METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE IN OBESITY-RESISTANT RATS
Name: AMANDA RANGEL MADUREIRA
Publication date: 16/03/2023
Examining board:
Name |
Role |
|---|---|
| ANA PAULA LIMA LEOPOLDO | Advisor |
Summary: Introduction: Those to obesity- resistant (OR) have less mass gain and body fat deposition
when ingesting high-calorie diets, a phenomenon observed both in humans and in experimental
animals. However, the level of metabolic risk in these OR individuals is unclear, such as the
development of fatty liver disease associated with metabolic dysfunction (MAFLD). 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 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) SD: fed a standard diet (n = 35) and b) HFD:
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) obesity- resistant (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 non-alcoholic steatohepatitis. 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 HFD chronically. Conclusion: Chronic consumption of a high-fat-diet rich in
saturated fat promotes alterations in the metabolic tissues of obesity-resistant rats, as well as
the development of fatty liver disease associated with metabolic dysfunction concomitantly
with insulin resistance.
