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Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients
BACKGROUND: In 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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355396/ https://www.ncbi.nlm.nih.gov/pubmed/28303483 http://dx.doi.org/10.1186/s40635-017-0128-3 |
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author | Goossens, Chloë Vander Perre, Sarah Van den Berghe, Greet Langouche, Lies |
author_facet | Goossens, Chloë Vander Perre, Sarah Van den Berghe, Greet Langouche, Lies |
author_sort | Goossens, Chloë |
collection | PubMed |
description | BACKGROUND: In 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. METHODS: We 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. RESULTS: The 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). CONCLUSIONS: Contrary 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. |
format | Online Article Text |
id | pubmed-5355396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-53553962017-03-30 Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients Goossens, Chloë Vander Perre, Sarah Van den Berghe, Greet Langouche, Lies Intensive Care Med Exp Research BACKGROUND: In 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. METHODS: We 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. RESULTS: The 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). CONCLUSIONS: Contrary 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. Springer International Publishing 2017-03-16 /pmc/articles/PMC5355396/ /pubmed/28303483 http://dx.doi.org/10.1186/s40635-017-0128-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Goossens, Chloë Vander Perre, Sarah Van den Berghe, Greet Langouche, Lies Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
title | Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
title_full | Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
title_fullStr | Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
title_full_unstemmed | Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
title_short | Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
title_sort | proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355396/ https://www.ncbi.nlm.nih.gov/pubmed/28303483 http://dx.doi.org/10.1186/s40635-017-0128-3 |
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