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...imal rates of thermogenesis, but such extremes of O2 utilization would not occur with white fat (49, 50, 189). Capillary density is lower in adipose tissue of obese humans compared with lean subjects =-=(144, 185)-=-, and this is the case in both visceral and subcutaneous depots (137). Interestingly, while in lean humans the density is greater in the visceral fat than the subcutaneous, there is no difference betw...

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...). As we observed a higher number of small-sized adipocytes together with higher levels of Pref-1, our results could be interpreted as increased adipogenesis. The high number of CD68 positive–stained cells in all studied adipose tissue biopsies of critically ill patients, obtained from both the subcutaneous and the omental site, postmortem and in vivo, is striking. CD68 is recognized to be a specific macrophage marker (28). Macrophage accumulation in adipose tissue has been demonstrated in obesity (29, 30), and systemic hypoxia has been associated with increased inflammation in adipose tissue (31). Several reasons for macrophage accumulation in adipose tissue of obese people have been proposed. It has been suggested that hypertrophic or expanding adipocytes may produce chemotactic signals, leading to macrophage recruitment in an attempt to limit adipose tissue expansion (32–34). The other suggested mechanism involves oxidative stress in the endothelium due to increased glucose delivery. Endothelial injury in the adipose tissue could attract inflammatory cells, such as macrophages, further exacerbating local inflammation (35). Why critical illness is associated with increased infiltrati...

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...ring adipose expansion could feasibly lead to adipose tissue fibrosis. Indeed, genetically obese mice and obese humans show significantly reduced adipose VEGF-A accompanied by lower capillary density =-=(4, 25)-=-, suggesting reduced adaptive angiogenesis. Although hypoxia up-regulates VEGF-A, the protective angiogenic response observed in 11HSD1/ mice did not follow the canonical hypoxia-HIF-dependent path...

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..., triggering thesexpression of hypoxia-inducible factor-1 and inflammatory genes [62]. Similarly, oxygenspartial pressure in subcutaneous adipose tissue negatively correlates with adiposity inshumans =-=[63]-=-. Thus, hypoxia could be a trigger for adipose tissue inflammation.s11sFigure 2. Immune cell infiltration of adipose tissue in obesitysLean individuals have higher M2/M1 macrophage, TH2/TH1 T cell and...

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... and increased oxygen tension within the adipose tissue (AT) have been suggested to contribute to AT dysfunction and inflammation, which may subsequently increase the risk for metabolic complications =-=(9, 10, 23, 37)-=-. Chronic hypoxemia in COPD, on the other hand, accelerates loss of body and fat masses, in part by increasing the resting metabolic rate (29, 33, 43). However, the effects of chronic hypoxia on AT fu...

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...s [26]. As indicated, many findings stem from experiments performed in extremely low orshigh pO2. Under in vivo pO2 levels (3%–11% O2), conflicting results were found showing positive [5] orsnegative =-=[29]-=- correlations to the inflammatory status. Additionally, concentrations of 10% O2 andsbelow increased adipocyte triacylglycerol content and enhanced secretion rates of IL-6 andsdipeptidyl-peptidase-4 [...

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... a greater proportion of small cells (Keswell et al. unpublished). ese data, together with our �ndings of negative correlation between gluteal fat mass and insulin sensitivity [14], suggest that central obesity may not be a good predictor of insulin resistance in women of African ancestry, but rather that gluteal adipocyte size may be a more sensitive indicator of insulin resistance. 7. Hypoxia Hypertrophy of adipocytes, particularly when the expanding cell mass exceeds the compensatory vascular supply, results in hypoxia in adipose tissue, with a concomitant reduction in insulin sensitivity [60, 61]. Cellular adaptation to hypoxia is accomplished through the activation of an array of oxygen sensing transcription factors, including hypoxia inducible factor-1 (HIF-1) [62], which induces the expression of proangiogenic proteins such as vascular endothelial growth factor (VEGF) and pyruvate dehydrogenase kinase-1 (PDK1) [63]. However, in obese adipose tissue, even though HIF-1 protein levels increase, VEGF does not increase [64] and is accompanied by reduced capillary density [60, 64]. Furthermore, plasminogen activator inhibitor-1 (PAI-1), 4 Journal of Obesity T 1: Ethnic differences in...

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...son, WI). Liver fat content was measured by computed tomography as previously described (17). A needle biopsy of periumbilical subcutaneous adipose tissue was performed immediately prior to the clamp =-=(19,20)-=-, to obtain �300 mg of tissue which was processed as described below. The same procedures were repeated on day 28. An additional blood sample for CRP was taken at 3 days of overfeeding. Immunohistoche...

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.... Compared with lean subjects, overweight/obese individuals appear to have 44% lower capillary density and 58% lower VEGF, suggesting that rarefaction could drive obesity via hypoxia and inflammation =-=[85]-=-. Caffeine might be a better choice for targeting the signaling cascade of angiogenesis. It was suggested to be a promising therapeutic agent with a direct impact on neovascularization of human tumors...