Synergistic Modulation of Inflammatory but not Metabolic Effects of High‐Fat Feeding by CCR2 and CX3CR1

Zhang, Hanrui; Hinkle, Christine; O’Neill, Sean M.; Shi, Jianting; Caughey, Jennifer; Lynch, Emma; Lynch, Gina; Gerelus, Mark; Tsai, Andrew S. D.; Shah, Rachana; Ferguson, Jane F.; Ahima, Rexford S.

doi:10.1002/oby.21900

Cited by 8 publications

(12 citation statements)

References 41 publications

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“…There is evidence that accumulation of ATMs contributes to obesity-induced insulin resistance (13,14). For example, deletion of chemokine (C-C motif) ligand 2 (CCL2) reduces ATM accumulation and improves insulin sensitivity in some but not all cases (5,6,15,16), while overexpression of CCL2 promotes insulin resistance (7). Moreover, chemical or genetic disruption of macrophages or their functions improves insulin sensitivity (17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

Hill

Lim

Kim

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

306

302

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Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.

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mentioning

confidence: 99%

Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

Hill

Lim

Kim

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

306

302

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“…HFD-induced obesity is typically associated with increased recruitment of macrophages from the blood monocyte niche to EWAT and, albeit to less extent, SAT ( 21 ). To test whether observed SAT macrophage accumulation upon aHFD challenge is a consequence of increased monocyte recruitment, we analyzed SAT macrophages for the expression of CCR2, a chemokine receptor expressed on macrophages originating from classical monocytes ( 22 – 25 ). We noted no difference in CCR2 + macrophage subsets between the groups, but the CCR2 − CD206 + macrophage subset significantly expanded upon aHFD ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

Vujičić,

Broderick,

Salmantabar

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages’ engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.

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“…Immune cell phenotypes were evaluated in 18 studies using flow cytometry or immunohistochemistry 42,46,49,53,68–81 (Table 2). Most studies evaluated AT sites, 46,49,53,68–76,78–81 blood/plasma, 42,74,76,78 and spleen 42,69,73,77 …”

Section: Resultsmentioning

confidence: 99%

Sex differences in systemic inflammation and immune function in diet‐induced obesity rodent models: A systematic review

Braga Tibaes,

Barreto Silva,

Wollin

et al. 2023

Obesity Reviews

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SummaryUnderstanding sex differences in immunological responses in the context of obesity is important to improve health outcomes. This systematic review aimed to investigate sex differences in systemic inflammation, immune cell phenotype, and function in diet‐induced obesity (DIO) animal models. A systematic search in Medline, Embase, and CINAHL from inception to April 2023 was conducted, using a combination of the following concepts: sex, obesity, cytokines, and immune cell phenotypes/function. Forty‐one publications reporting on systemic inflammation (61%), cell phenotype (44%), and/or function (7%) were included. Females had lower systemic inflammation compared with males in response to DIO intervention and a higher proportion of macrophage (M)2‐like cells compared with males that had a higher proportion of M1‐like in adipose tissue. Although there were no clear sex differences in immune function, high‐fat DIO intervention remains an important factor in the development of immune dysfunction in both males and females, including disturbances in cytokine production, proliferation, and migration of immune cells. Yet, the mechanistic links between diet and obesity on such immune dysfunction remain unclear. Future studies should investigate the role of diet and obesity in the functionality of immune cells and employ adequate methods for a high‐quality investigation of sex differences in this context.

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Synergistic Modulation of Inflammatory but not Metabolic Effects of High‐Fat Feeding by CCR2 and CX3CR1

Cited by 8 publications

References 41 publications

Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

Sex differences in systemic inflammation and immune function in diet‐induced obesity rodent models: A systematic review

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