Pseudomonas aeruginosa-derived pyocyanin reduces adipocyte differentiation, body weight, and fat mass as mechanisms contributing to septic cachexia

Nika Larian, Mark Ensor, Sean E. Thatcher, Victoria English, Andrew J. Morris, Arnold Stromberg, Lisa A. Cassis

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Pseudomonas aeruginosa, a leading cause of sepsis, produces pyocyanin, a blue-pigmented virulence factor. Sepsis is associated with cachexia, but mechanisms are unknown and conventional nutrition approaches are not effective treatments. Pyocyanin has affinity for the aryl hydrocarbon receptor (AhR), which is expressed on adipocytes and regulates adipocyte differentiation. The purpose of this study was to define in vitro and in vivo effects of pyocyanin on adipocyte differentiation and body weight regulation as relates to septic cachexia. In 3T3-L1 preadipocytes, pyocyanin activated AhR and its downstream marker CYP1a1, and reduced differentiation. Administration of pyocyanin to male C57BL/6J mice acutely reduced body temperature with altered locomotion, but caused sustained weight loss. Chronic pyocyanin administration to male and female C57BL/6J mice resulted in sustained reductions in body weight and fat mass, with adipose-specific AhR activation. Pyocyanin-treated male mice had decreased energy expenditure and physical activity, and increased adipose explant lipolysis. In females, pyocyanin caused robust reductions in body weight, adipose-specific AhR activation, and increased expression of inflammatory cytokines in differentiated adipocytes. These results demonstrate that pyocyanin reduces adipocyte differentiation and decreases body weight and fat mass in male and female mice, suggesting that pyocyanin may play a role in septic cachexia.

Original languageEnglish
Pages (from-to)219-230
Number of pages12
JournalFood and Chemical Toxicology
Volume130
DOIs
StatePublished - Aug 2019

Bibliographical note

Funding Information:
Research reported was supported by grant P42ES007380 (LAC, AM, AS) from the National Institute of Environmental Health Sciences (NIEHS) within the National Institutes of Health (NIH). We also acknowledge NIH T32DK007778 for trainee support (NL). Indirect calorimetry and body lean and fat mass were quantified through research support cores within NIH P30 GM127211 (LAC).

Funding Information:
Research reported was supported by grant P42ES007380 (LAC, AM, AS) from the National Institute of Environmental Health Sciences (NIEHS) within the National Institutes of Health (NIH). We also acknowledge NIH T32DK007778 for trainee support (NL). Indirect calorimetry and body lean and fat mass were quantified through research support cores within NIH P30 GM127211 (LAC).

Publisher Copyright:
© 2019

Keywords

  • Adipocyte
  • Aryl hydrocarbon receptor
  • Cachexia
  • Pseudomonas aeruginosa
  • Pyocyanin
  • Sepsis

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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