Absence of macrophage inflammatory protein-1α does not impact macrophage accumulation in adipose tissue of diet-induced obese mice

Abstract

Surmi BK, Webb CD, Ristau AC, Hasty AH. Absence of macrophage inflammatory protein-1␣ does not impact macrophage accumulation in adipose tissue of diet-induced obese mice. Am J Physiol Endocrinol Metab 299: E437-E445, 2010. First published June 15, 2010; doi:10.1152/ajpendo.00050.2010.-Macrophages and T-lymphocytes are known to accumulate in the white adipose tissue (WAT) of obese mice and humans, but the factors that cause this infiltration are not yet determined. Chemokines, which attract leukocytes to inflammatory sites, are candidates for this process. Macrophage inflammatory protein-1␣ (MIP-1␣) expression is significantly elevated in WAT of obese mice and humans and positively correlates with fasting plasma insulin, but its potential role in leukocyte recruitment to WAT is unknown. MIP-1␣-deficient, heterozygous, and wild-type mice were fed a Western diet (WD) for 16 wk. Plasma lipids, adipose tissue mass, energy expenditure, food intake, liver triglyceride content, and inflammatory cytokine expression were not different among genotypes. Gene expression of macrophage markers F4/80 and CD68, as well as T-lymphocyte marker CD3ε was increased in perigonadal WAT of obese WD-fed mice but was not influenced by MIP-1␣ expression level. Immunohistochemical analysis of WAT also showed no effect of MIP-1␣ on macrophage content. Two related chemokines, MIP-1␤ and RANTES, had reduced expression in obese male MIP-1␣-deficient mice compared with wild-type controls (P Յ 0.05). In mice fed the WD for 6 wk, WAT macrophage content was unchanged; however, CD8ϩ T-lymphocytes accumulated to a lesser extent in the MIP-1␣-null mice. Therefore, expression of MIP-1␣, as well as that of MIP-1␤ and RANTES, increases as a consequence of weight gain, but these chemokines may not be required for the recruitment of monocytes to WAT during diet-induced obesity in mice and may impact T-lymphocyte recruitment only at early time points after WD feeding. chemokine; adipose tissue macrophage; macrophage inflammatory protein-1␤; regulated upon activation, normal T cell expressed and secreted PROINFLAMMATORY MACROPHAGES AND T-LYMPHOCYTES accumulate in the white adipose tissue (WAT) of obese mice and humans (6,14,22,25,31,(33)(34)(35). Research within this field has focused on multiple topics related to adipose tissue macrophages (ATMs) and T-lymphocytes, but many questions remain unanswered. In particular, although many different genes have been show to be upregulated in obese WAT, the individual contribution of many of these factors to the recruitment of immune cells to WAT has not been determined.One group of candidates for the recruitment of inflammatory cells into WAT is the family of "chemotactic cytokines," referred to as chemokines, which induce chemotaxis of leukocytes. According to their classic definition, chemokines are small, 8-to 10-kDa proteins that share structural similarity (1, 18). Chemokines have been implicated in chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis and, recently, obesity. Many chemo...

Immunity as a link between obesity and insulin resistance

“…In agreement with these findings, Ccr2 deficient mice exhibit low ATM numbers (Weisberg et al, 2006), while PSGL-1 knockout mice are protected from high-fat diet-induced adipose inflammation (Sato et al, 2011). In contrast, MIP-1a-deficient mice are not protected against high-fat diet induced macrophage infiltration into adipose tissue (Surmi et al, 2010). Thus, while MCP-1 appears to be a key mediator of the initiation of adipose tissue inflammation in obesity, the exact mechanisms remain to be elucidated.…”

Loss of CCR5 results in glucose intolerance in diet-induced obese mice

“…Strikingly though, differences in ATM numbers, inflammation, and insulin sensitivity are not detected until after long periods of HF diet feeding despite a nearly complete absence of circulating inflammatory monocytes. Deficiency of CCL3 (MIP-1␣) was shown by our group to have no effect on ATM number (14,35). Similarly, deficiency of the fractalkine receptor CX3CR1 has no effect on ATMs or IR (23).…”

Haematopoietic leptin receptor deficiency does not affect macrophage accumulation in adipose tissue or systemic insulin sensitivity

“…Several genetic models that either disrupt macrophage recruitment to AT (Kanda, Tateya et al 2006; Weisberg, Hunter et al 2006; Odegaard, Ricardo-Gonzalez et al 2007; Surmi, Webb et al 2010) or promote an adipose tissue macrophage switch towards an “M2” or anti-inflammatory phenotype (Bouhlel, Derudas et al 2007; Odegaard, Ricardo-Gonzalez et al 2007; Westcott, Delproposto et al 2009) have been explored. Despite the great progress made in this field in the past decade, methods to actively decrease macrophage recruitment to AT or diminish their inflammatory impact on this tissue are poorly understood.…”