Doença hepática gordurosa associada à disfunção metabólica em ratos resistentes à obesidade

• Ano de defesa: 2023
• Autor(a) principal: Madureira, Amanda Rangel
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Nutrição e Saúde; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Nutrição e Saúde
• Palavras-chave em Português: Dieta hiperlipídica; Resistência à obesidade; Resistência insulínica; DHGAM; Tecido adiposo; subject.br-rjbn; Nutrição
• Link de acesso: http://repositorio.ufes.br/handle/10/16670

Introduction: Obesity is a chronic disease of complex etiology and represents one of the main metabolic risk factors for the development of metabolic dysfunction associated fatty liver disease (MAFLD). Interestingly, there is a class of individuals with a capacity for lower mass gain and body fat deposition when ingesting high-calorie diets, classified as to obesity- resistant (OR). However, the mechanisms involved in the relationship between AT inflammation and hepatic fat deposition in OR animals are unclear. Studies evaluating DHGAM in ROb dietary model are scarce. Objective: To investigate the presence of fatty liver disease associated with metabolic dysfunction, as well metabolic parameters and morphological aspects of adipose tissues in obesity-resistant rats fed a high-fat diet (HFD). Methods: 71 Wistar rats, 30 days old, were submitted to an obesity induction protocol and exposure to an HFD, covering 4 weeks of induction and 10 weeks of exposure, totaling 14 consecutive weeks. Rats were initially randomized into two groups: a) DP: fed a standard diet (n = 35) and b) DH: fed a high-fat diet (n = 36). Subsequently, after applying the tercile classification criterion, the animals were redistributed into three groups: a) control (C, n=12), fed a standard diet; b) obese (Ob, n=12), and c) resistant to obesity (OR, n=12), both fed a HFD. The evolution of the animals' body mass, adiposity, feeding behavior, biochemical and hormonal characteristics, morphology of hepatic and adipose tissues, and protein quantification of hepatic pIRS-1 by western blotting were analyzed. Comparison of experimental groups was performed by one-way or two-way ANOVA, complemented with Bonferroni or Tukey multiple comparisons test for parametric data and Kruskal-Wallis for non-parametric data complemented with Dunn's test, as appropriate. The significance level considered for all variables was 5%. Results: At the end of the experimental protocol, the animals in the OR group showed intermediate values in relation to the other groups in the variables final body mass, sum of fat deposits, serum leptin and total liver mass, being statistically lower than the Ob group and higher than group C. Biochemical analyzes of total cholesterol and HDL, as well as glycemic and insulin profiles, did not differ between OR and Ob groups, being greater than group C. Histological evaluations of TA showed that ROb group had adipocyte area similar to the Ob group and lower number of fat cells. Morphological and pathophysiological analysis of the liver showed DHGAM present at an early stage in the OR group and at a more advanced stage in the Ob group, with a diagnosis of NASH. The protein quantification of hepatic pIRS-1 did not show statistical differences between the groups, but in the descriptive statistics it showed an increase, in relation to C, of 114% and 138% in the Ob and OR groups, respectively. Discussion: The results of the present study denote metabolic disruption in adipose and hepatic tissues of OR animals in a similar way to Ob. Accepting the hypothesis postulated here, the data indicate that OR animals present the same metabolic risks associated with obesity and development when consuming DH chronically. Conclusion: it is concluded that the chronic consumption of saturated HFD causes changes in metabolic tissues, as well as the development of fatty liver disease associated with metabolic dysfunction concomitantly with insulin resistance, regardless of the presence of obesity.