Editing Macrophage (section)

=== Obesity ===
It has been observed that increased number of pro-inflammatory macrophages within obese adipose tissue contributes to obesity complications including insulin resistance and diabetes type 2.<ref>Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue" ''Journal of Clinical Investigation'' 2003; 112:1796–808.</ref>

The modulation of the inflammatory state of adipose tissue macrophages has therefore been considered a possible therapeutic target to treat obesity-related diseases.<ref>{{cite journal | vauthors = Guilherme A, Henriques F, Bedard AH, Czech MP | title = Molecular pathways linking adipose innervation to insulin action in obesity and diabetes mellitus | journal = Nature Reviews. Endocrinology | volume = 15 | issue = 4 | pages = 207–225 | date = April 2019 | pmid = 30733616 | pmc = 7073451 | doi = 10.1038/s41574-019-0165-y }}</ref> Although adipose tissue macrophages are subject to anti-inflammatory homeostatic control by sympathetic innervation, experiments using [[Beta-2 adrenergic receptor|ADRB2 gene]] knockout mice indicate that this effect is indirectly exerted through the modulation of adipocyte function, and not through direct [[Beta-2 adrenergic receptor]] activation, suggesting that adrenergic stimulation of macrophages may be insufficient to impact adipose tissue inflammation or function in obesity.<ref>{{cite journal | vauthors = Petkevicius K, Bidault G, Virtue S, Newland SA, Dale M, Dugourd A, Saez-Rodriguez J, Mallat Z, Vidal-Puig A | title = Macrophage beta2-adrenergic receptor is dispensable for the adipose tissue inflammation and function | journal = Molecular Metabolism | volume = 48 | pages = 101220 | date = June 2021 | pmid = 33774223 | pmc = 8086137 | doi = 10.1016/j.molmet.2021.101220 | doi-access = free }}</ref>

Within the fat ([[Adipose tissue|adipose]]) tissue of [[CCR2]] deficient [[Mouse|mice]], there is an increased number of [[eosinophil]]s, greater alternative macrophage activation, and a propensity towards type 2 [[cytokine]] expression. Furthermore, this effect was exaggerated when the mice became [[Obesity|obese]] from a high fat diet.<ref>{{cite journal | vauthors = Bolus WR, Gutierrez DA, Kennedy AJ, Anderson-Baucum EK, Hasty AH | title = CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue | journal = Journal of Leukocyte Biology | volume = 98 | issue = 4 | pages = 467–477 | date = October 2015 | pmid = 25934927 | pmc = 4763864 | doi = 10.1189/jlb.3HI0115-018R }}</ref> This is partially caused by a phenotype switch of macrophages induced by [[necrosis]] of fat cells ([[adipocyte]]s). In an obese individual some adipocytes burst and undergo necrotic death, which causes the residential M2 macrophages to switch to M1 phenotype. This is one of the causes of a low-grade systemic chronic inflammatory state associated with obesity.<ref>{{cite journal | vauthors = Boutens L, Stienstra R | title = Adipose tissue macrophages: going off track during obesity | journal = Diabetologia | volume = 59 | issue = 5 | pages = 879–894 | date = May 2016 | pmid = 26940592 | pmc = 4826424 | doi = 10.1007/s00125-016-3904-9 }}</ref><ref>{{cite journal | vauthors = Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS | title = Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans | journal = Journal of Lipid Research | volume = 46 | issue = 11 | pages = 2347–2355 | date = November 2005 | pmid = 16150820 | doi = 10.1194/jlr.M500294-JLR200 | doi-access = free }}</ref>