Objective. Adipose tissue (AT) macrophages are increased in obesity and associated with low grade inflammation. We aimed to characterize the phenotype of AT macrophages in humans in relation to obesity and insulin resistance. Design. Gene-expression levels of general macrophage markers (CD68 and CD14), proinflammatory markers/M1 (TNF-α, MCP-1, and IL-6), and anti-inflammatory markers/M2 (CD163, CD206, and IL-10) were determined by RT-PCR in subcutaneous AT samples from lean and obese subjects. Insulin resistance was determined by HOMA-IR. Results. All the macrophage markers were elevated in the AT from obese compared to lean subjects (P < 0.001). To determine the phenotype of the macrophages the level of CD14 was used to adjust the total number of macrophages. The relative expression of CD163 and IL-10 was elevated, and TNF-α and IL-6 were reduced in AT from obese subjects (all P < 0.05). In a multivariate regression analysis CD163 was the only macrophage marker significantly associated with HOMA-IR (β: 0.57; P < 0.05). Conclusion. Obesity is associated with elevated numbers of macrophages in the AT. Unexpectedly, the macrophages change phenotype by obesity, with a preponderance of M2 and a decrement of M1 markers in AT from obese subjects. Moreover, CD163 was the only macrophage marker associated with HOMA-IR after multiple adjustments.

Objective: Soluble CD163 (sCD163) is a new macrophage-specific serum marker elevated in inflammatory conditions. sCD163 is elevated in obesity and found to be a strong predictor of the development of type 2 diabetes. We investigated whether dietary intervention and moderate exercise was related to changes in sCD163 and how sCD163 is associated to insulin resistance in obesity. Design and Methods: Ninety-six obese subjects were enrolled: 62 followed a very low energy diet (VLED) program for 8 weeks followed by 3-4 weeks of weight stabilization, 20 followed a moderate exercise program for 12 weeks, and 14 were included without any intervention. Fasting blood samples and anthropometric measures were taken at baseline and after intervention. Thirty-six lean subjects were included in a control group. Results: sCD163 was significantly higher in obese subjects (2.3 6 1.0 mg/l) compared with lean (1.6 6 0.4 mg/l, P < 0.001). Weight loss (11%) induced by VLED resulted in a reduction and partial normalization of sCD163 to 2.0 6 0.9 mg/l (P < 0.001). Exercise for 12 weeks had no effect on sCD163. At baseline, sCD163 was significantly correlated with BMI (r ¼ 0.46), waist circumference (r ¼ 0.40), insulin resistance measured by the homeostasis model assessment (HOMA-IR; r ¼ 0.41; all P < 0.001), and the leptin-to-adiponectin ratio (r ¼ 0.28, P < 0.05). In a multivariate linear regression analysis with various inflammatory markers, sCD163 (b ¼ 0.25), adiponectin (b ¼ À0.24), and high sensitivity C-reactive protein (hs-CRP; b ¼ 0.20) remained independently and significantly associated to HOMA-IR (all P < 0.05). After further adjustment for waist circumference, only sCD163 was associated with HOMA-IR (P < 0.05). Conclusion: The macrophage-specific serum marker sCD163 is increased in obesity and partially normalized by dietary-induced weight loss but not by moderate exercise. Furthermore, we confirm that sCD163 is a good marker for obesity-related insulin resistance.

Throughout the Western world obesity prevalence is steadily increasing, and associated metabolic co-morbidities are projected to rise during the years to come. As weight loss and weight maintenance remains a major problem, new strategies to protect against obesity-related morbidity are needed. There is a clear association between obesity, low-grade inflammation and obesity-associated diseases, thus, the development of new anti-inflammatory substances is urgently needed as these may ultimately pave the way for novel treatments of obesity and lifestyle-related diseases. A candidate molecule is the polyphenolic compound resveratrol, and in the present review, we provide an overview of the field, and discuss the future scientific perspectives. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

BackgroundThe expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc dyshomeostasis is common in obese individuals. In the liver, zinc influx transporter ZIP14, affects proliferation and glucose metabolism but the role of ZIP14 in adipose tissue is still unknown. This study investigates ZIP14 gene expression in human adipose tissue before and after weight loss as well as the regulation of ZIP14 during early adipogenesis.MethodsFourteen obese individuals were investigated before and after a 10 week weight loss intervention and compared to 14 non-obese controls. Gene expressions of ZIP14 and peroxisome proliferator-activated receptor γ (PPARγ) were measured in subcutaneous adipose tissue and correlated with metabolic and inflammatory markers. Further, we investigated gene expression of ZIP14 and PPARγ during early adipogenesis of 3T3-L1 pre-adipocytes, together with an in silico analysis of PPARγ binding motifs in the promoter sequence of ZIP14.ResultsZIP14 was down-regulated in obese individuals compared to non-obese controls (p = 0.0007) and was up-regulated after weight loss (p = 0.0005). Several metabolic markers of clinical importance, including body mass index, triglyceride, and insulin resistance, were inversely correlated with ZIP14. During early adipogensis an up-regulation of ZIP14 gene expression was found. PPARγ gene expression was positively correlated with the ZIP14 gene expression in both adipose tissue and during adipogenesis. However, in silico analysis revealed that the ZIP14 promoter does not contain PPARγ-binding motifs.ConclusionsWe hypothesize that ZIP14-mediated zinc influx might directly influence PPARγ activity and that ZIP14 may regulate expansion and function of adipose tissue and serve as a potential biomarker for metabolic stress.Electronic supplementary materialThe online version of this article (doi:10.1186/s40608-015-0076-y) contains supplementary material, which is available to authorized users.

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