Pseudomonas aeruginosa-derived pyocyanin reduces adipocyte differentiation, body weight, and fat mass as mechanisms contributing to septic cachexia. (August 2019)

• Record Type: Journal Article
• Authors: Larian, Nika; Ensor, Mark; Thatcher, Sean E.; English, Victoria; Morris, Andrew J.; Stromberg, Arnold; Cassis, Lisa A.
• Is Part Of: Food and chemical toxicology. Volume 130(2019)
• Page Start: 219
• Page End: 230
• Publication Date: 2019-08
• Subjects: Pyocyanin -- Pseudomonas aeruginosa -- Adipocyte -- Sepsis -- Cachexia -- Aryl hydrocarbon receptor; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.05.012
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: Pyocyanin, a bacterial virulence factor, reduces adipocyte differentiation. Pyocyanin reduces body weight and fat mass of male and female mice. Pyocyanin's mechanisms of body weight regulation are sexually dimorphic. Pyocyanin may contribute to chronic adipose cachexia associated with sepsis.