Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity
John M. Wentworth,Gaetano Naselli,Wendy A. Brown,Lisa Doyle,Belinda Phipson,Gordon K. Smyth,Martin Wabitsch,Paul E. O'Brien,Leonard C. Harrison +8 more
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TLDR
These findings identify proinflammatory CD11c+ ATMs as markers of insulin resistance in human obesity and indicates they metabolize lipid and may initiate adaptive immune responses.Abstract:
OBJECTIVE Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity.
RESEARCH DESIGN AND METHODS Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies.
RESULTS ATMs comprised CD11c+CD206+ cells in “crown” aggregates and solitary CD11c−CD206+ cells at adipocyte junctions. In obese women, CD11c+ ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c+ ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1β, -6, -8, and -10; tumor necrosis factor-α; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c+ ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c− ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c+ ATMs, but not CD11c− ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes.
CONCLUSIONS These findings identify proinflammatory CD11c+ ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c+ ATMs indicates they metabolize lipid and may initiate adaptive immune responses.read more
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The immune cells in adipose tissue.
TL;DR: The modulation of immune cell populations in adipose tissue is reviewed and regulatory processes implicated in controlling the interface between metabolism and immunologic function are discussed.
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CCR5 Plays a Critical Role in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Both Macrophage Recruitment and M1/M2 Status
Hironori Kitade,Kazuki Sawamoto,Mayumi Nagashimada,Hiroshi Inoue,Yasuhiko Yamamoto,Yoshimichi Sai,Toshinari Takamura,Hiroshi Yamamoto,Ken-ichi Miyamoto,Henry N. Ginsberg,Naofumi Mukaida,Shuichi Kaneko,Tsuguhito Ota +12 more
TL;DR: It is noteworthy that transplantation of Ccr5−/− bone marrow was sufficient to protect against impaired glucose tolerance and the effects of loss of CCR5 were related to both reduction of total ATM content and an M2-dominant shift in ATM polarization.
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Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity.
TL;DR: The subcutaneous adipose tissue (SAT) is the largest and best storage site for excess lipids as discussed by the authors, however, it has a limited ability to expand by recruiting and/or differentiating available precursor cells.
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Chronic adipose tissue inflammation: all immune cells on the stage
Gökhan Cildir,Gökhan Cildir,Semih Can Akıncılar,Semih Can Akıncılar,Vinay Tergaonkar,Vinay Tergaonkar +5 more
TL;DR: The fundamental roles of various immune cells in adipose tissue during the initiation and progression of obesity-induced inflammation are highlighted and potential anti-inflammatory therapies from different mechanistic points of view are discussed.
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Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function?
Michael J Kraakman,Andrew J. Murphy,Andrew J. Murphy,Karin Jandeleit-Dahm,Karin Jandeleit-Dahm,Helene L. Kammoun +5 more
TL;DR: There is emerging evidence revealing a more complex scenario with the spectrum of macrophages states exceeding well beyond the M1/M2 binary classification and confused further by human and animal models exhibiting different macrophage profiles.
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