Inflammatory mechanisms linking obesity and metabolic disease

There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.

[1]  D. Winer,et al.  Immunologic impact of the intestine in metabolic disease , 2017, The Journal of clinical investigation.

[2]  J. Flier,et al.  TLR4 links innate immunity and fatty acid-induced insulin resistance. , 2006, The Journal of clinical investigation.

[3]  G. Hotamisligil,et al.  Inflammation and metabolic disorders , 2006, Nature.

[4]  I. Verma,et al.  Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. , 2009, Cell metabolism.

[5]  Jerrold M. Olefsky,et al.  Regulation of metabolism by the innate immune system , 2016, Nature Reviews Endocrinology.

[6]  M. Birnbaum,et al.  Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. , 2007, Cell metabolism.

[7]  Y. Zick,et al.  Ser/Thr Phosphorylation of IRS Proteins: A Molecular Basis for Insulin Resistance , 2005, Science's STKE.

[8]  N. Sonenberg,et al.  Double-Stranded RNA-Dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis , 2010, Cell.

[9]  G. Hotamisligil,et al.  Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease , 2010, Cell.

[10]  P. Scherer,et al.  Adipose tissue remodeling and obesity. , 2011, The Journal of clinical investigation.

[11]  Michael Karin,et al.  A central role for JNK in obesity and insulin resistance , 2002, Nature.

[12]  Eric Vaillancourt,et al.  Coordinated Regulation of Nutrient and Inflammatory Responses by STAMP2 Is Essential for Metabolic Homeostasis , 2007, Cell.

[13]  D. Mathis.  Immunological goings-on in visceral adipose tissue. , 2013, Cell metabolism.

[14]  C. Ballantyne,et al.  Skeletal muscle inflammation and insulin resistance in obesity , 2017, The Journal of clinical investigation.

[15]  A. Hevener,et al.  IKK-beta links inflammation to obesity-induced insulin resistance. , 2005, Nature medicine.

[16]  N. Lanthier,et al.  Kupffer cell activation is a causal factor for hepatic insulin resistance. , 2010, American journal of physiology. Gastrointestinal and liver physiology.

[17]  Philipp E. Scherer,et al.  Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI , 2008, Molecular and Cellular Biology.

[18]  R. Nagai,et al.  Islet inflammation in type 2 diabetes and physiology , 2017, The Journal of clinical investigation.

[19]  J. Brüning,et al.  Hypothalamic inflammation in obesity and metabolic disease , 2017, The Journal of clinical investigation.

[20]  J. Després,et al.  Postprandial Variations of Plasma Inflammatory Markers in Abdominally Obese Men , 2006, Obesity.

[21]  P. Scherer,et al.  The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. , 2017, The Journal of clinical investigation.

[22]  L. Joosten,et al.  Inflammasome is a central player in the induction of obesity and insulin resistance , 2011, Proceedings of the National Academy of Sciences.

[23]  Y. Koyama,et al.  Liver inflammation and fibrosis. , 2017, The Journal of clinical investigation.

[24]  P. Trayhurn.  Hypoxia and adipose tissue function and dysfunction in obesity. , 2013, Physiological reviews.

[25]  Jung-whan Kim,et al.  Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation and Insulin Resistance in Obesity , 2014, Cell.

[26]  Carey N Lumeng,et al.  Inflammatory links between obesity and metabolic disease. , 2011, The Journal of clinical investigation.

[27]  J. Olefsky,et al.  LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes , 2015, Nature Medicine.

[28]  M. Scadeng,et al.  Bone marrow–specific Cap gene deletion protects against high-fat diet–induced insulin resistance , 2007, Nature Medicine.

[29]  P. Sansonetti,et al.  Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment , 2011, EMBO molecular medicine.

[30]  B. Swinburn,et al.  The global obesity pandemic: shaped by global drivers and local environments , 2011, The Lancet.

[31]  J. Olefsky,et al.  Omega 3 fatty acids and GPR120. , 2012, Cell metabolism.

[32]  C. Lumeng,et al.  The initiation of metabolic inflammation in childhood obesity , 2017, The Journal of clinical investigation.

[33]  Stephen J. Weiss,et al.  A Pericellular Collagenase Directs the 3-Dimensional Development of White Adipose Tissue , 2006, Cell.

[34]  Wei Ying,et al.  Hematopoietic-Derived Galectin-3 Causes Cellular and Systemic Insulin Resistance , 2016, Cell.

[35]  A. Saltiel,et al.  Obesity induces a phenotypic switch in adipose tissue macrophage polarization. , 2007, The Journal of clinical investigation.

[36]  H. Ginsberg,et al.  C-C Chemokine Receptor 2 (CCR2) Regulates the Hepatic Recruitment of Myeloid Cells That Promote Obesity-Induced Hepatic Steatosis , 2010, Diabetes.

[37]  T. McLaughlin,et al.  Role of innate and adaptive immunity in obesity-associated metabolic disease , 2017, The Journal of clinical investigation.

[38]  Gökhan S Hotamisligil,et al.  Endoplasmic reticulum stress and atherosclerosis , 2010, Nature Medicine.

[39]  A. Goldfine,et al.  Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk. , 2017, The Journal of clinical investigation.

[40]  S. Summers,et al.  Sphingolipids and insulin resistance: the five Ws , 2010, Current opinion in lipidology.