Trefoil Factor 3 (TFF3) Is Regulated by Food Intake,Improves Glucose Tolerance and Induces Mucinous Metaplasia |
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| Authors: | Hongfei Ge Jonitha Gardner Xiaosu Wu Ingrid Rulifson Jinghong Wang Yumei Xiong Jingjing Ye Edward Belouski Ping Cao Jie Tang Ki Jeong Lee Suzanne Coberly Xinle Wu Jamila Gupte Lynn Miao Li Yang Natalie Nguyen Bei Shan Wen-Chen Yeh Murielle M Véniant Yang Li Helene Baribault |
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| Institution: | 1. Amgen, Metabolic Disorders, South San Francisco, California, United States of America.; 2. Amgen, Metabolic Disorders, Thousand Oaks, California, United States of America.; 3. Amgen, Protein Technologies, South San Francisco, California, United States of America.; 4. Amgen, Lead Discovery, Thousand Oaks, California, United States of America.; 5. Amgen, Pathology, South San Francisco, California, United States of America.; Johns Hopkins University School of Medicine, UNITED STATES, |
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| 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. |
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