Effects of Mif deficiency and fructose-enriched diet on lipid metabolism in the mouse liver
2019
Аутори:
Gligorovska, LjupkaTeofilović, Ana
Veličković, Nataša
Vojnović-Milutinović, Danijela
Kovačević, Sanja
Matić, Gordana
Đorđević, Ana
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2019 Malaysian Society for Biochemistry and Molecular Biology
Метаподаци
Приказ свих података о документуАпстракт:
The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in metabolic inflammation and regulation of energy metabolism in the liver. Genetic deletion of Mif may contribute to the development of systemic insulin resistance, while fructose overload can disturb hepatic lipid metabolism leading to steatosis, inflammation and type 2 diabetes. The aim of the present study was to elucidate the impact of combined effects of Mif deficiency and fructose-enriched diet on insulin sensitivity and lipid metabolism in the liver of male mice. We analysed the effects of 9-week 20 % fructose-enriched diet on indicators of systemic insulin sensitivity, liver histology and biochemical parameters of lipid metabolism in wild type and MIF deficient (MIF−/−) C57Bl/6J mice. The expression of the following lipogenic genes was examined: fatty acid synthase (Fas), acetyl-CoA carboxylase (Acc) and stearoyl-CoA desaturase-1 (Scd1). Levels of insulin-regulated transcriptional factors involved in lipogenesis (sterol regulatory element-binding protein-1c, SREBP-1c and carbohydrate-response element-binding protein, ChREBP), together with the expression of hepatic fatty acid metabolism regulator (peroxisome-proliferator-activated receptor α, PPARα) were also analysed. Mif deficiency did not affect plasma free fatty acid and triglyceride levels, but impaired systemic insulin sensitivity regardless of the diet. In MIF−/− animals, liver histological analysis confirmed the presence of lipid droplets and focal necrosis, but these effects were more pronounced in MIF−/− mice on fructose diet. Although Acc and Fas levels were unchanged, elevated levels of Scd1, SREBP-1c and ChREBP, together with decreased PPARα protein level, were most likely responsible for the lipid accumulation observed in the liver of MIF−/− animals. In conclusion, the results show that energy-rich fructose diet potentiates the effects of Mif deficiency on development of fatty liver and systemic insulin resistance.
Кључне речи:
Mif deficiency; fructose-enriched diet; liver; lipid metabolism; insulin resistanceФинансирање / пројекти:
- Улога стероидних хормона у неуроендокриној адаптацији на стрес и патофизиологији метаболичког синдрома - молекуларни механизми и клиничке импликације (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41009)
У:
- Young Scientist Program 2019. 27th FAOBMB Conference 2019, 44th Annual Conference of MSBMB, and IUBMB Special Symposium; 2019 Aug 15-18; Selangor, Malaysia. Malaysian Society for Biochemistry and Molecular Biology; 2019. p. 39.