Alterations in adipose tissue during critical illness: An adaptive and protective response?
BACKGROUND
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.


OBJECTIVE
To investigate whether adipose tissue could protectively respond to critical illness by storing potentially toxic metabolites, such as excess circulating glucose and triglycerides.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Langouche
Lies
L
Department and Laboratory of Intensive Care Medicine, Katholieke Universiteit Leuven, Belgium. lies.langouche@med.kuleuven.be
Perre
Sarah Vander
SV
Thiessen
Steven
S
Gunst
Jan
J
Hermans
Greet
G
D'Hoore
André
A
Kola
Blerina
B
Korbonits
Márta
M
Van den Berghe
Greet
G
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000222:Adaptation, Physiological; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002102:Cadaver; D016638:Critical Illness; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D064429:Fatty Acid Synthases / Q000378:metabolism; D005260:Female; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011817:Rabbits
D015415:Biomarkers; D064429:Fatty Acid Synthases; D005941:Glucokinase; C548261:LPL protein, human; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase; D005947:Glucose