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Intensive Care Medicine Experimental

, 5:16

First Online: 16 March 2017Received: 07 September 2016Accepted: 07 March 2017DOI: 10.1186-s40635-017-0128-3

Cite this article as: Goossens, C., Vander Perre, S., Van den Berghe, G. et al. ICMx 2017 5: 16. doi:10.1186-s40635-017-0128-3


BackgroundIn prolonged non-obese critically ill patients, preservation of adipose tissue is prioritized over that of the skeletal muscle and coincides with increased adipogenesis. However, we recently demonstrated that in obese critically ill mice, this priority was switched. In the obese, the use of abundantly available adipose tissue-derived energy substrates was preferred and counteracted muscle wasting. These observations suggest that different processes are ongoing in adipose tissue of lean vs. overweight-obese critically ill patients.

MethodsWe hypothesize that to preserve adipose tissue mass during critical illness, adipogenesis is increased in prolonged lean critically ill patients, but not in overweight-obese critically ill patients, who enter the ICU with excess adipose tissue. To test this, we studied markers of adipogenesis in subcutaneous and visceral biopsies of matched lean n = 24 and overweight-obese n = 24 prolonged critically ill patients. Secondly, to further unravel the underlying mechanism of critical illness-induced adipogenesis, local production of eicosanoid PPARγ agonists was explored, as well as the adipogenic potential of serum from matched lean n = 20 and overweight-obese n = 20 critically ill patients.

ResultsThe number of small adipocytes, PPARγ protein, and CEBPB expression were equally upregulated p ≤ 0.05 in subcutaneous and visceral adipose tissue biopsies of lean and overweight-obese prolonged critically ill patients. Gene expression of key enzymes involved in eicosanoid production was reduced COX1, HPGDS, LPGDS, ALOX15, all p ≤ 0.05 or unaltered COX2, ALOX5 during critical illness, irrespective of obesity. Gene expression of PLA2G2A and ALOX15B was upregulated in lean and overweight-obese patients p ≤ 0.05, whereas their end products, the PPARγ-activating metabolites 15s-HETE and 9-HODE, were not increased in the adipose tissue. In vitro, serum of lean and overweight-obese prolonged critically ill patients equally stimulated adipocyte proliferation p ≤ 0.05 and differentiation lipid accumulation, DLK1, and CEBPB expression, p ≤ 0.05.

ConclusionsContrary to what was hypothesized, adipogenesis increased independently of initial BMI in prolonged critically ill patients. Not the production of local eicosanoid PPARγ agonists but circulating adipogenic factors seem to be involved in critical illness-induced adipogenesis. Importantly, our findings suggest that abundantly available energy substrates from the adipose tissue, rather than excess adipocytes, can play a beneficial role during critical illness.

KeywordsCritical illness Obesity Adipogenesis Eicosanoids Abbreviations15dPGJ215-Deoxy-Δ-12,14-prostaglandin J2

15s-HETE15-Hydroxyeicosatetraenoic acid

9-HODE9-Hydroxyoctadecadienoic acid


ALOX15Arachidonate 15-lipoxygenase

ALOX15BArachidonate 15-lipoxygenase type B

ALOX5Arachidonate 5-lipoxygenase

ANOVAAnalysis of variance

BMIBody mass index

CEBPBCCAAT-enhancer-binding protein beta

COX1Cyclooxygenase 1

COX2Cyclooxygenase 2

DLK1Delta-like 1 homolog

FBSFetal bovine serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

hADSCsHuman adipose-derived stem cells

HPGDSHematopoietic prostaglandin D synthase

ICUIntensive care unit


LPGDSProstaglandin D2 synthase

PLA2Phospholipase A2

PLA2G2APhospholipase A2 group IIA

PPARγPeroxisome proliferator-activated receptor gamma

RNA18S5RNA, 18S ribosomal 5

RPMIRoswell Park Memorial Institute

SEMStandard error of the mean

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Autor: Chloë Goossens - Sarah Vander Perre - Greet Van den Berghe - Lies Langouche


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