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Sun-O Ka Department of Biochemistry, College of Pharmacy, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeonbuk 561-756, Republic of Korea

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Mi-Young Song Department of Biochemistry, College of Pharmacy, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeonbuk 561-756, Republic of Korea

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Eun Ju Bae Department of Biochemistry, College of Pharmacy, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeonbuk 561-756, Republic of Korea

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Byung-Hyun Park Department of Biochemistry, College of Pharmacy, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeonbuk 561-756, Republic of Korea

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tissues and the consequent tissue inflammation are responsible for obesity-related insulin resistance. Macrophages are infiltrating immune cells that are central to initiating and orchestrating obesity-induced local inflammation. The importance of

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Zhenguang Zhang University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Agnes E Coutinho University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Tak Yung Man University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Tiina M J Kipari Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK

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Patrick W F Hadoke University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Donald M Salter Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK

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Jonathan R Seckl University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Karen E Chapman University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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arthritis, the role of endogenous corticosteroids in regulating inflammation is less well understood ( Coutinho & Chapman 2011 ). Nevertheless, macrophages have emerged as a key target for the anti-inflammatory and immunomodulatory effects of endogenous

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AnneMarie Gagnon Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6
Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6

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Charlie Foster Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6
Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6

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Anne Landry Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6
Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6

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Alexander Sorisky Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6
Chronic Disease Program, Departments of Medicine and of Biochemistry, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6

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Introduction Obesity-associated insulin resistance is related to adipose tissue inflammation, characterized by macrophage infiltration and altered adipose tissue remodeling, including adipocyte hypertrophy ( Weisberg et al . 2003 , Xu et al

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Ya Pei Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Honggui Li Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Yuli Cai Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China

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Jing Zhou Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Xianjun Luo Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Linqiang Ma Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Kelly McDaniel Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Tianshu Zeng Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Yanming Chen Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Xiaoxian Qian Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China

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Shannon Glaser Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Fanyin Meng Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Gianfranco Alpini Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Lulu Chen Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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effective approaches for treatment and/or prevention of obesity-associated metabolic diseases. Since the discovery of macrophage infiltration in adipose tissue of mice with diet-induced obesity (DIO) ( Weisberg et al. 2003 , Xu et al. 2003 ), a

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Jing Zhou Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Honggui Li Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Yuli Cai Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Department of Endocrinology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China

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Linqiang Ma Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
The Laboratory of Lipid & Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Destiny Matthews Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Bangchao Lu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Department of Geriatrics, Nanjing Drum Tower Hospital, the Affiliated Nanjing Hospital of Nanjing University Medical School, Nanjing, Jiangshu, China

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Bilian Zhu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Yanming Chen Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Xiaoxian Qian Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Xiaoqiu Xiao The Laboratory of Lipid & Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Qifu Li Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Shaodong Guo Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Liang Zhao Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China

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Yanan Tian Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, Texas, USA

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Qingsheng Li Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA

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Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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such as macrophages and neutrophils ( Gessi et al. 2000 , Haskó et al. 2008 ). Previous studies have validated a critical role for A 2A R in the pathophysiology of NAFLD/NASH. Specifically, A 2A R activation is shown to ameliorate NASH phenotype in

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Mingjuan Deng Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China

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Fang Qu Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China

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Long Chen Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Chang Liu Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China

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Ming Zhang School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing, China

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Fazheng Ren Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Huiyuan Guo Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Hao Zhang Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China

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Shaoyang Ge Research Center for Probiotics, China Agricultural University, Beijing, China
Hebei Engineering Research Center of Animal Product, Sanhe, China

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Chaodong Wu Department of Nutrition, Texas A&M University, College Station, Texas, USA

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Liang Zhao Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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. Previous studies indicated that hepatic infiltration of macrophages is the major cause of inflammatory responses in the pathology of NASH ( Mridha et al . 2017 ). In terms of decreasing NASN-related inflammation, acetate, propionate, or butyrate inhibited

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Gregory S Y Ong Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
Department of General Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

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Timothy J Cole Department of Biochemistry, Monash University, Clayton, Victoria, Australia

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Gregory H Tesch Department of Medicine, Monash University, Clayton, Victoria, Australia
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia

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James Morgan Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia

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Jennifer K Dowling Hudson Institute of Medical Research, Clayton, Victoria, Australia
Royal College of Surgeons in Ireland, Dublin, Ireland

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Ashley Mansell Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia

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Peter J Fuller Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia

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Morag J Young Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia

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inhibition of epithelial MR and associated adverse effects ( Tesch & Young 2017 ). Specifically, we identified monocyte-macrophages as a key cell type in which MR regulates pro-inflammatory cytokine release, ECM degradation and exacerbation of cardiac

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Jun Huang Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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Rita Sharma Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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Sohana Siyar Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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Vishva Sharma Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Vishwajeet Puri Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Kevin Y Lee Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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, insulin, and growth hormone ( Lee et al. 2019 ). Adipocyte hypertrophy, the primary driver of fat expansion during the development of obesity, is positively associated with adipose tissue macrophage (ATM) infiltration in visceral fat ( Weisberg et al

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André S D Molgat Chronic Disease Program, Ottawa Hospital Research Institute; and Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6

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AnneMarie Gagnon Chronic Disease Program, Ottawa Hospital Research Institute; and Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6

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Charlie Foster Chronic Disease Program, Ottawa Hospital Research Institute; and Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6

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Alexander Sorisky Chronic Disease Program, Ottawa Hospital Research Institute; and Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6

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. In addition to preadipocytes and adipocytes, adipose tissue contains macrophages (adipose tissue macrophages; ATMs). Their numbers and activation states vary with the extent of adiposity ( Weisberg et al . 2003 , Xu et al . 2003 , Lumeng et al

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Florencia Figueroa Laboratorio de Biología de la Reproducción, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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Gisela Mendoza Laboratorio de Biología de la Reproducción, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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Darío Cardozo Laboratorio de Biología de la Reproducción, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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Fabián Mohamed Area Morfología, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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Liliana Oliveros Laboratorio de Biología de la Reproducción, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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Myriam Forneris Laboratorio de Biología de la Reproducción, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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and follicular development ( Aguado 2002 ). The sympathetic nervous system enters the spleen by periarteriolar pathways and terminates in T-cell and macrophage areas ( Straub 2004 ). In addition to the presence of adrenergic receptors in these

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