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


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?

SUBMITTER: Goossens C 

PROVIDER: S-EPMC6600878 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Goossens Chloë C   Goossens Chloë C   Weckx Ruben R   Derde Sarah S   Dufour Thomas T   Vander Perre Sarah S   Pauwels Lies L   Thiessen Steven E SE   Van Veldhoven Paul P PP   Van den Berghe Greet G   Langouche Lies L  

Critical care (London, England) 20190701 1


<h4>Background</h4>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.<h4>Methods</h4>In a centrally catheterized, fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we compared markers of lipolysis and f  ...[more]

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