FrontiersinImmunologyFrontiers in Immunology Research Series: The Immunomodulatory Roles of Adipocytes

Obesity is increasing in epidemic proportions worldwide. A low-grade inflammation caused by obesity leads to its many inflammation-associated complications, including insulin resistance and type 2 diabetes, heart failure, cancer, and Alzheimer’s disease. This systemic inflammation is due to profound inflammatory changes in the adipose tissue microenvironment, at the heart of which is the adipocyte.

This cell has long been considered as a storage depot for excess energy. In the late 1990s, the adipocyte was recognized as a key endocrine cell, secreting hormones and cytokines, targeting cells throughout the body. Over 50 factors have been identified that are produced and secreted by the adipocyte. High fat diet and obesity markedly impacts production of nearly all of these proinflammatory factors. In 2013, it was discovered that the adipocyte can present antigen, similar to dendritic cells and macrophages, to activate CD4+ T effector cells. Thus, in obesity, the adipocyte exerts immunomodulatory functions, using multiple novel mechanisms to regulate inflammation. The goal of this International Review Series was to define the immune functions of the adipocyte, focusing on novel mechanisms by which the adipocyte promotes inflammation and damages target organs in obesity. A greater understanding of how the adipocyte assumes the role of an immune cell in obesity is critical to decreasing adipose tissue inflammation to fight the obesity epidemic. Drs. Willa Hsueh and David Bradley of the OSU Diabetes and Metabolism Research Center and Dr. Amin Xu, Division of Endocrinology, University of Hong Kong, served as invited Editors for this series.

Adipocytes, Innate Immunity and Obesity: A Mini-Review

Alecia Blaszczak, Anahita Jalilvand, Willa Hsueh, Diabetes and Metabolism Research Center, The Ohio State University

This review highlights the adipocyte as a source of critical metabolic hormones like leptin and adiponectin, secreting numerous factors and lipid mediators by classical endocrine mechanisms and by exosomes. The factors regulate innate immunity by targeting innate immune cells (neutrophils, macrophages, and innate lymphoid cells type 2).

Adipocyte Ceramides – The Nexus of Inflammation and Metabolic Disease

Bhagirath Chaurasia, University of Iowa, and Chad Lamar Talbot and Scott A. Summers, University of Utah

This article discusses how excessive accumulation of ceramides leads to issues of adipose tissue inflammation and dysfunction, which both underlie cardiometabolic disease. Additionally, ceramides’ role in the link between inflammation and key features of the metabolic syndrome is reviewed.

Adipose Extracellular Vesicles in Intercellular and Inter-Organ Crosstalk in Metabolic Health and Diseases

Zhe Huang and Aimin Xu, University of Hong Kong

This article provides an up-to-date overview of Adipose-derived extracellular vesicles (ADEVs) and their pathophysiological functions in relation to the regulation of immune responses, whole-body insulin sensitivity, and metabolism. Also, the authors review recent clinical evidence supporting the function of ADEVs as a contributor to obesity-related inflammation and metabolic complications.

The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease

Kaitlin Kiernan and Nancie J. MacIver, Duke University School of Medicine

This review article examines the role leptin has in influencing immune cell function, including modulating inflammation, which is ultimately crucial for determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes.

Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality

Chi-Ho Lee, David T. W. Lui, and Karen S. L. Lam, University of Hong Kong

In the pathogenesis of cardiovascular disease, inflammation plays an important role. The relationship between adipocyte fatty acid-binding protein (AFABP) and CVD and mortality, through its impact on inflammation, are examined in this review.

Adipocytes Are the Control Tower That Manages Adipose Tissue Immunity by Regulating Lipid Metabolism

Jeu Park, Jee Hyung Sohn, Sang Mun Han, Yoon Jeong Park, Jin Young Huh, Sung Sik Choe, and Jae Bum Kim, Seoul National University

This article discusses how adipocytes communicate with adipose immune cells by using lipid metabolites, as well as the recently discovered roles of adipose stem cells in the regulation of adipose tissue immunity.

The Adipocyte and Adaptive Immunity

Jianfeng Song and Tuo Deng, Second Xiangya Hospital of Central South University

Adipocytes possess an immunological role and impact how T cells and B cells participate in adaptive immunity. This article examines this relationship, as well as the role of these three cell types in the pathogenesis of various diseases.

Adipocyte Oncostatin receptor regulates adipose tissue homeostasis and inflammation

David Sanchez-Infantes, Universidad Rey Juan Carlos, and Jacqueline M. Stephens, Louisiana University

This review summarizes the role of oncostatin M receptor (OSMRβ), a proinflammatory cytokine, as a modulator of adipocyte development and function.

Clusterin and its Role in Insulin Resistance and the Cardiometabolic Syndrome

Jennifer Wittwer and David Bradley, The Ohio State University

This mini-review summarizes both the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism. Potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease is also discussed.

Interaction of Adipocyte Metabolic and Immune Functions through TBK1

Peng Zhao and Alan R. Saltiel, University of California San Diego

This review focuses on the regulation and functions of TBK1, which plays important roles in the regulation of both metabolism and inflammation in adipose tissue. Additionally, the potential of a TBK1/IKKε inhibitor as a new therapy for metabolic diseases is discussed.