BACKGROUND: Obesity is associated with insulin resistance and premature atherosclerosis. The human adipose tissue produce several adipokines including monocyte chemoattractant protein (MCP)-1, associated with cardiovascular disease and found to be involved in the pathogenesis of atherosclerosis in vitro. OBJECTIVE: (1) To compare mRNA levels of MCP-1, leptin and a macrophage-specific marker (CD68) in isolated adipocytes vs stromal-vascular (SV) cells, (2) to compare mRNA levels of MCP-1 in human adipose tissue to circulating MCP-1 and adiposity (eg BMI: kg/m 2 ) and (3) investigate the effect of weight loss in obese subjects on circulating MCP-1 and leptin. RESULTS: (1) MCP-1 and CD68 mRNA levels in isolated adipocytes vs SV cells were 17% (Po0.01) and B2% (Po0.001), respectively. Leptin mRNA levels in SV cells were B1% of that in isolated adipocytes (Po0.01). (2) MCP-1 mRNA levels correlated with circulating MCP-1 (Po0.05) and BMI (Po0.05). (3) A 12% weight loss (Po0.001) was associated with a 25% decrease in insulin levels (Po0.01). Circulating MCP-1 and leptin decreased by 20% (Po0.001) and by 24% (Po0.001), respectively. DISCUSSION: The findings demonstrate that MCP-1 is produced in isolated human adipocytes. In addition, the findings suggest that MCP-1 may be involved in obesity-related health complications and support the hypothesis that weight loss is beneficial by improving the low-grade inflammation observed in obesity.

The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk. In the EXO group the weight loss was 3.5 kg and in the DIO and DEX groups it was 12 kg in both. Vo(2max) was increased by 14-18% in the EXO and DEX groups with no changes in the DIO group. In the DIO and DEX groups, circulating levels of MCP-1, MIP-1alpha, IL-15, and IL-18 were decreased, and adiponectin was increased (P < 0.05 for all). In the EXO group, MCP-1 was decreased with 10% (P = 0.06). By combining the weight loss in all three groups, we found a correlation between the degree of weight loss and improvement in several of the inflammatory markers (P < 0.05). In AT biopsies, subjects in the DIO and DEX groups achieved a general beneficial but nonsignificant effect on the gene expression of inflammatory markers. In the EXO group, no changes in AT adipokine mRNA were found except for an increment of adiponectin (P < 0.05). In SM, the only observed change was that the gene expression of IL-6 was increased in all three groups (P < 0.05). In conclusion, rather large weight losses (>5-7%) were found to have beneficial effects on circulating inflammatory markers in these obese subjects. Aerobic exercise for 12 wk, which increased Vo(2max), was found to have no effects on circulating inflammatory markers in these obese patients. It is suggested that more intensive exercise may be necessary to affect systemic inflammation.

OBJECTIVE: Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. METHODS: Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1a-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. RESULTS: A plasma 25OHD level o50 nmol l À 1 was highly prevalent in both lean (45%) and obese (90%) women (Po0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (Po0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 were decreased by 71% (Po0.0001) and 49% (Po0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (Po0.05) after weight loss. CONCLUSION: Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss. INTRODUCTIONLow levels of circulating 25-hydroxy-vitamin D (25OHD) are associated with increased fat mass and body mass index, 1-5 but the underlying mechanism for this association is not fully elucidated. 6 Vitamin D (VD) is stored in adipose tissue (AT), and release of VD from AT is proposed to serve as an endogenous source of VD during the winter, when cutaneous production is low or absent in several parts of the world. 7 As low circulating levels of 25OHD are common in association with the obese state, 8 several studies have examined the effect of weight loss on circulating levels of 25OHD. However, results are inconsistent. After diet-and exercise-induced weight loss, both increased 9-11 and unaltered 12,13 circulating levels of 25OHD have been reported. Likewise, after major weight loss by bariatric surgery, both temporary 14-16 and long-term increases [16][17][18] in circulating levels of 25OHD have been reported, along with reports of no changes one year after surgery. 13,19 Taken together, these findings indicate that body weight is an important factor for circulating 25OHD levels. Several other explanations for the low levels of 25OHD in obesity have been proposed: a decreased exposure to sun light, 20 ...

1) Duodenal polyps are found in 4.6% of patients referred to upper endoscopy and should therefore be looked for. 2) Multiple, small polyps in the duodenal bulb are always benign and need neither biopsy nor treatment (in patients with familial polyposis biopsy is recommended). 3) In the descending duodenum polyps are rare, but a substantial number of them are adenomas. Biopsy is therefore mandatory in this localization.

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.