[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.14348/molcells.2014.0074

Crosstalk between Adipocytes and Immune Cells in Adipose Tissue Inflammation and Metabolic Dysregulation in Obesity

Huh, Jin Young (School of Biological Science, Institute of Molecular Biology and Genetics)
Park, Yoon Jeong (Department of Biophysics and Chemical Biology, Seoul National University)
Ham, Mira (School of Biological Science, Institute of Molecular Biology and Genetics)
Kim, Jae Bum (School of Biological Science, Institute of Molecular Biology and Genetics)

Abstract

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

Keywords

adipocyte; adipose tissue inflammation; antigen presentation; CD1d; CD4 T cell; CD8 T cell; invariant natural killer T cell; macrophage; obesity;

Citations & Related Records

Reference

1	Malide, D., Yewdell, J.W., Bennink, J.R., and Cushman, S.W. (2001). The export of major histocompatibility complex class I molecules from the endoplasmic reticulum of rat brown adipose cells is acutely stimulated by insulin. Mol. Biol. Cell 12, 101-114. DOI
2	Schipper, H.S., Rakhshandehroo, M., van de Graaf, S.F., Venken, K., Koppen, A., Stienstra, R., Prop, S., Meerding, J., Hamers, N., Besra, G., et al. (2012). Natural killer T cells in adipose tissue prevent insulin resistance. J. Clin. Invest. 122, 3343-3354. DOI ScienceOn
3	Shoelson, S.E., Lee, J., and Goldfine, A.B. (2006). Inflammation and insulin resistance. J. Clin. Invest. 116, 1793-1801. DOI ScienceOn
4	Talukdar, S., Oh da, Y., Bandyopadhyay, G., Li, D., Xu, J., McNelis, J., Lu, M., Li, P., Yan, Q., Zhu, Y., et al. (2012). Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat. Med. 18, 1407-1412. DOI ScienceOn
5	Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., and Ferrante, A.W., Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796-1808. DOI
6	Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., et al. (2009). Normalization of obesity-associated insulin resistance through immunotherapy. Nat. Med. 15, 921-929. DOI ScienceOn
7	Winer, D.A., Winer, S., Shen, L., Wadia, P.P., Yantha, J., Paltser, G., Tsui, H., Wu, P., Davidson, M.G., Alonso, M.N., et al. (2011). B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med. 17, 610-617. DOI ScienceOn
8	Hotamisligil, G.S., Shargill, N.S., and Spiegelman, B.M. (1993). Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259, 87-91. DOI ScienceOn
9	Huh, J.Y., Kim, J.I., Park, Y.J., Hwang, I.J., Lee, Y.S., Sohn, J.H., Lee, S.K., Alfadda, A.A., Kim, S.S., Choi, S.H., et al. (2013). A novel function of adipocytes in lipid antigen presentation to iNKT cells. Mol. Cell. Biol. 33, 328-339. DOI
10	Jager, A., and Kuchroo, V.K. (2010). Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand. J. Immunol. 72, 173-184. DOI ScienceOn
11	Ji, Y., Sun, S., Xia, S., Yang, L., Li, X., and Qi, L. (2012). Short-term high-fat-diet challenge promotes alternative macrophage polarization in adipose tissue via natural killer T cells and interleukin-4. J. Biol. Chem. 287, 24378-24386. DOI
12	Lee, Y.S., Li, P., Huh, J.Y., Hwang, I.J., Lu, M., Kim, J.I., Ham, M., Talukdar, S., Chen, A., Lu, W.J., et al. (2011). Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes 60, 2474-2483. DOI ScienceOn
13	Lumeng, C.N., Bodzin, J.L., and Saltiel, A.R. (2007a). Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175-184. DOI ScienceOn
14	Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A.B., Benoist, C., Shoelson, S., et al. (2009). Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15, 930-939. DOI ScienceOn
15	Lumeng, C.N., Deyoung, S.M., Bodzin, J.L., and Saltiel, A.R. (2007b). Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56, 16-23. DOI ScienceOn
16	Bertola, A., Ciucci, T., Rousseau, D., Bourlier, V., Duffaut, C., Bonnafous, S., Blin-Wakkach, C., Anty, R., Iannelli, A., Gugenheim, J., et al. (2012). Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61, 2238-2247. DOI
17	Deng, T., Lyon, C.J., Minze, L.J., Lin, J., Zou, J., Liu, J.Z., Ren, Y., Yin, Z., Hamilton, D.J., Reardon, P.R., et al. (2013). Class II major histocompatibility complex plays an essential role in obesityinduced adipose inflammation. Cell Metab. 17, 411-422. DOI
18	Fulkerson, P.C., and Rothenberg, M.E. (2013). Targeting eosinophils in allergy, inflammation and beyond. Nat. Rev. Drug Dis. 12, 117-129. DOI ScienceOn
19	Gapin, L., Godfrey, D.I., and Rossjohn, J. (2013). Natural killer T cell obsession with self-antigens. Curr. Opin. Immunol. 25, 168-173. DOI ScienceOn
20	Godfrey, D.I., MacDonald, H.R., Kronenberg, M., Smyth, M.J., and Van Kaer, L. (2004). NKT cells: what's in a name? Nat. Rev. Immunol. 4, 231-237. DOI ScienceOn
21	Hackstein, H., and Thomson, A.W. (2004). Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat. Rev. Immunol. 4, 24-34. DOI ScienceOn
22	Bornstein, S.R., Abu-Asab, M., Glasow, A., Path, G., Hauner, H., Tsokos, M., Chrousos, G.P., and Scherbaum, W.A. (2000). Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. Diabetes 49, 532-538. DOI ScienceOn
23	Ham, M., Lee, J.W., Choi, A.H., Jang, H., Choi, G., Park, J., Kozuka, C., Sears, D.D., Masuzaki, H., and Kim, J.B. (2013). Macrophage glucose-6-phosphate dehydrogenase stimulates proinflammatory responses with oxidative stress. Mol. Cell. Biol. 33, 2425-2435. DOI ScienceOn
24	Pham, C.T. (2006). Neutrophil serine proteases: specific regulators of inflammation. Nat. Rev. Immunol. 6, 541-550. DOI ScienceOn
25	Bischoff, S.C. (2007). Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat. Rev. Immunol. 7, 93-104. DOI ScienceOn
26	Brennan, P.J., Brigl, M., and Brenner, M.B. (2013). Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat. Rev. Immunol. 13, 101-117. DOI ScienceOn
27	Chawla, A., Nguyen, K.D., and Goh, Y.P. (2011). Macrophagemediated inflammation in metabolic disease. Nat. Rev. Immunol. 11, 738-749. DOI ScienceOn
28	Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S.E., Benoist, C., and Mathis, D. (2012). PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486, 549-553.
29	Mantell, B.S., Stefanovic-Racic, M., Yang, X., Dedousis, N., Sipula, I.J., and O'Doherty, R.M. (2011). Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS One 6, e19831. DOI
30	Mathis, D. (2013). Immunological goings-on in visceral adipose tissue. Cell Metab. 17, 851-859. DOI ScienceOn
31	Moller, D.E., and Kaufman, K.D. (2005). Metabolic syndrome: a clinical and molecular perspective. Annu. Rev. Med. 56, 45-62. DOI ScienceOn
32	Morris, D.L., Cho, K.W., Delproposto, J.L., Oatmen, K.E., Geletka, L.M., Martinez-Santibanez, G., Singer, K., and Lumeng, C.N. (2013). Adipose tissue macrophages function as antigenpresenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes 62, 2762-2772. DOI ScienceOn
33	Nijhuis, J., Rensen, S.S., Slaats, Y., van Dielen, F.M., Buurman, W.A., and Greve, J.W. (2009). Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity (Silver Spring) 17, 2014-2018. DOI ScienceOn
34	Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009). CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15, 914-920. DOI ScienceOn
35	Nishimura, S., Manabe, I., Takaki, S., Nagasaki, M., Otsu, M., Yamashita, H., Sugita, J., Yoshimura, K., Eto, K., Komuro, I., et al. (2013). Adipose natural regulatory B cells negatively control adipose tissue inflammation. Cell Metab. pii: S1550-4131(13)00386-0.
36	Ouchi, N., Parker, J.L., Lugus, J.J., and Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11, 85-97. DOI ScienceOn
37	Patsouris, D., Li, P.P., Thapar, D., Chapman, J., Olefsky, J.M., and Neels, J.G. (2008). Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 8, 301-309. DOI ScienceOn
38	Xu, H., Barnes, G.T., Yang, Q., Tan, G., Yang, D., Chou, C.J., Sole, J., Nichols, A., Ross, J.S., Tartaglia, L.A., et al. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821-1830. DOI ScienceOn
39	Wu, D., Molofsky, A.B., Liang, H.E., Ricardo-Gonzalez, R.R., Jouihan, H.A., Bando, J.K., Chawla, A., and Locksley, R.M. (2011). Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332, 243-247. DOI ScienceOn
40	Wu, L., Parekh, V.V., Gabriel, C.L., Bracy, D.P., Marks-Shulman, P.A., Tamboli, R.A., Kim, S., Mendez-Fernandez, Y.V., Besra, G.S., Lomenick, J.P., et al. (2012). Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice. Proc. Natl. Acad. Sci. USA 109, E1143-1152. DOI
41	Yang, H., Youm, Y.H., Vandanmagsar, B., Ravussin, A., Gimble, J.M., Greenway, F., Stephens, J.M., Mynatt, R.L., and Dixit, V.D. (2010). Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. J. Immunol. 185, 1836-1845. DOI ScienceOn
42	Zhu, J., and Paul, W.E. (2008). CD4 T cells: fates, functions, and faults. Blood 112, 1557-1569. DOI ScienceOn
43	Lynch, L., Nowak, M., Varghese, B., Clark, J., Hogan, A.E., Toxavidis, V., Balk, S.P., O'Shea, D., O'Farrelly, C., and Exley, M.A. (2012). Adipose tissue invariant NKT cells protect against dietinduced obesity and metabolic disorder through regulatory cytokine production. Immunity 37, 574-587. DOI ScienceOn
44	Uldrich, A.P., Le Nours, J., Pellicci, D.G., Gherardin, N.A., McPherson, K.G., Lim, R.T., Patel, O., Beddoe, T., Gras, S., Rossjohn, J., et al. (2013). CD1d-lipid antigen recognition by the gammadelta TCR. Nat. Immunol. 14, 1137-1145. DOI ScienceOn
45	Liu, J., Divoux, A., Sun, J., Zhang, J., Clement, K., Glickman, J.N., Sukhova, G.K., Wolters, P.J., Du, J., Gorgun, C.Z., et al. (2009). Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15, 940-945. DOI ScienceOn
46	Rocha, V.Z., Folco, E.J., Sukhova, G., Shimizu, K., Gotsman, I., Vernon, A.H., and Libby, P. (2008). Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ. Res. 103, 467-476. DOI ScienceOn
47	Amano, S.U., Cohen, J.L., Vangala, P., Tencerova, M., Nicoloro, S.M., Yawe, J.C., Shen, Y., Czech, M.P., and Aouadi, M. (2014). Local proliferation of macrophages contributes to obesityassociated adipose tissue inflammation. Cell Metab. 19, 162-171. DOI ScienceOn

Reference

	Thea Magrone. (2015) Frontiers in Immunology Childhood Obesity: Immune Response and Nutritional Approaches / 6
	Alexander Kalinkovich. (2017) Ageing Research Reviews Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis / 35 , 200
2	N. Molina. (2015) International Immunopharmacology Green tea polyphenols change the profile of inflammatory cytokine release from lymphocytes of obese and lean rats and protect against oxidative damage / 28 (2) , 985
1	Arturo Roca-Rivada. (2015) Scientific Reports CILAIR-Based Secretome Analysis of Obese Visceral and Subcutaneous Adipose Tissues Reveals Distinctive ECM Remodeling and Inflammation Mediators / 5 (1)
	Yi Zhang. (2015) International Journal of Endocrinology Eosinophils Reduce Chronic Inflammation in Adipose Tissue by Secreting Th2 Cytokines and Promoting M2 Macrophages Polarization / 2015 , 1
2	Darlene E. Berryman. (2016) Expert Review of Endocrinology & Metabolism Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: implications to the clinic / 11 (2) , 197
5	Manuel Picon-Ruiz. (2017) CA: A Cancer Journal for Clinicians Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention / 67 (5) , 378
	Giulia Maurizi. (2018) Journal of Cellular Physiology Adipocytes properties and crosstalk with immune system in obesity-related inflammation /
9	Antonella Poloni. (2015) Cytotherapy Interaction between human mature adipocytes and lymphocytes induces T-cell proliferation / 17 (9) , 1292
1-2	Kalyana C. Nandipati. (2017) Molecular and Cellular Biochemistry Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance / 426 (1-2) , 27
4	Jin Young Huh. (2017) Diabetes Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity / 66 (4) , 835
4	Sandeep Sundara Rajan. (2016) Immunology Dendritic cells and adipose tissue / 149 (4) , 353
1	Yaqin Zhang. (2015) Nutrition & Metabolism Inflamed macrophage microvesicles induce insulin resistance in human adipocytes / 12 (1)
4	Solange S. Pereira. (2014) Current Obesity Reports Low-Grade Inflammation, Obesity, and Diabetes / 3 (4) , 422
9	Cécile Martinerie. (2016) Diabetes NOV/CCN3: A New Adipocytokine Involved in Obesity-Associated Insulin Resistance / 65 (9) , 2502
	Sung Sik Choe. (2016) Frontiers in Endocrinology Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders / 7
8	Jonathan M. Nizar. (2017) Current Hypertension Reports Molecular Mechanisms of Sodium-Sensitive Hypertension in the Metabolic Syndrome / 19 (8)
20	B C S Boa. (2017) British Journal of Pharmacology Exercise effects on perivascular adipose tissue: endocrine and paracrine determinants of vascular function / 174 (20) , 3466
	Leszek Szablewski. (2016) International Journal of Diabetes in Developing Countries From obesity through immunity to type 2 diabetes mellitus /
9	Christopher G. Bell. (2017) Obesity The Epigenomic Analysis of Human Obesity / 25 (9) , 1471
	I.V. Wagner. (2016) Molecular and Cellular Endocrinology Prepubertal onset of obesity negatively impacts on testicular steroidogenesis in rats / 437 , 154
4	Xiaoqian Hu. (2016) Journal of Lipid Research Major role of adipocyte prostaglandin E2in lipolysis-induced macrophage recruitment / 57 (4) , 663
2	Masuko Kobori. (2016) Molecular Nutrition & Food Research Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet-induced obese mice / 60 (2) , 300
9	Aleida Núñez Ruiz. (2016) Nutrition Diminished levels of regulatory T cell subsets (CD8+Foxp3, CD4+Foxp3 and CD4+CD39+Foxp3) but increased Foxp3 expression in adipose tissue from overweight subjects / 32 (9) , 943
9	Lina Badimon. (2017) Cardiovascular Research Adipose tissue depots and inflammation: effects on plasticity and resident mesenchymal stem cell function / 113 (9) , 1064
	Konstanze Zieger. (2018) Molecular and Cellular Endocrinology Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFκB pathway /
	Emanuel Fabersani. (2017) Frontiers in Immunology Specific Strains of Lactic Acid Bacteria Differentially Modulate the Profile of Adipokines In Vitro / 8
1	Sudharsana R. Ande. (2016) Scientific Reports Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC / 6 (1)
2	Yoon Jeong Park. (2017) Adipocyte The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in obesity / 6 (2) , 147
	Geir Bjørklund. (2017) Nutrition Role of oxidative stress and antioxidants in daily nutrition and human health / 33 , 311
2	Sivan Cohen. (2017) European Journal of Immunology Nutritional effects on T-cell immunometabolism / 47 (2) , 225
8	Masanori Katsumura. (2017) Animal Science Journal Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice / 88 (8) , 1100
1	Hun Soo Chang. (2017) Expert Review of Respiratory Medicine Neutrophilic inflammation in asthma: mechanisms and therapeutic considerations / 11 (1) , 29
	Valerie A. Gerriets. (2014) Frontiers in Immunology Role of T Cells in Malnutrition and Obesity / 5
4	Zheng-mei Lv. (2015) Molecular Reproduction and Development Resveratrol attenuates inflammation and oxidative stress in epididymal white adipose tissue: Implications for its involvement in improving steroidogenesis in diet-induced obese mice / 82 (4) , 321
	K. S. Petersen. (2016) Oxidative Medicine and Cellular Longevity Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products from Grapes / 2016 , 1
	Soumaya Kouidhi. (2016) Frontiers in Immunology Intrinsic and Tumor Microenvironment-Induced Metabolism Adaptations of T Cells and Impact on Their Differentiation and Function / 7
12	(2015) Molecules and Cells TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways / 38 (12) , 1037
10	Lei Zhang. (2016) Diabetologia Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages / 59 (10) , 2219
4	Dong-Mei Zhang. (2017) Nutrients High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions / 9 (4) , 335
10	Bastien Vergoni. (2016) Diabetes DNA Damage and the Activation of the p53 Pathway Mediate Alterations in Metabolic and Secretory Functions of Adipocytes / 65 (10) , 3062
	Ying Huang. (2016) Disease Markers Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure / 2016 , 1
4	Agnieszka Irena Mazur-Bialy. (2017) International Journal of Molecular Sciences Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation / 18 (4) , 701
1	Ahmed Bakillah. (2016) Nutrition & Metabolism Mice subjected to aP2-Cre mediated ablation of microsomal triglyceride transfer protein are resistant to high fat diet induced obesity / 13 (1)
7	Gina Song. (2016) Nanomedicine: Nanotechnology, Biology and Medicine Gulp1 is associated with the pharmacokinetics of PEGylated liposomal doxorubicin (PLD) in inbred mouse strains / 12 (7) , 2007
2	J.C.J. van Esterik. (2015) Toxicology and Applied Pharmacology Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153 / 289 (2) , 262
1	Abhishek Sanyal. (2017) Cell Reports Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue / 18 (1) , 225
12	(2017) Nutrients Integrated Immunomodulatory Mechanisms through which Long-Chain n-3 Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction / 9 (12) , 1289
8	(2014) Arteriosclerosis, Thrombosis, and Vascular Biology Proinflammatory Phenotype of Perivascular Adipocytes / 34 (8) , 1631
9	(2015) Physiological Reports Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice / 3 (9) , e12534
1664-8021	(2018) Frontiers in Genetics Type 1 Diabetes Mellitus-Associated Genetic Variants Contribute to Overlapping Immune Regulatory Networks / 9 (1664-8021)
1	(2018) Cardiovascular Diabetology Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword / 17 (1)
4	(2018) American Journal of Physiology-Endocrinology and Metabolism Protectin DX attenuates LPS-induced inflammation and insulin resistance in adipocytes via AMPK-mediated suppression of the NF-κB pathway / 315 (4) , E543
2162-397X	(2017) Adipocyte Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization / (2162-397X) , 1
2	(2018) Nature Reviews Nephrology Immunologic and endocrine functions of adipose tissue: implications for kidney disease / 14 (2) , 105
2	(2017) Immunology Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis / 153 (2) , 179
1	(2018) Scientific Reports Neutralization of IL-15 abrogates experimental immune-mediated cholangitis in diet-induced obese mice / 8 (1)
2	(2018) Seminars in Immunopathology Immunometabolism, pregnancy, and nutrition / 40 (2) , 157
1664-3224	(2018) Frontiers in Immunology Innate Lymphocytes in Adipose Tissue Homeostasis and Their Alterations in Obesity and Colorectal Cancer / 9 (1664-3224)
7	(2018) Metabolic Syndrome and Related Disorders Peripheral Lymphocytes, Obesity, and Metabolic Syndrome in Young Adults: An Immunometabolism Study / 16 (7) , 342
8	(2018) Arteriosclerosis, Thrombosis, and Vascular Biology Emerging Roles for Adipose Tissue in Cardiovascular Disease / 38 (8)
1664-3224	(2018) Frontiers in Immunology Changes in Nutritional Status Impact Immune Cell Metabolism and Function / 9 (1664-3224)
5	(2018) PLOS ONE Dietary yeast-derived mannan oligosaccharides have immune-modulatory properties but do not improve high fat diet-induced obesity and glucose intolerance / 13 (5) , e0196165
1	(2018) Journal of Molecular Endocrinology LECT2 promotes inflammation and insulin resistance in adipocytes via P38 pathways / 61 (1) , 37
3	(2018) IUBMB Life and IL-10 mRNA levels in the peripheral blood of breast cancer patients / 70 (3) , 237
9	(2018) Obesity Surgery Tissue-Specific Phenotype and Activation of iNKT Cells in Morbidly Obese Subjects: Interaction with Adipocytes and Effect of Bariatric Surgery / 28 (9) , 2774
7	(2018) International Journal of Molecular Sciences PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity / 19 (7) , 2124
4	(2018) Inflammation Microenvironment of Immune Cells Within the Visceral Adipose Tissue Sensu Lato vs. Epicardial Adipose Tissue: What Do We Know? / 41 (4) , 1142
1466-1861	(2018) Mediators of Inflammation Regulation of Metabolic Disease-Associated Inflammation by Nutrient Sensors / 2018 (1466-1861) , 1
1664-042X	(2018) Frontiers in Physiology Obesity, Fat Mass and Immune System: Role for Leptin / 9 (1664-042X)
1664-3224	(2018) Frontiers in Immunology Regulatory Roles of Invariant Natural Killer T Cells in Adipose Tissue Inflammation: Defenders Against Obesity-Induced Metabolic Complications / 9 (1664-3224)
1466-1861	(2019) Mediators of Inflammation Cells / 2019 (1466-1861) , 1
9	(2016) The Journal of clinical endocrinology & metabolism Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation / 101 (9) , 3469
12	(2018) British Journal of Nutrition Dietary supplementation with blueberry partially restores T-cell-mediated function in high-fat-diet-induced obese mice / 119 (12) , 1393
10	(2018) British Journal of Pharmacology Adipokines and inflammation: is it a question of weight? / 175 (10) , 1569
1	(2018) Journal of Biomedical Science β-aminoisobutyric acid attenuates LPS-induced inflammation and insulin resistance in adipocytes through AMPK-mediated pathway / 25 (1)
4	(2018) International Journal of Molecular Sciences Macrophage Populations in Visceral Adipose Tissue from Pregnant Women: Potential Role of Obesity in Maternal Inflammation / 19 (4) , 1074
2162-397X	(2018) Adipocyte Adipocyte CD1d determines adipose inflammation and insulin resistance in obesity / (2162-397X) , 1
1476-5497	(2019) International Journal of Obesity Ileal transcriptome analysis in obese rats induced by high-fat diets and an adenoviral infection / (1476-5497)
2162-397X	(2019) Adipocyte Higher lactate production from glucose in cultured adipose nucleated stromal cells than for rat adipocytes / (2162-397X) , 1
3	(2019) Applied Physiology, Nutrition, and Metabolism High-fat diet leads to adiposity and adipose tissue inflammation: the effect of whey protein supplementation and aerobic exercise training / 44 (3) , 255
15	(2014) Journal of Cancer Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation / 7 (15) , 2346
15	(2014) Journal of Cancer Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation / 7 (15) , 2346
3	(2014) Serbian journal of experimental and clinical research Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet / 17 (3) , 231
9	(2018) The Journal of clinical endocrinology & metabolism Subcutaneous Fat Fibrosis Links Obesity to Insulin Resistance in Chinese Americans / 103 (9) , 3194
None	(2014) Mediators of inflammation Cigarette Smoking and Adipose Tissue: The Emerging Role in Progression of Atherosclerosis / 2017 (None) , 3102737
None	(2014) Frontiers in immunology Natural Killer Cells from the Subcutaneous Adipose Tissue Underexpress the NKp30 and NKp44 in Obese Persons and Are Less Active against Major Histocompatibility Complex Class I Non-Expressing Neoplast / 8 (None) , 1486
1	(2017) Genes & nutrition Impact of supplementation with a food-derived microbial community on obesity-associated inflammation and gut microbiota composition / 12 (1) , 25
10	(2014) Molecules and cells Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis / 41 (10) , 900
None	(2014) OncoTargets and therapy Albumin/globulin ratio is negatively correlated with PD-1 and CD25 mRNA levels in breast cancer patients / 11 (None) , 2131
14	(2014) International journal of medical sciences Infrequent Feeding of Restricted Amounts of Food Induces Stress and Adipose Tissue Inflammation, Contributing to Impaired Glucose Metabolism / 15 (14) , 1667
2	(2014) Hormone Molecular Biology and Clinical Investigation Obesity associated disease risk: the role of inherent differences and location of adipose depots / 33 (2) , 20180012
2	(2014) Hormone Molecular Biology and Clinical Investigation Obesity associated disease risk: the role of inherent differences and location of adipose depots / 33 (2) , 20180012
5	(2014) JCI insight CD8+ T cells in beige adipogenesis and energy homeostasis / 3 (5) , e95456
5	(2014) JCI insight CD8+ T cells in beige adipogenesis and energy homeostasis / 3 (5) , e95456
27	(2018) Medicine Association between serum leptin levels and breast cancer risk : An updated systematic review and meta-analysis / 97 (27) , e11345
None	(2014) Metabolism : clinical and experimental Depletion of dendritic cells in perivascular adipose tissue improves arterial relaxation responses in type 2 diabetic mice / 85 (None) , 76
12	(2018) PLoS ONE A long-term maternal diet transition from high-fat diet to normal fat diet during pre-pregnancy avoids adipose tissue inflammation in next generation / 13 (12) , e0209053
50	(2014) ACS applied materials & interfaces Resveratrol Delivery from Porous Poly(lactide-<I>co</I>-glycolide) Scaffolds Promotes an Anti-Inflammatory Environment within Visceral Adipose Tissue / 10 (50) , 43363
9	(2014) Klinicheskaia meditsina The role of system inflammation in bronchial asthma and obesity / 96 (9) , 784
4	(2019) BMC bioinformatics Integration of transcriptomic data in a genome-scale metabolic model to investigate the link between obesity and breast cancer / 20 (4) , 162
1	(2014) International journal of medical sciences Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression / 16 (1) , 167
None	(2014) Oxidative medicine and cellular longevity Flavonoids from <I>Apios americana</I> Medikus Leaves Protect RAW264.7 Cells against Inflammation via Inhibition of MAPKs, Akt-mTOR Pathways, and Nfr2 Activation / 2019 (None) , 1563024
None	(2014) Frontiers in Endocrinology Type 2 Diabetes: How Much of an Autoimmune Disease? / 10 (None) , 451
None	(2014) Frontiers in cell and developmental biology Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization / 7 (None) , 329
3	(2019) American journal of physiology, Endocrinology and metabolism Increased mast cell abundance in adipose tissue of metabolic syndrome: relevance to the proinflammatory state and increased adipose tissue fibrosis / 316 (3) , E504
1	(2014) Biology Targeting White Adipose Tissue with Exercise or Bariatric Surgery as Therapeutic Strategies in Obesity / 8 (1) , 16
4	(2019) Annals of oncology : official journal of the European Society for Medical Oncology Meeting report from the joint IARC–NCI international cancer seminar series: a focus on colorectal cancer / 30 (4) , 510
4	(2014) The FASEB journal : official publication of the Federation of American Societies for Experimental Biology In vivo screening of multiple bacterial strains identifies Lactobacillus rhamnosus Lb102 and Bifidobacterium animalis ssp. lactis Bf141 as probiotics that improve metabolic disorders in a mouse model / 33 (4) , 4921
8	(2014) International journal of molecular sciences Molecular Relationships among Obesity, Inflammation and Intervertebral Disc Degeneration: Are Adipokines the Common Link? / 20 (8) , 2030
8	(2019) Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research Inflammation and Immunity: From an Adipocyte's Perspective / 39 (8) , 459
9	(2014) International journal of molecular sciences Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications / 20 (9) , 2358
3	(2014) Aging cell Long‐term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity / 18 (3) , e12948
None	(2014) European journal of pharmacology Role of brown adipose tissue in modulating adipose tissue inflammation and insulin resistance in high-fat diet fed mice / 854 (None) , 354
8	(2019) Cells Immune-Deficient Pfp/Rag2-/- Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice / 8 (8) , 775
8	(2014) Nutrients The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity / 11 (8) , 1943
6	(2014) Oral diseases Immune‐related gene expression profiles of hypothermia adipocytes: Implications for Bell's palsy / 25 (6) , 1652
11	(2014) Current diabetes reports De Novo Lipogenesis as a Source of Second Messengers in Adipocytes / 19 (11) , 138
12	(2014) International journal of rheumatic diseases Serum leptin, a potential predictor of long‐term angiographic progression in Takayasu’s arteritis / 22 (12) , 2134
23	(2014) Genes & development Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity / 33 (23) , 1657
4	(2020) Jb & js open access The Effect of Body Mass Index Class on Patient-Reported Health-Related Quality of Life Before and After Total Hip Arthroplasty for Osteoarthritis : Registry-Based Cohort Study of 64,055 Patients / 5 (4) , e20.00100
1	(2020) Cellular and molecular life sciences : CMLS Adipocyte-progenitor cell communication that influences adipogenesis / 77 (1) , 115
None	(2014) Frontiers in Endocrinology Cytokine Output of Adipocyte-iNKT Cell Interplay Is Skewed by a Lipid-Rich Microenvironment / 11 (None) , 479
None	(2020) Frontiers in aging neuroscience Aging Reduces Estradiol Protection Against Neural but Not Metabolic Effects of Obesity in Female 3xTg-AD Mice / 12 (None) , 113
2	(2014) Women & health Can body mass index identify cardiac autonomic dysfunction in women who are apparently healthy? / 60 (2) , 168
7	(2014) Gastroenterology Adipose Tissue-Liver Cross Talk in the Control of Whole-Body Metabolism: Implications in Nonalcoholic Fatty Liver Disease / 158 (7) , 1899
5	(2014) Arteriosclerosis, thrombosis, and vascular biology B Lymphocytes and Adipose Tissue Inflammation / 40 (5) , 1110
6	(2014) International journal of obesity : journal of the International Association for the Study of Obesity What we know and what we need to know about adenovirus 36-induced obesity / 44 (6) , 1197
11	(2014) Molecules The Targeted Impact of Flavones on Obesity-Induced Inflammation and the Potential Synergistic Role in Cancer and the Gut Microbiota / 25 (11) , 2477
6	(2020) Bioscience reports Adipose stem cells in obesity: challenges and opportunities / 40 (6) , BSR20194076
7	(2020) Journal of neurology: Zeitschrift für Neurologie The etiology of Bell’s palsy: a review / 267 (7) , 1896
8	(2014) Clinical and experimental pharmacology & physiology EoTHINophils: Eosinophils as key players in adipose tissue homeostasis / 47 (8) , 1495
8	(2014) Cancers Single-Cell RNA-seq Reveals Obesity-Induced Alterations in the <I>Brca1</I> -Mutated Mammary Gland Microenvironment / 12 (8) , 2235
16	(2014) International journal of molecular sciences Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics / 21 (16) , 5793
8	(2014) Plants The Effects of Triterpenoid Saponins from the Seeds of <I>Momordica cochinchinensis</I> on Adipocyte Differentiation and Mature Adipocyte Inflammation / 9 (8) , 984
9	(2014) Biology Factors Associated with Increased Morbidity and Mortality of Obese and Overweight COVID-19 Patients / 9 (9) , 280
9	(2020) Molecules and cells Classifying the Linkage between Adipose Tissue Inflammation and Tumor Growth through Cancer-Associated Adipocytes / 43 (9) , 763
7	(2014) Pancreatology : official journal of the International Association of Pancreatology ... [et al.] Class III obesity rather than metabolic syndrome impacts clinical outcomes of acute pancreatitis: A propensity score weighted analysis / 20 (7) , 1287
46	(2014) Journal of agricultural and food chemistry Combined Effect of Quercetin and Fish Oil on Oxidative Stress in the Liver of Mice Fed a Western-Style Diet / 68 (46) , 13267
3	(2020) Cell Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans / 183 (3) , 666
None	(2020) Molecular and cellular endocrinology Administration of kynurenic acid reduces hyperlipidemia-induced inflammation and insulin resistance in skeletal muscle and adipocytes / 518 (None) , 110928
1	(2014) BMC pulmonary medicine Association between tumor necrosis factor alpha and obstructive sleep apnea in adults: a meta-analysis update / 20 (1) , 215
1	(2014) Journal of translational medicine Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues / 18 (1) , 433
23	(2014) International journal of molecular sciences Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity / 21 (23) , 9091
6	(2014) Cell metabolism TANK-Binding Kinase 1 Regulates the Localization of Acyl-CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation / 32 (6) , 1012
6	(2014) International reviews of immunology Pregnancy immune tolerance at the maternal-fetal interface / 39 (6) , 247
None	(2014) Pharmacogenomics and personalized medicine Isotretinoin Induced Hyperlipidemia and Impact of Leptin Gene rs 7799039 Polymorphism in Safety of Acne Patients / 14 (None) , 1679
2	(2014) International journal of molecular sciences The Interplay between Angiopoietin-Like Proteins and Adipose Tissue: Another Piece of the Relationship between Adiposopathy and Cardiometabolic Diseases? / 22 (2) , 742
None	(2021) Frontiers in neuroscience Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior / 15 (None) , 631311
1	(2014) Biomolecules & therapeutics The Role of Leptin in the Association between Obesity and Psoriasis / 29 (1) , 11
None	(2014) Journal of diabetes research SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence / 2021 (None) , 1
None	(2014) Immunity & ageing Obesity and COVID-19: what makes obese host so vulnerable? / 18 (None) , 1
None	(2021) Frontiers in immunology Adipocytes Are the Control Tower That Manages Adipose Tissue Immunity by Regulating Lipid Metabolism / 11 (None) , 598566
None	(2014) Frontiers in immunology The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease / 11 (None) , 622468
None	(2021) Frontiers in physiology Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells / 11 (None) , 624903
1	(2021) Adipocyte Swertiamarin supplementation prevents obesity-related chronic inflammation and insulin resistance in mice fed a high-fat diet / 10 (1) , 160
None	(2014) Frontiers in immunology Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs / 12 (None) , 744022
1	(2014) European journal of clinical nutrition The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth / 75 (1) , 180
None	(2014) Frontiers in nutrition : FNUT Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue / 8 (None) , 675935
None	(2021) Frontiers in Endocrinology The Role of Brown Adipose Tissue Dysfunction in the Development of Cardiovascular Disease / 12 (None) , 652246
1	(2014) Immunity, Inflammation and Disease Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease / 9 (1) , 59
3	(2014) American journal of physiology, Endocrinology and metabolism Is nuclear sirtuin SIRT6 a master regulator of immune function? / 320 (3) , E399
None	(2021) Nanomedicine : nanotechnology, biology and medicine Improved insulin sensitivity in obese-diabetic mice <I>via</I> chitosan Nanomicelles mediated silencing of pro-inflammatory Adipocytokines / 33 (None) , 102357
5	(2014) American journal of physiology, Gastrointestinal and liver physiology Recent advances and health implications of dietary fasting regimens on the gut microbiome / 320 (5) , G847
6	(2014) The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Mechanical overload‐induced muscle‐derived extracellular vesicles promote adipose tissue lipolysis / 35 (6) , None
7	(2014) Cells Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response / 10 (7) , 1738
6	(2014) Biology The Peculiar Trialogue between Pediatric Obesity, Systemic Inflammatory Status, and Immunity / 10 (6) , 512
6	(2021) Cells Towards Goals to Refine Prophylactic and Therapeutic Strategies Against COVID-19 Linked to Aging and Metabolic Syndrome / 10 (6) , 1412
3	(2021) Experimental and therapeutic medicine Palmitic acid up regulates Gal‑3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF‑κB / 22 (3) , 1028
7	(2014) Life Inflammation in Metabolic and Cardiovascular Disorders-Role of Oxidative Stress / 11 (7) , 672
12	(2014) Critical reviews in food science and nutrition Natural constituents from food sources as therapeutic agents for obesity and metabolic diseases targeting adipose tissue inflammation / 61 (12) , 1947
16	(2014) Natural product research Anti-adipogenic and anti-oxidant effects of a standardised extract of Moro blood oranges (<I>Citrus sinensis</I> (L.) Osbeck) during adipocyte differentiation of 3T3-L1 preadipocytes / 35 (16) , 2660
None	(2014) Ageing research reviews Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration / 70 (None) , 101397
18	(2021) International journal of environmental research and public health Estrogen-Receptor-Positive Breast Cancer in Postmenopausal Women: The Role of Body Composition and Physical Exercise / 18 (18) , 9834
5	(2014) The Journal of biological chemistry Emerging roles of epigenetic regulation in obesity and metabolic disease / 297 (5) , 101296
11	(2014) Experimental & molecular medicine : EMM Roles of IκB kinases and TANK-binding kinase 1 in hepatic lipid metabolism and nonalcoholic fatty liver disease / 53 (11) , 1697
1	(2014) BMC biology Adipoclast: a multinucleated fat-eating macrophage / 19 (1) , 246
12	(2014) Cells CXCL16/CXCR6 Axis in Adipocytes Differentiated from Human Adipose Derived Mesenchymal Stem Cells Regulates Macrophage Polarization / 10 (12) , 3410
12	(2014) Cells Exercise Inhibits NLRP3 Inflammasome Activation in Obese Mice via the Anti-Inflammatory Effect of Meteorin-like / 10 (12) , 3480
2	(2014) Biochimica et biophysica acta. Molecular basis of disease Prominent hypertrophy of perivascular adipocytes due to short-term high fat diet / 1868 (2) , 166315