Trefoil factor family member 2 (Tff2) KO mice are protected from high-fat diet-induced obesity


  • Disclosure: The present article has been approved by all listed authors and there is no conflict of interest that would prejudice its impartiality.

  • Author's contributions: MRDG collected, analyzed and interpreted the data, and drafted the manuscript. MY, IR, OM and RGC contributed to the collection, analysis and interpretation of the data. AAS and NB worked to the generation of Tff2 KO mice and critically revised the manuscript. DR contributed to design the study, specifically carcass energy analyses and in situ hybridization procedures, and critically revised the manuscript. MY and JStA conceived the study, designed it and critically revised the manuscript. JStA gave the final approval of the version to be published.

  • Funding agencies: This work was supported by the Heart and Stroke Foundation of Canada (HSFC) and the Canadian Institutes of Health Research (CIHR). Dr. St-Amand is a senior investigator supported by Fonds de la Recherche en Santé du Québec (FRSQ).

Correspondence: Jonny St-Amand (



Trefoil factor family member 2 (Tff2) is a small gut peptide, mainly known for its protective and healing functions. As previously demonstrated, high-fat (HF) feeding can rapidly and specifically modulate Tff2 transcription in key tissues of mice, including the duodenum and mesenteric adipose tissue, therefore suggesting a novel role for this gene in energy balance.

Design and Methods

To explore whether and how Tff2 can influence feeding behavior and energy metabolism, Tff2 knock-out (KO) mice were challenged with HF diet for 12 weeks, hence food and energy intakes, body composition, as well as energy excretion and serum lipid and hormonal levels were analyzed. Finally, energy efficiency was estimated.


Tff2 KO mice showed a greater appetite and higher energy intake compared to wild-type (WT). Consistently, they presented lower levels of serum leptin, and increased transcription of agouti-related protein (Agrp) in the hypothalamus. Though energy and triglyceride fecal excretion were augmented in Tff2 KO mice, digestible energy intake was superior. However, KO mice were finally protected from HF diet-induced obesity, and accumulated less weight and fat depots than WT animals, while keeping a normal lean mass. Energy efficiency was lower in HF-KO mice, while energy expenditure and locomotor activity were globally increased.


The present work demonstrates previously unsuspected roles for Tff2 and suggests it to be a mastermind in the control of energy balance and a promising therapeutic target for obesity.