Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Molecular and Cellular Endocrinology, 314(1), 1-16.
McArdle, M. A., Finucane, O. M., Connaughton, R. M., McMorrow, A. M., & Roche, H. M. (2013). Mechanisms of Obesity-Induced Inflammation and Insulin Resistance: Insights into the Emerging Role of Nutritional Strategies. Frontiers in Endocrinology, 4, 52.
McConnell, E. J., Devapatla, B., Yaddanapudi, K., Davis, K. R. (2015). The soybean-derived peptide lunasin inhibits non-small cell lung cancer cell proliferation by suppressing phosphorylation of the retinoblastoma protein. Oncotarget, 6(7), 4649-62.
Medzhitov, R., & Janeway, C. A Jr. (1999). Innate immunity: the virtues of a nonclonal system of recognition. Cell, 91(3), 295-8.
Medzhitov, R., & Janeway, C. A. Jr. (1998). Innate immune recognition and control of adaptive immune responses. Seminars in Immunology, 10(5), 351-3.
Mitchell, R. A., Lovegrove, A., & Shewry, P. R. (2013). Lunasin in cereal seeds: What is the origin? Journal of Cereal Science, 57(3), 267-269.
Nakamura, Y., Si, Q. S., & Kataoka, K. (1999). Lipopolysaccharide-induced microglial activation in culture: temporal profiles of morphological change and release of cytokines and nitric oxide. Neuroscience Research, 35(2), 95-100.
Nebert, D. W., Petersen, D. D., & Fornace, A. J. Jr., Nebert, D. W., Petersen, D. D., Fornace, A. J. Jr. et al. (1990). Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm. Environ Health Perspect, 88, 13-25.
Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M. et al. (2009). CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nature Medicine, 15(8), 914-20.
Nolan, E., O'Meara, Y. M., & Godson, C. (2013). Lipid mediators of inflammation in obesity-related glomerulopathy. Nephrology Dialysis Transplantation, 28 Suppl 4, iv22-9.
O'Garra, A. (1998). Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity, 8(3), 275-83.
Ogden, C.L., et al. (2014). Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA, 311(8), 806–14.
Olson, L. K., Tan, Y., Zhao, Y., Aupperlee, M.D., & Haslam, S.Z. (2010). Pubertal exposure to high fat diet causes mouse strain-dependent alterations in mammary gland development and estrogen responsiveness. International Journal of Obesity, 15, 1415–1426.
Ouchi, N., Kihara, S., Funahashi, T., Matsuzawa, Y., & Walsh, K. (2003). Obesity, adiponectin and vascular inflammatory disease. Current Opinion in Lipidology, 14(6), 561-6.
Park, J. H., Jeong, H. J., & de Lumen, B. O. (2005). Contents and bioactivities of lunasin, Bowman-Birk inhibitor, and isoflavones in soybean seed. Journal of Agricultural and Food Chemistry, 53, 7686-90.
Park, J., Morley, T. S., Kim, M., Clegg, D. J., & Scherer, P. E. (2014). Obesity and cancer—mechanisms underlying tumour progression and recurrence. Nature Reviews Endocrinology, 10(8), 455–465.
Parkin, D. M., Boyd, L., & Walker, L. C. (2011). The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. British Journal of Cancer, 105(Suppl 2), S77–S81.
Patsouris, D., Li, P. P., Thapar, D., Chapman, J., Olefsky, J. M., & Neels, J.G. (2008). Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metabolism, 8(4), 301-9.
Paz-Filho, G., Mastronardi, C., Franco, C. B., Wang, K. B., Wong, M. L., & Licinio, J. (2012). Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arquivos Brasileiros de Endocrinologia & Metabologia, 56(9), 597-607.
Pelton, K., Coticchia, C. M., Curatolo, A. S., Schaffner, C. P., Zurakowski, D., Solomon, K. R. et al. (2014). Hypercholesterolemia induces angiogenesis and accelerates growth of breast tumors in vivo. American Journal of Pathology, 184(7), 2099-110.
Raj, D. S. (2009). Role of interleukin-6 in the anemia of chronic disease. Seminars in Arthritis and Rheumatism, 38(5), 382-8.
Ray, A., Nkhata, K. J., & Cleary, M. P. (2007). Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. International Journal of Oncology, 30(6), 1499-509.
Rayalam, S., Della-Fera, M. A., & Baile, C. A. (2008). Phytochemicals and regulation of the adipocyte life cycle. The Journal of Nutritional Biochemistry, 19(11), 717-26.
Rene Gonzalez, R., Watters, A., Xu, Y., Singh, U. P., Mann, D. R., Rueda, B. R. et al. (2009). Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer. Breast Cancer Research, 11(3), R36.
Ron, D., Brasier, A. R., McGehee, R. E. Jr., & Habener, J. F. (1992). Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP). Journal of Clinical Investigation, 89(1), 223-33.
Rose, D. P., & Vona-Davis, L. (2010). Interaction between menopausal status and obesity in affecting breast cancer risk. Maturitas, 66(1), 33-8.
Ruan, H., Hacohen, N., Golub, T. R., Van Parijs, L., & Lodish, H. F. (2002). Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes, 51(5), 1319-36.
Rundle, A., Tang, D., Hibshoosh, H., Estabrook, A., Schnabel, F., Cao, W. et al. (2000). The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer. Carcinogenesis, 21(7), 1281-9.
Seber, L. E., Barnett, B. W., McConnell, E. J., Hume, S. D., Cai, J., Boles, K. et al. (2012). Scalable purification and characterization of the anticancer lunasin peptide from soybean. PLoS One, 7(4), e35409.
Shiri, S., Alizadeh, A. M., Baradaran, B., Farhanghi, B., Shanehbandi, D., Khodayari S. et al. (2015). Dendrosomal curcumin suppresses metastatic breast cancer in mice by changing m1/m2 macrophage balance in the tumor microenvironment. Asian Pacific journal of cancer prevention, 16(9), 3917-22.
Suba, Z. (2003). Circulatory estrogen level protects against breast cancer in obese women. Recent Patents on Anti-Cancer Drug Discovery, 8(2), 154-67.
Suganami, T., Nishida, J., & Ogawa, Y. (2005). A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(10), 2062-8.
Suganami, T., Tanimoto-Koyama, K., Nishida, J., Itoh, M., Yuan, X. et al. (2007). Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(1), 84-91.
Sun, Y., Xie, M., Huang, T., Zhang, X., Lei, S., Shi, Q. et al. (2014). α- Naphthoflavone modulates inflammatory response in adipocytes-macrophages interaction through NFκB signaling. International journal of clinical and experimental pathology, 7(11), 7768-74.
Toren, P., Mora, B. C., Venkateswaran, V. (2013). Diet, obesity, and cancer progression: are adipocytes the link? Lipid Insights, 6, 37-45.
Trombino, A. F., Near, R. I., Matulka, R. A., Yang, S., Hafer, L. J., Toselli, P. A. et al. (2000). Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1 gene transcripts in a rat model of mammary tumorigenesis. Breast Cancer Research and Treatment, 63(2), 117-31.
Turvey, S. E., Broide, D. H. (2010). Innate immunity. Journal of Allergy and Clinical Immunology, 125 (2 Suppl 2), S24-32.
Vaughan, T., & Li, L. (2010). Molecular mechanism underlying the inflammatory complication of leptin in macrophages. Molecular Immunology, 47(15), 2515-8.
Vendrell, J., Broch, M., Vilarrasa, N., Molina, A., Gómez, J. M., Gutiérrez, C. et al. (2004). Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obesity research, 12(6), 962-71.
Villarreal-Molina, M. T., & Antuna-Puente, B. (2012). Adiponectin: anti-inflammatory and cardioprotective effects. Biochimie, 94(10), 2143-9.
Vucenik, I., & Stains, J, P. (2012). Obesity and cancer risk: evidence, mechanisms, and recommendations. Annals of the New York Academy of Sciences, 1271, 37-43.
Wang, B., & Trayhurn, P. (2006). Acute and prolonged effects of TNF-alpha on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture. Pflügers Archiv, 452(4), 418-27.
Wang, C. Y., & Liao, J. K. (2012). A mouse model of diet-induced obesity and insulin resistance. Methods in Molecular Biology, 821, 421-33.
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L. et al. (2003). Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation, 112(12), 1796-808.
White, K. L., Kawabata, T. T., & Ladics, G. S. (1994). Mechanisms of polycyclic aromatic hydrocarbon immunotoxicity. Immunotoxicology and Immunopharmacology, 123–142.
Wu, A. H., Ziegler, R. G., Nomura, A. M., West, D. W., Kolonel, L. N., Horn-Ross, P. L. et al. (1998). Soy intake and risk of breast cancer in Asians and Asian Americans. The American Journal of Clinical Nutrition, 68(6 Suppl), 1437S-1443S.
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., & Chou, C. J. et al. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 112(12), 1821-30.
Yamamoto, S., Sobue, T., Kobayashi, M., Sasaki, S., & Tsugane, S. (2003). Soy, isoflavones, and breast cancer risk in Japan. Journal of the National Cancer Institute, 95(12), 906-13.
Yudkin, J. S., Kumari, M., Humphries, S. E., & Mohamed-Ali, V. (2000). Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis, 148(2), 209-14.
Zarkesh-Esfahani, H., Pockley, A. G., Wu, Z., Hellewell, P. G., Weetman, A. P., & Ross, R. J. (2004). Leptin indirectly activates human neutrophils via induction of TNF-alpha. The Journal of Immunology, 172(3), 1809-14.
Zebisch, K., Voigt, V., Wabitsch, M., & Brandsch, M. (2012). Protocol for effective differentiation of 3T3-L1 cells to adipocytes. Analytical Biochemistry, 425(1), 88-90.
Zhang, L., Shamaladevi, N., Jayaprakasha, G. K., Patil, B. S., & Lokeshwar, B. L. (2015). Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice. Oncotarget, 6(18), 16379-95.
Zhao, Y., Tan, Y. S., Aupperlee, M. D., Langohr, I. M., Kirk, E. L., Troester, M. A. et al. (2013). Pubertal high fat diet: effects on mammary cancer development. Breast Cancer Research, 15(5), R100.
Zhu, Z., Liu, T., Han, F., Zhan, S. D., & Wang, C. Y. (2015). Mutations in the p16 gene in DMBA-induced pancreatic intraepithelial neoplasia and pancreatic cancer in rats. Hepatobiliary & Pancreat
ic Diseases International, 14(2), 208-14.