Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones

Autor: Chloë Goossens, Ruben Weckx, Sarah Derde, Thomas Dufour, Sarah Vander Perre, Lies Pauwels, Steven E. Thiessen, Paul P. Van Veldhoven, Greet Van den Berghe, Lies Langouche
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Critical Care, Vol 23, Iss 1, Pp 1-17 (2019)
Druh dokumentu: article
ISSN: 1364-8535
DOI: 10.1186/s13054-019-2506-6
Popis: Abstract Background ICU-acquired weakness is a debilitating consequence of prolonged critical illness that is associated with poor outcome. Recently, premorbid obesity has been shown to protect against such illness-induced muscle wasting and weakness. Here, we hypothesized that this protection was due to increased lipid and ketone availability. Methods In a centrally catheterized, fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we compared markers of lipolysis and fatty acid oxidation in lean and obese septic mice (n = 117). Next, we compared markers of muscle wasting and weakness in septic obese wild-type and adipose tissue-specific ATGL knockout (AAKO) mice (n = 73), in lean septic mice receiving either intravenous infusion of lipids or standard parenteral nutrition (PN) (n = 70), and in lean septic mice receiving standard PN supplemented with either the ketone body 3-hydroxybutyrate or isocaloric glucose (n = 49). Results Obese septic mice had more pronounced lipolysis (p ≤ 0.05), peripheral fatty acid oxidation (p ≤ 0.05), and ketogenesis (p ≤ 0.05) than lean mice. Blocking lipolysis in obese septic mice caused severely reduced muscle mass (32% loss vs. 15% in wild-type, p
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