Abstract
Critical illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during illness. To investigate whether adipose tissue could protectively respond to critical illness by storing potentially toxic metabolites, such as excess circulating glucose and triglycerides. We studied adipose tissue morphology and metabolic activity markers in postmortem biopsies of 61 critically ill patients and 20 matched control subjects. Adipose morphology was also studied in in vivo biopsies of 27 patients and in a rabbit model of critical illness (n = 22). Adipose tissue from critically ill patients revealed a higher number and a smaller size of adipocytes and increased preadipocyte marker levels as compared with control subjects. Virtually all adipose biopsies from critically ill patients displayed positive macrophage staining. The animal model demonstrated similar changes. Glucose transporter levels and glucose content were increased. Glucokinase expression was up-regulated, whereas glycogen and glucose-6-phosphate levels were low. Acetyl CoA carboxylase protein and fatty acid synthase activity were increased. Hormone-sensitive lipase activity was not altered, whereas lipoprotein lipase activity was increased. A substantially increased AMP-activated protein kinase activity may play a crucial role. Postmortem adipose tissue biopsies from critically ill patients displayed a larger number of small adipocytes in response to critical illness, revealing an increased ability to take up circulating glucose and triglycerides. Similar morphologic changes were present in vivo. Such changes may render adipose tissue biologically active as a functional storage depot for potentially toxic metabolites, thereby contributing to survival.
Highlights
Supported by the Fund for Scientific Research, Flanders, Belgium (FWO), by the Research Council of the Katholieke Universiteit Leuven, and by long-term structural funding–Methusalem funding by the Flemish Government
We stained sections of adipose tissue for the macrophage marker, CD68 (Figure 1D). In both subcutaneous adipose tissue and omental adipose tissue biopsies of healthy control subjects, twothirds stained negative, whereas, in one-third of the biopsies, some positive staining was present. This was in sharp contrast with the postmortem biopsies from critically ill patients, where 100% and 95% stained positive for CD68
Our data suggest that adipose tissue is substantially altered during critical illness, with an increased number of newly formed adipocytes and macrophage infiltration
Summary
Supported by the Fund for Scientific Research, Flanders, Belgium (FWO), by the Research Council of the Katholieke Universiteit Leuven, and by long-term structural funding–Methusalem funding by the Flemish Government. Adipose tissue is substantially altered during critical illness, with an increased number of newly formed adipocytes, and is infiltrated by macrophages These adipocytes have an increased ability to store glucose and triglycerides, possibly reducing detrimental effects of high levels of these circulating metabolites. We hypothesized that adipose tissue can respond to illness by increasing its storage properties for such circulating toxic metabolites, whereby it may enhance the chances of survival To test this hypothesis, we obtained abdominal subcutaneous and omental adipose tissue biopsies from 61 nonsurviving critically ill patients with a BMI ranging from 16.3 to 31.2 kg/m2, and compared these with biopsies from 20 matched control subjects undergoing elective abdominal surgery. We studied adipose tissue morphological changes in response to critical illness in in vivo subcutaneous limb adipose tissue from 27 critically ill patients, and in the controlled setting of an animal model
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