Obesity and Type 2 Diabetes mellitus induce lipopolysaccharide tolerance in rat neutrophils

Author(s)

Tatagiba Kuwabara, Wilson Mitsuo ^[1] ; Fukusawa Yokota, Caroline Naomi ^[1] ; Curi, Rui ^{[1, 2]} ; Alba-Loureiro, Tatiana Carolina ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Cruzeiro Sul, Interdisciplinar Hlth Sci Postgrad Program, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, DEC 3 2018.
• Web of Science Citations: 1

Abstract

Obesity and diabetes implicate in various health complications and increased mortality caused by infection. Innate immune system is broadly affected by these diseases, leading the patients to an immunosuppressive state. A mechanism that leads innate immune cells to a less capacity of killing microorganism is the impaired TLR4 activation. TLR4 recognizes a component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS), and when activated increases the production of inflammatory substances. Neutrophils are components of the innate immune system and are the first responders to an invading agent. The correct activation of TLR4 in these cells is required for the initiation of the inflammatory process and elimination of the microorganisms. The aim of this study was to evaluate the influence of type 2 diabetes and obesity in the TLR4 pathway in rat neutrophils. Two experimental models were used: Goto-Kakizaki rats and high-fat-diet induced obese Wistar rats. To evaluate neutrophil response to LPS, intratracheal LPS instillation was used. Neutrophils from obese and diabetic animals exhibited tolerance to LPS, mainly by the impaired production of cytokines and chemokines and the low content of phospho-NF kappa B and phospho-IKB alpha. Neutrophils from both experimental models had increased cell death, impaired in vivo migration and myeloperoxidase activity. (AU)

• FAPESP's process: 16/15766-7 - Hypertrophy Skeletal muscle in STZ diabetic rats.
• Grantee: Rui Curi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise
• Grantee: Rui Curi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/03175-1 - The role of neutrophils in the inflammatory response during type 2 Diabetes mellitus: cellular and molecular mechanisms
• Grantee: Tatiana Carolina Alba Loureiro
• Support Opportunities: Regular Research Grants