Relationship between Innate Immune Response Toll-Like Receptor 4 (TLR-4) and the Pathophysiological Process of Obesity Cardiomyopathy

Author(s):Show less -

Pedro Henrique Rizzi Alves ^[1] ; Artur Junio Togneri Ferron ^[2] ; Mariane Róvero Costa ^[3] ; Fabiana Kurokawa Hasimoto ^[4] ; Cristina Schmitt Gregolin ; Jéssica Leite Garcia ^[6] ; Dijon Henrique Salomé de Campos ^[7] ; Antônio Carlos Cicogna ^[8] ; Letícia de Mattei ^[9] ; Fernando Moreto ^[10] ; Silméia Garcia Zanati Bazan ^[11] ; Fabiane Valentini Francisqueti-Ferron ^[12] ; Camila Renata Corrêa ^[13]

Affiliation:Show less -

^[1] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[2] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[3] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[4] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[6] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[7] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[8] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[9] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[10] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[11] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[12] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

^[13] Universidade Estadual Paulista Júlio de Mesquita Filho. Faculdade de Medicina - Brasil

• Document type: Journal article
• Source: Arquivos Brasileiros de Cardiologia; v. 117, n. 1, p. 91-99, 2021-07-26.

Abstract

Abstract Background Obesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines. Objective To test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation. Methods Male Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student’s t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant. Results The OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB. Conclusion Our findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction. (AU)

• FAPESP's process: 15/10626-0 - Interrelation of gamma-oryzanol and activation of adipose R1 and R2 adipose receptors: possible effect on improvement of obesity-associated renal function
• Grantee: Camila Renata Corrêa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/13592-1 - Analysis of gene expression of TLR4 and TNF-± in obese rats myocardial
• Grantee: Pedro Henrique Rizzi Alves
• Support Opportunities: Scholarships in Brazil - Scientific Initiation