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Alternative macrophage activation and the regulation of metabolism.

Webb P - F1000 Biol Rep (2009)

Bottom Line: Macrophages are white blood cells that have important roles in phagocytosis and immune responses.A series of recent papers reveals that nuclear receptors influence the precise pathway of macrophage phenotype polarization and that these effects protect against insulin resistance and metabolic syndrome, the most important group of diseases facing the industrialized world.

View Article: PubMed Central - PubMed

Affiliation: Methodist Hospital Research Institute, Center for Diabetes Research 6565 Fannin Street, F8-045, Houston, TX 77030 USA. pwebb@tmhs.org

ABSTRACT
Macrophages are white blood cells that have important roles in phagocytosis and immune responses. A series of recent papers reveals that nuclear receptors influence the precise pathway of macrophage phenotype polarization and that these effects protect against insulin resistance and metabolic syndrome, the most important group of diseases facing the industrialized world.

No MeSH data available.


Related in: MedlinePlus

Monocytes that enter adipose tissue develop into adipose tissue macrophages (ATMs) that can be polarized in two ways: M2 macrophages respond to local Th2 cytokines to limit the inflammatory response, whereas M1 macrophages respond to local pro-inflammatory stimuli to promote local inflammatory responses and alter local adipocyte function. The peroxisome proliferator activated receptors PPARγ and PPARδ both promote M2 polarization; PPARγ plays incompletely defined roles in activation along the M2 pathway, whereas PPARδ is required for elaboration of the M2 phenotype.
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fig-001: Monocytes that enter adipose tissue develop into adipose tissue macrophages (ATMs) that can be polarized in two ways: M2 macrophages respond to local Th2 cytokines to limit the inflammatory response, whereas M1 macrophages respond to local pro-inflammatory stimuli to promote local inflammatory responses and alter local adipocyte function. The peroxisome proliferator activated receptors PPARγ and PPARδ both promote M2 polarization; PPARγ plays incompletely defined roles in activation along the M2 pathway, whereas PPARδ is required for elaboration of the M2 phenotype.

Mentions: How does disruption of the PPARγ gene in macrophages influence insulin resistance and obesity? Because M2 polarization inhibits local inflammatory responses, it seems likely that PPARγ-/- macrophages secrete inflammatory cytokines that alter adipocyte function (Figure 1). Accordingly, Odegaard and colleagues find increased expression of inflammatory markers in adipose tissue in the macrophage-specific PPARγ-knockout mice [6]. This effect is coupled to suppression of multiple genes involved in adipocyte function and insulin response, and co-culture experiments confirm that PPARγ-/- macrophages produce secreted factors that limit insulin sensitivity in adipocytes. Overall, changes in adipocyte function are likely to alter secretion of multiple adipocyte hormones that affect the systemic insulin response. In addition, reduced fat storage in adipose tissue depots will probably be coupled to increased accumulation of lipids in liver, skeletal muscle and other locations with known inhibitory effects on insulin sensitivity in these tissues. PPARγ-dependent M2 polarization might also exert direct effects on other tissues: Hevener and colleagues [12] find that hepatic insulin sensitivity varies with the extent of PPARγ-/- macrophage infiltration into liver.


Alternative macrophage activation and the regulation of metabolism.

Webb P - F1000 Biol Rep (2009)

Monocytes that enter adipose tissue develop into adipose tissue macrophages (ATMs) that can be polarized in two ways: M2 macrophages respond to local Th2 cytokines to limit the inflammatory response, whereas M1 macrophages respond to local pro-inflammatory stimuli to promote local inflammatory responses and alter local adipocyte function. The peroxisome proliferator activated receptors PPARγ and PPARδ both promote M2 polarization; PPARγ plays incompletely defined roles in activation along the M2 pathway, whereas PPARδ is required for elaboration of the M2 phenotype.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2920685&req=5

fig-001: Monocytes that enter adipose tissue develop into adipose tissue macrophages (ATMs) that can be polarized in two ways: M2 macrophages respond to local Th2 cytokines to limit the inflammatory response, whereas M1 macrophages respond to local pro-inflammatory stimuli to promote local inflammatory responses and alter local adipocyte function. The peroxisome proliferator activated receptors PPARγ and PPARδ both promote M2 polarization; PPARγ plays incompletely defined roles in activation along the M2 pathway, whereas PPARδ is required for elaboration of the M2 phenotype.
Mentions: How does disruption of the PPARγ gene in macrophages influence insulin resistance and obesity? Because M2 polarization inhibits local inflammatory responses, it seems likely that PPARγ-/- macrophages secrete inflammatory cytokines that alter adipocyte function (Figure 1). Accordingly, Odegaard and colleagues find increased expression of inflammatory markers in adipose tissue in the macrophage-specific PPARγ-knockout mice [6]. This effect is coupled to suppression of multiple genes involved in adipocyte function and insulin response, and co-culture experiments confirm that PPARγ-/- macrophages produce secreted factors that limit insulin sensitivity in adipocytes. Overall, changes in adipocyte function are likely to alter secretion of multiple adipocyte hormones that affect the systemic insulin response. In addition, reduced fat storage in adipose tissue depots will probably be coupled to increased accumulation of lipids in liver, skeletal muscle and other locations with known inhibitory effects on insulin sensitivity in these tissues. PPARγ-dependent M2 polarization might also exert direct effects on other tissues: Hevener and colleagues [12] find that hepatic insulin sensitivity varies with the extent of PPARγ-/- macrophage infiltration into liver.

Bottom Line: Macrophages are white blood cells that have important roles in phagocytosis and immune responses.A series of recent papers reveals that nuclear receptors influence the precise pathway of macrophage phenotype polarization and that these effects protect against insulin resistance and metabolic syndrome, the most important group of diseases facing the industrialized world.

View Article: PubMed Central - PubMed

Affiliation: Methodist Hospital Research Institute, Center for Diabetes Research 6565 Fannin Street, F8-045, Houston, TX 77030 USA. pwebb@tmhs.org

ABSTRACT
Macrophages are white blood cells that have important roles in phagocytosis and immune responses. A series of recent papers reveals that nuclear receptors influence the precise pathway of macrophage phenotype polarization and that these effects protect against insulin resistance and metabolic syndrome, the most important group of diseases facing the industrialized world.

No MeSH data available.


Related in: MedlinePlus