Obesity is associated with macrophage accumulation in adipose tissue

Weisberg, Stuart P.; McCann, Daniel; Desai, Manisha; Rosenbaum, Michael; Leibel, Rudolph L.; Ferrante, Anthony W.

doi:10.1172/jci19246

Cited by 5,111 publications

(5,453 citation statements)

References 98 publications

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“…In this sense, white blood cell counts (Dixon and O'Brien 2006;Vozarova et al 2002) as well as plasma levels of acute-phase proteins (Gómez-Ambrosi et al 2006;Yudkin et al 1999) and pro-inflammatory cytokines (Catalán et al 2007a;Lasselin et al 2014) are elevated in obese and T2D patients experimenting a reduction after weight loss (Bastard et al 2000;Catalán et al 2011). The obesity-associated low-grade inflammation results in the persistent stimulation of the immune system mainly characterized by the infiltration of adipose tissue with macrophages (Poulain-Godefroy et al 2008;Weisberg et al 2003) and the activation of circulating immune cells shifting toward a pro-inflammatory profile (Ghanim et al 2004;Lumeng et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and osteopontin

et al. 2015

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Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro-or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P \ 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P \ 0.0001) and osteopontin (P \ 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P \ 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P \ 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are manifest in PBMC, which might contribute to the low-grade chronic inflammation that characterizes obesity.

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Section: Introductionmentioning

confidence: 99%

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and osteopontin

et al. 2015

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“…In mouse models of obesity and in obese humans, macrophages infiltrate visceral and subcutaneous adipose tissue and surround dead or dying adipocytes, forming characteristic crown-like structures (CLS) [84,86,90,91]. WAT inflammation is defined by the presence of these inflammatory foci.…”

Section: Inflammation: the Emerging Link Between Obesity And Cancermentioning

confidence: 99%

Obesity and Cancer: Concepts and Challenges

Argolo

Iyengar

Hudis

2015

Indian J Surg Oncol

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The rates of overweight and obesity are increasing worldwide in both developed and developing countries. Obesity is a major public health problem as it is associated with many diseases, including diabetes, hypertension, dyslipidemia, atherosclerosis, and some types of cancer. Breast cancer is a malignancy in which both the risk of development and the prognosis are negatively impacted by the obese state. The precise mechanisms pathophysiologically linking obesity and cancer are still under investigation. The biological basis for these associations includes both systemic and local tissue effects and white adipose tissue inflammation appears to be a critical component. A comprehensive understanding of the mechanisms linking obesity, inflammation and cancer may provide an opportunity for the development of strategies to attenuate the negative impact of obesity.

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“…First of all, it is not clear whether resistin can be considered to be an adipokine as most reports now agree that resistin is expressed in mononuclear cells and not adipocytes (8,9). Although, in obesity, adipose tissue is infiltrated by macrophages and may as such secrete resistin (10,11). Reports linking the protein to obesity and type 2 diabetes have also been conflicting (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

“…Although resistin is predominantly expressed in adipocytes in mice, its expression in humans is most abundant in mononuclear cells/macrophages (8,9). In obesity, it has been shown that macrophages infiltrate the adipose tissue (10,11) and this could therefore explain the reports of resistin expression in adipose tissue. Furthermore, serum levels of obese humans were found to be higher than those in lean control subjects (12,13).…”

Section: Introductionmentioning

confidence: 99%

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

Beckers

Freitas²,

Zegers³

et al. 2011

European Journal of Endocrinology

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Objective: In this study, we hypothesized that mutations in the resistin encoding gene, RETN, may cause a monogenic form of obesity. Design/methods: We screened the coding region of RETN in 81 morbidly obese adults, 263 overweight and obese children/adolescents, and 116 healthy lean subjects. In vitro experiments include qPCR, ELISA, and western blot for WT and mutant resistin transfected into 3T3-L1 adipocytes. Results: Mutation analysis identified five sequence variants in our patient populations:0 -UTR C100 A/G, T73T, IV3-61 C/A, and C78S. In our control population, we only found the 3 0 -UTR C87 G/A variant. We started functional experiments for the C78S mutation that was found in a 20-year-old obese male (body mass index (BMI)Z39.7 kg/m 2 ) and his obese mother (BMIZ31.9 kg/m 2 ). In vitro testing demonstrated that the mutation does not impair mRNA expression. We identified a 100-fold lower extracellular protein concentration for mutant resistin compared with WT levels using a resistin ELISA on cell culture medium (PZ4.87!10 K6 ). We also detected a decreased intracellular concentration for the mutant protein (tenfold lower relative levels, PZ0.007). The plasma resistin levels of the proband and his mother, however, did not differ significantly from lean control individuals. Conclusions: In conclusion, we identified the first missense mutation in resistin in a morbidly obese proband and his obese mother. Functional testing of the mutant protein suggests that the C78S mutant protein is degraded, possibly resulting in a decreased extracellular concentration, which may predispose to obesity. 164 927-936 European Journal of Endocrinology

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Obesity is associated with macrophage accumulation in adipose tissue

Cited by 5,111 publications

References 98 publications

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and osteopontin

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and osteopontin

Obesity and Cancer: Concepts and Challenges

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

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