CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

Zheng, Changwen; Yang, Qian; Xu, Chengfu; Shou, Peishun; Cao, Jiafeng; Jiang, Menghui; Chen, Qing; Cao, Gang; Han, Yanyan; Li, Fengying; Cao, Wei; Zhang, Liying; Zhang, Li; Shi, Yufang; Wang, Ying

doi:10.1073/pnas.1500396113

Cited by 83 publications

(60 citation statements)

References 63 publications

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“…In line with this, mice lacking Col6 show extreme adipocyte hypertrophy without metabolic disease . In line with this, a recent study has shown that deletion of the integrin CD11b inhibits alternative activation and proliferation of adipose tissue macrophages (McGregor et al, 2013;Zheng et al, 2015). Fibrosis is a universal response to inflammation, an attempt of wound healing that occurs in multiple tissues upon chronic inflammation.…”

Section: Extracellular Matrix and Fibrosismentioning

confidence: 84%

Adipose tissue: between the extremes

2017

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Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole-body lipid handling, serves as the body's major energy storage compartment and insulation barrier, and secretes numerous endocrine mediators such as adipokines or lipokines. As a consequence, dysfunction of these processes in adipose tissue compartments is tightly linked to severe metabolic disorders, including obesity, metabolic syndrome, lipodystrophy, and cachexia. While numerous studies have addressed causes and consequences of obesity-related adipose tissue hypertrophy and hyperplasia for health, critical pathways and mechanisms in (involuntary) adipose tissue loss as well as its systemic metabolic consequences are far less understood. In this review, we discuss the current understanding of conditions of adipose tissue wasting and review microenvironmental determinants of adipocyte (dys)function in related pathophysiologies.

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Section: Extracellular Matrix and Fibrosismentioning

confidence: 84%

Adipose tissue: between the extremes

2017

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“…In this context, it is of note that in adipose tissue macrophages, the presence of CD11b limits their proliferation and their alternative activation. 56 A further and unexpected surprise was the fact that the erythroid response in Spi-C cell numbers were provided to support this claim). 33 It was argued that heme challenge led to "local differentiation of monocytes into RPMs, thus replenishing the resident population lost by heme toxicity" 4 by adapting a phenotype that is by definition heme-vulnerable?…”

Section: Discussionmentioning

confidence: 98%

The macrophage contribution to stress erythropoiesis: when less is enough

Ulyanova

Phelps

Papayannopoulou

2016

Blood

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• Significant expansion only of native splenic macrophages that are F4/80 1 /Cd11b lo occurs in both post-Epo and post-hemolysis-induced stress.• VCAM-1 2/2 mice, like Spi-C 2/2 , mice have significantly decreased macrophages but did not have a compromised E-stress response.Although the importance of native bone marrow and spleen macrophages in enhancing baseline and stress erythropoiesis has been emphasized over several decades, their kinetic and phenotypic changes during a variety of stress responses have been unclear. Furthermore, whether monocyte-derived recruited macrophages can functionally substitute for inadequate or functionally impaired native macrophages has been controversial and seem to be not only tissue-but also stress-type dependent. To provide further insight into these issues, we made detailed observations at baseline and post-erythroid stress (E-stress) in 2 mouse models with genetically depressed macrophage numbers and compared them to their controls. We documented that, irrespective of the stressinduced (hemolytic or post-erythropoietin [Epo]) treatment, only native CD11b lo splenic macrophages expand dramatically post-stress in normal mice without significant changes in the monocyte-derived CD11b hi subset. The latter remained a minority and did not change post-stress in 2 genetic models lacking either Spi-C or VCAM-1 with impaired native macrophage proliferative expansion. Although CD11b lo macrophages in these mice were one-fifth of normal at their peak response, surprisingly, their erythroid response was not compromised and was similar to controls. Thus, despite the prior emphasis on numerical macrophage reliance to provide functional rescue from E-stress, our data highlight the importance of previously described non-macrophage-dependent pathways activated under certain stress conditions to compensate for low macrophage numbers. (Blood. 2016;128(13):1756-1765

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“…The majority of macrophages infiltrated in white adipose tissue in obesity co-express CD11b and CD11c [76]. Moreover, CD11b deficient mice are protected from development of HFD-induced insulin resistance through reduction of alterative activation and proliferation of adipose tissue macrophages [77]. CD11c-positive adipose tissue macrophages are identified as markers of insulin resistance in human obesity [78].…”

Section: Ecm Receptors In the Adipose Tissuementioning

confidence: 99%

“…These results suggest that the activation of HA-CD44 pathway regulates macrophage infiltration and inflammation in the adipose tissue of HFD-fed mice. It has been previously shown that the genetic deletion of β2 integrin CD11b protects mice from development of HFD-induced insulin resistance by suppressing the alterative activation and the proliferation of adipose tissue macrophages [77]. …”

Section: Proposed Model For How Ecm-receptor Interaction Is Linkedmentioning

confidence: 99%

Adipose extracellular matrix remodelling in obesity and insulin resistance

Lin

Chun

2016

Biochemical Pharmacology

179

130

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The extracellular matrix (ECM) of adipose tissues undergoes constant remodelling to allow adipocytes and their precursor cells to change cell shape and function in adaptation to nutritional cues. Abnormal accumulation of ECM components and their modifiers in adipose tissues has been recently demonstrated to cause obesity-associated insulin resistance, a hallmark of type 2 diabetes. Integrins and other ECM receptors (e.g. CD44) that are expressed in adipose tissues have been shown to regulate insulin sensitivity. It is well understood that a hypoxic response is observed in adipose tissue expansion during obesity progression and that hypoxic response accelerates fibrosis and inflammation in white adipose tissues. The expansion of adipose tissues should require angiogenesis; however, the excess deposition of ECM limits the angiogenic response of white adipose tissues in obesity. While recent studies have focused on the metabolic consequences and the mechanisms of adipose tissue expansion and remodelling, little attention has been paid to the role played by the interaction between peri-adipocyte ECM and their cognate cell surface receptors. This review will address what is currently known about the roles played by adipose ECM, their modifiers, and ECM receptors in obesity and insulin resistance. Understanding how excess ECM deposition in the adipose tissue deteriorates insulin sensitivity would provide us hints to develop a new therapeutic strategy for the treatment of insulin resistance and type 2 diabetes.

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CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

Cited by 83 publications

References 63 publications

Adipose tissue: between the extremes

Adipose tissue: between the extremes

The macrophage contribution to stress erythropoiesis: when less is enough

Adipose extracellular matrix remodelling in obesity and insulin resistance

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