Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism

Bujak, Maro; Tartaro Bujak, Ivana; Sobočanec, Sandra; Mihalj, Martina; Novak, Sanja; Ćosić, Anita; Tolušić Levak, Maja; Kopačin, Vjekoslav; Mihaljević, Branka; Balog, Tihomir; Drenjančević, Ines; Baus Lončar, Mirela (2018) Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism. Cellular physiology and biochemistry, 47 (2). pp. 827-841. ISSN 1015-8987

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Abstract

Background/Aims: Tff3 protein plays a well recognized role in the protection of gastrointestinal mucosa. The role of Tff3 in the metabolism is a new aspect of its function. Tff3 is one of the most affected liver genes in early diabetes and fatty liver rodent models. The aim of this study was to investigate the effect of Tff3 deficiency on lipid and carbohydrate metabolism and on markers of oxidative stress that accompanies metabolic deregulation. Methods: Specific markers of health status were determined in sera of Tff3 deficient mice, including glucose level, functional glucose and insulin tolerance. Composition of fatty acids (FAs) was determined in liver and blood serum by using gas chromatography. Oxidative stress parameters were determined: lipid peroxidation level via determination of lipid hydroperoxide and thiobarbituric acid reactive substances (TBARS), antioxidative capacity (FRAP) and specific antioxidative enzyme activity. The expression of several genes and proteins related to the metabolism of lipids, carbohydrates and oxidative stress (CAT, GPx1, SOD2, PPARα, PPARγ, PPARδ, HNF4α and SIRT1) was determined. Results: Tff3 deficient mice showed better glucose utilization in the glucose and insulin test. Liver lipid metabolism is affected and increased formation of small lipid vesicles is noticed. Formation of lipid droplets is not accompanied by increased liver oxidative stress, although expression/activity of monitored enzymes is deregulated when compared with wild type mice. Tff3 deficient mice exhibit reduced expression of metabolism relevant SIRT1 and PPARγ genes. Conclusion: Tff3 deficiency affects the profile and accumulation of FAs in the liver, with no obvious oxidative stress increase, although expression/activity of monitored enzymes is changed as well as the level of SIRT1 and PPARγ protein. Considering the strong downregulation of liver Tff3 in diabetic/obese mice, presence in circulation and regulation by food/insulin, Tff3 is an interesting novel candidate in metabolism relevant conditions.

Item Type:

Article

Uncontrolled Keywords:

Tff3 deficient mice; metabolism; fatty acids profile; oxidative stress

Subjects:

BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences

Divisions:

Division of Materials Chemistry

Projects:

Project title	Project leader	Project code	Project type
Sirtuin3 kao posrednik mitohondrijske funkcije u estrogen-ovisnoj otpornosti na oksidativni stres i prehranu s visokim udjelom masti-SuMERA	Tihomir Balog	IP-2014-09-4533	HRZZ
poremećena vazorelaksacija i endotelno-leukocitna interakcija (ELI) u razvoju aterosklerotskih lezija-V-ELI Athero	Ines Drenjančević	IP-2014-09-6380	HRZZ

Depositing User:

Sandra Sobočanec

Date Deposited:

15 Jun 2018 13:24

URI:

http://fulir.irb.hr/id/eprint/4086

DOI:

10.1159/000490039