Toll‐like receptor 5 in obesity: The role of gut microbiota and adipose tissue inflammation. (22nd January 2015)

• Record Type: Journal Article
• Authors: Pekkala, Satu; Munukka, Eveliina; Kong, Lingjia; Pöllänen, Eija; Autio, Reija; Roos, Christophe; Wiklund, Petri; Fischer‐Posovszky, Pamela; Wabitsch, Martin; Alen, Markku; Huovinen, Pentti; Cheng, Sulin
• Is Part Of: Obesity. Volume 23:Number 3(2015:Mar.)
• Page Start: 581
• Page End: 590
• Publication Date: 2015-01-22
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20993
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20993-sec-0001" sec-type="section"> <title>Objective</title> <p>This study aimed at establishing bacterial flagellin‐recognizing toll‐like receptor 5 (TLR5) as a novel link between gut microbiota composition, adipose tissue inflammation, and obesity.</p> </sec> <sec id="oby20993-sec-0002" sec-type="section"> <title>Methods</title> <p>An adipose tissue microarray database was used to compare women having the highest (<italic>n</italic> = 4, H‐TLR) and lowest (<italic>n</italic> = 4, L‐TLR) expression levels of TLR5‐signaling pathway genes. Gut microbiota composition was profiled using flow cytometry and FISH. Standard laboratory techniques were used to determine anthropometric and clinical variables. <italic>In vivo</italic> results were verified using cultured human adipocytes.</p> </sec> <sec id="oby20993-sec-0003" sec-type="section"> <title>Results</title> <p>The H‐TLR group had higher flagellated <italic>Clostridium</italic> cluster XIV abundance and <italic>Firmicutes</italic>‐to‐<italic>Bacteroides</italic> ratio. H‐TLR subjects had obese phenotype characterized by greater waist circumference, fat %, and blood pressure (<italic>P</italic> < 0.05 for all). They also had higher leptin and lower adiponectin levels (<italic>P</italic> < 0.05 for both). Six hundred and sixty‐eight metabolism‐ and inflammation‐related adipose tissue genes were differentially expressed between the groups. <italic>In vitro</italic> studies confirmed that flagellin activated TLR5 inflammatory pathways, decreased insulin signaling, and increased glycerol secretion.</p> </sec> <sec id="oby20993-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The <italic>in vivo</italic> findings suggest that flagellated <italic>Clostridium</italic> cluster XIV bacteria contribute to the development of obesity through distorted adipose tissue metabolism and inflammation. The <italic>in vitro</italic> studies in adipocytes show that the underlying mechanisms of the human findings may be due to flagellin‐activated TLR5 signaling.</p> </sec> </abstract>