title: Trefoil Factor 3 (TFF3) Is Regulated by Food Intake, Improves Glucose Tolerance and Induces Mucinous Metaplasia.
abstract: 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.
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ge
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Jonitha
authors.initials: J
authors.lastname: Gardner
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Rulifson
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Amgen, Protein Technologies, South San Francisco, California, United States of America.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Amgen, Protein Technologies, South San Francisco, California, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Belouski
authors.affiliation: Amgen, Protein Technologies, South San Francisco, California, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Cao
authors.affiliation: Amgen, Protein Technologies, South San Francisco, California, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Amgen, Lead Discovery, Thousand Oaks, California, United States of America.
authors.forename: Ki Jeong
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Amgen, Pathology, South San Francisco, California, United States of America.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Coberly
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Xinle
authors.initials: X
authors.lastname: Wu
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Jamila
authors.initials: J
authors.lastname: Gupte
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Miao
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Natalie
authors.initials: N
authors.lastname: Nguyen
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Bei
authors.initials: B
authors.lastname: Shan
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Yeh
authors.affiliation: Amgen, Metabolic Disorders, Thousand Oaks, California, United States of America.
authors.forename: Murielle M
authors.initials: MM
authors.lastname: Véniant
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Amgen, Metabolic Disorders, South San Francisco, California, United States of America.
authors.forename: Helene
authors.initials: H
authors.lastname: Baribault
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D000229:Dependovirus / Q000235:genetics; D059305:Diet, High-Fat; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D004435:Eating / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D007583:Jejunum / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000097:blood; D008297:Male; D008679:Metaplasia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009077:Mucins / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D009077:Mucins; D011994:Recombinant Proteins; C000604007:TFF2 protein, human; C493263:Tff3 protein, mouse; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014280:Triglycerides; D002784:Cholesterol