Inflammation and Insulin Sensitivity in The Liver of Fructose-fed Mif Deficient Mice
2019
Аутори:
Gligorovska, LjupkaTeofilović, Ana
Veličković, Nataša
Vojnović-Milutinović, Danijela
Kovačević, Sanja
Matić, Gordana
Đorđević, Ana
Остала ауторства
Saksida, TamaraStanisavljević, Suzana
Miljković, Đorđe
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2019 by the Institute for Biological Research “Siniša Stanković”, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт:
Introduction: The macrophage migration inhibitory factor (MIF) is a key pro-inflammatory mediator involved in the regulation of energy metabolism and metabolic inflammation in the liver. Fructose overconsumption has been previously associated with development of low-grade inflammation characterized by elevated production of pro-inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) signaling pathway. The inflammatory response can disrupt insulin signaling and genetic deletion of Mif may contribute to the development of systemic insulin resistance, as well. The aim: The aim of the present study was to elucidate combined effects of Mif deficiency and fructose-enriched diet on metabolic inflammation and insulin sensitivity in the liver of male mice. Methods: Wild type (WT) and Mif deficient (MIF−/−) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on indicators of insulin sensitivity and markers of metabolic inflammation (tumor necrosis factor α (TNFα), interleukin (IL)-1β and IL-6). Deregulation of Akt signaling pathway was used as hallmark of hepatic insulin resistance. Also, the protein levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase 1 (JNK) and p38 were analyzed. Results: Mif deficient animals exibited elevated expression of IL-1β and IL-6 in the liver, regardless of the diet regime, while hepatic TNFα was unchanged in all animals. On the other hand, both total and phosphorylated ERK and JNK protein levels were decreased in all fructose-fed mice. In the same animals, impaired hepatic insulin signaling, revealed by decreased pAkt and total Akt protein levels, was observed. Conclusion: Although, Mif deficiency led to upregulation of pro-inflammatory cytokines, fructose diet did not aggravate this effect. On the other hand, insulin signalling was diminished by fructose feding independently of Mif deficiency.
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Финансирање / 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:
- Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia. Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia; 2019. p. 53.