Absence of CC Chemokine Ligand 2 Does Not Limit Obesity-Associated Infiltration of Macrophages Into Adipose Tissue

Inouye, Karen; Shi, Hang; Howard, Jane K.; Daly, Christine M.; Lord, Graham M.; Rollins, Barrett J.; Flier, Jeffrey S.

doi:10.2337/db07-0425

Cited by 217 publications

(177 citation statements)

References 44 publications

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“…2, A and B, and supplemental Fig. 1), and this is consistent with previous studies (25). The increase in ATM content in the epididymal fat pad was comparable with accumulation of ATMs in other visceral depots such as mesenteric and retroperitoneal fat.…”

Section: Resultssupporting

confidence: 80%

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Lü

Nguyen

et al. 2010

Journal of Biological Chemistry

217

178

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Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet-induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker. We assessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-target tissues, including muscle, liver, and adipose tissue, after the diet switch. In adipose tissue the CD11c-positive macrophages remain constant in number despite the presence of insulin sensitivity, but these macrophages now assume a new phenotype in which they no longer exhibit increased inflammatory pathway markers. Adipose tissue markers of apoptosis and necrosis were elevated on HFD and remain high after the HFD 3 NC diet switch. Furthermore, ATM accumulation preceded detectable adipocyte necrosis at the early phase of HFD. Together, these results indicate that 1) CD11c-positive M1-like ATMs can exhibit phenotypic plasticity and that the polarization of these cells between inflammatory and non-inflammatory states is well correlated to the presence of absence of insulin resistance, and 2) adipocyte necrosis and apoptosis can be dissociated from ATM accumulation.

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Section: Resultssupporting

confidence: 80%

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Lü

Nguyen

et al. 2010

Journal of Biological Chemistry

217

178

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“…The lack of correlation between macrophage infiltration and expression of the inflammatory cytokines in gWAT at week 35 remains to be explained. However, it is compatible with other results showing that the absence of MCP-1 does not limit the recruitment of macrophages to gWAT, 52 and the lack of a correlation between macrophage content in gWAT and the levels of proinflammatory cytokines in plasma in mice fed HF diet. 19,28 In fact, the previous study 19 in mice fed HF diet for 12 weeks after weaning showed similar plasma levels of TNFa, interleukin-6, interleukin-1b, MCP-1 and granulocyte-macrophage colony-stimulating factor in male and female mice, in spite of a robust sexual dimorphism in macrophage infiltration and in the expression of genes for inflammatory markers in gWAT.…”

Section: Discussionsupporting

confidence: 81%

Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control

et al. 2011

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Objective: Adverse effects of obesity on glucose homeostasis are linked to low-grade adipose tissue inflammation and accumulation of lipids in non-adipose tissues. The goal of this study was to evaluate the role of adipose tissue plasticity in a less severe deterioration of glucose homeostasis in females compared with males during the course of high-fat (HF) feeding in mice. Design: Mice of the C57BL/6N strain were fed either a chow or obesogenic HF diet for up to 35 weeks after weaning. Metabolic markers and hormones in plasma, glucose homeostasis, adipocyte size and inflammatory status of gonadal (gWAT) and subcutaneous (scWAT) adipose depots and liver steatosis were evaluated at 15 and 35 weeks of HF feeding. Results: HF-fed males were heavier than females until week B20, after which the body weights stabilized at a similar level (55-58 g) in both sexes. Greater weight gain and fat accumulation in females were associated with larger adipocytes in gWAT and scWAT at week 35. Although adipose tissue macrophage infiltration was in general less frequent in scWAT, it was reduced in both fat depots of female as compared with male mice; however, the expression of inflammatory markers in gWAT was similar in both sexes at week 35. In females, later onset of the impairment of glucose homeostasis and better insulin sensitivity were associated with higher plasma levels of adiponectin (weeks 0, 15 and 35) and reduced hepatosteatosis (weeks 15 and 35). Conclusions: Compared with males, female mice demonstrate increased capacity for adipocyte enlargement in response to a long-term HF feeding, which is associated with reduced adipose tissue macrophage infiltration and lower fat deposition in the liver, and with better insulin sensitivity. Our data suggest that adipose tissue expandability linked to adiponectin secretion might have a role in the sex differences observed in obesity-associated metabolic disorders.

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“…Coincidently, Inouye and co-workers showed that CCL2-deficient mice exhibited increased HFD-induced weight gain and comparable macrophage recruitment capabilities to control mice. CCL2-deficient mice also displayed impaired glucose tolerance, and in fact presented increased plasma glucose and reduced adiponectin levels compared with control mice (96) . These studies suggest that infiltrating macrophages are not solely pro-inflammatory and indicate that factors independent of CCR2/CCL2 are involved in macrophage recruitment.…”

Section: Obesity-induced Adipose Tissue Macrophage Recruitmentmentioning

confidence: 99%

“…Lack of CCR2 reduced HFDinduced obesity, while plasma CCL2 levels decreased exponentially with pharmacological-induced weight reduction in DIO mice (51,93) . A number of studies have disputed the involvement of the CCR2/MCP-1 axis in obesity and IR (93,96) . Abrogating CCR2 in DIO mice did not alter body weight, glucose homoeostasis or ATM infiltration (93) .…”

Section: Obesity-induced Adipose Tissue Macrophage Recruitmentmentioning

confidence: 99%

Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

et al. 2012

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High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

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Absence of CC Chemokine Ligand 2 Does Not Limit Obesity-Associated Infiltration of Macrophages Into Adipose Tissue

Cited by 217 publications

References 44 publications

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control

Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

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