The intestinal factor Tff3 and a miRNA network regulate murine caloric metabolism

Shah, Aftab Ali; Leidinger, Petra; Keller, Andreas; Wendschlag, Anke; Backes, Christina; Baus-Lončar, Mirela; Meese, Eckart; Blin, Nikolaus

doi:10.4161/rna.8.1.13687

Cited by 15 publications

(15 citation statements)

References 38 publications

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“…Direct effect of Tff3 on hepatocytes was demonstrated by overexpression of Tff3 in primary mouse hepatocytes (mice fed by standard diet), which inhibited the expression of gluconeogenic genes and decreased cellular glucose output [11]. This is in line with our observation of miRNA species being used to identify glycolysis/gluoconeogenesis pathways as a possible target of Tff3 action [34]. Another study by Ge at al., also in the dietinduced obesity mouse model, showed that overexpression of Tff3 in vivo improved glucose tolerance without affecting body weight, fasting insulin, triglyceride, cholesterol and leptin levels [10].…”

Section: Cellular Physiologysupporting

confidence: 75%

Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism

Bujak

Sobočanec³

et al. 2018

Cell Physiol Biochem

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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.

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Section: Cellular Physiologysupporting

confidence: 75%

Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism

Bujak

Sobočanec³

et al. 2018

Cell Physiol Biochem

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“…In agreement with our observations, TFF3 overexpression showed no significant effect on body weight. Given our findings and those of Xue et al the observation that TFF3 knockout mice have a reduced body weight is unexpected [32]. TFF3 deficiency also weakens the defense of intestinal mucosa, raising the question of whether the published body weight loss in the TFF3-KO mice is caused by a change in energy homeostasis or is a consequence of increased sensitivity to inflammation [33].…”

Section: Discussionsupporting

confidence: 60%

Trefoil Factor 3 (TFF3) Is Regulated by Food Intake, Improves Glucose Tolerance and Induces Mucinous Metaplasia

Gardner

et al. 2015

PLoS ONE

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Trefoil factor 3 (TFF3), also called intestinal trefoil factor or Itf, is a 59 amino acid peptide found as a homodimer predominantly along the gastrointestinal tract and in serum. TFF3 expression is elevated during gastrointestinal adenoma progression and has been shown to promote mucosal wound healing. Here we show that in contrast to other trefoil factor family members, TFF1 and TFF2, TFF3 is highly expressed in mouse duodenum, jejunum and ileum and that its expression is regulated by food intake. Overexpression of TFF3 using a recombinant adeno-associated virus (AAV) vector, or daily administration of recombinant TFF3 protein in vivo improved glucose tolerance in a diet-induced obesity mouse model. Body weight, fasting insulin, triglyceride, cholesterol and leptin levels were not affected by TFF3 treatment. Induction of mucinous metaplasia was observed in mice with AAV-mediated TFF3 overexpression, however, no such adverse histological effect was seen after the administration of recombinant TFF3 protein. Altogether these results suggest that the therapeutic potential of targeting TFF3 to treat T2D may be limited.

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“…The majority of these factors have not been previously associated with the development of an anti-nematode immune response. However, PCK2 has been associated with TFF3 expression [25], CNBP has been shown to be responsive to the Th2 polarising cytokine IL4 [26] and STAT1 is well known for a general role in response to interferon gamma [27]. We also identified a group of 207 proteins that may be actively secreted into the luminal mucus.…”

Section: Discussionmentioning

confidence: 94%

Proteomic analysis of the abomasal mucosal response following infection by the nematode, Haemonchus contortus, in genetically resistant and susceptible sheep

Nagaraj

Harsha

Reverter

et al. 2012

Journal of Proteomics

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The intestinal factor Tff3 and a miRNA network regulate murine caloric metabolism

Abstract: (2011) The intestinal factor Tff3 and a miRNA network regulate murine caloric metabolism, RNA Biology, 8:1,[77][78][79][80][81]

Cited by 15 publications

References 38 publications

Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism

Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism

Trefoil Factor 3 (TFF3) Is Regulated by Food Intake, Improves Glucose Tolerance and Induces Mucinous Metaplasia

Proteomic analysis of the abomasal mucosal response following infection by the nematode, Haemonchus contortus, in genetically resistant and susceptible sheep

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