Modulation of hepatic lipid metabolism in obesity-resistant mice on a high-fat diet
2023
Аутори:
Vratarić, MilošTeofilović, Ana
Vojnović Milutinović, Danijela
Veličković, Nataša
Bursać, Biljana
Gligorovska, Ljupka
Mićić, Bojana
Jovanović, Mirna
Đorđević, Ana
Остала ауторства
Dubljević, ZoranaТип документа:
Конференцијски прилог (Објављена верзија)
,
© 2023 by the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт:
Introduction: High-fat diet primarily leads to obesity but it can also lead to obesity resistant (OR) phenotype
with various metabolic complications. Liver plays central role in modulating lipid metabolism in
response to dyslipidemia induced by adipose tissue hypertrophy. The aim of this study was to define key
regulatory points that adjust lipid metabolism in the liver of OR mice on high-fat diet (HFD).
Methods:Male C57BL/6J mice were divided into two groups: control group on normal diet (10 kcal% fat,
D12450J, Research Diets, USA) and HFD group (60 kcal% fat, D12492, Research Diets, USA). After 14 weeks,
mice on HFD were classified as obese or OR based on 30% difference in body weight gain compared
with controls. Liver sections were analyzed histologically, while alterations in hepatic lipid metabolism
were assessed by qPCR and Western blot.
Results: Although HFD restricted hepatic de novo lipogenesis, increased influx of free fatty acids (FFA)
led to accumulation of lipid droplets in the liver of obese mice. In OR mice, liver morphology was restored,
as was expression of insulin sensitive sterol regulatory element-binding protein 1c (SREBP-1c).
Level of FFA transporter CD36 was reduced, whereas higher expression of diacylglycerol acyltransferase
2 limited lipotoxicity in OR compared with obese mice. FFA β-oxidation remained unchanged in both
HFD groups.
Conclusion: Lower FFA input and reduced lipid storage and lipotoxicity in the liver of OR mice suggest
that dyslipidemic complications associated with obesity could be ameliorated by targeted modulation
of expression of FFA transporters and regulators of lipid droplet formation.
Кључне речи:
obesity; obesity resistance; lipid metabolism; liverФинансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Dobrijević Z, editor. Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade ; 2023. p. 147. (Trends in Molecular Biology; Special Issue).