Upregulation of inflammasome activity and increased gut permeability are associated with obesity in children and adolescents

Autor: Cristian Ricci, Mara Biasin, Mario Clerici, Irma Saulle, Veronica Rainone, Nasser M. Al-Daghri, Daria Trabattoni, Gian Vincenzo Zuccotti, Laura Schneider, Elisa Giani
Rok vydání: 2016
Předmět:
Male
Transcriptional Activation
0301 basic medicine
Pediatric Obesity
Adolescent
Intra-Abdominal Fat
Inflammasomes
Endocrinology
Diabetes and Metabolism
Medicine (miscellaneous)
Real-Time Polymerase Chain Reaction
digestive system
Intestinal absorption
03 medical and health sciences
Intestinal mucosa
Downregulation and upregulation
Diabetes mellitus
Humans
Medicine
Longitudinal Studies
Intestinal Mucosa
Child
Adipogenesis
Nutrition and Dietetics
business.industry
Macrophages
digestive
oral
and skin physiology
Inflammasome
medicine.disease
Obesity
Up-Regulation
Cross-Sectional Studies
030104 developmental biology
Diabetes Mellitus
Type 2
Gene Expression Regulation
Intestinal Absorption
Italy
Cardiovascular Diseases
Immunology
Female
Carrier Proteins
business
Signal Transduction
medicine.drug
Zdroj: International Journal of Obesity. 40:1026-1033
ISSN: 1476-5497
0307-0565
DOI: 10.1038/ijo.2016.26
Popis: Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity.The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age-matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro-inflammatory cytokines (interleukin (IL)-1β and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects.Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-γ, IL-12β, IL-1β, CCL2, CCL5, IL-6 and TNFα) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1β and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months.In children and adolescents, obesity is characterized by the activation of the inflammasome and by an alteration of gut permeability. Successful lifestyle modification is effective in reducing inflammation, suggesting that inhibition of the inflammasome may be a potential therapeutic strategy in obesity.
Databáze: OpenAIRE
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