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

Abstract

Introduction: 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. Results: 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. Conclusions: 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.

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

“…Therefore TFF3 may act via multiple organs. Although TFF2 has a different distribution along the GI tract than TFF3, genetic ablation of TFF2 confers resistance to diet-induced obesity [34] corroborating the role of TFF family peptides interact in metabolic regulation.…”

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

“…4,5,31,41,104) by binding to a plethora of transmembrane glycoproteins, such as receptors, e.g., CXCR4 (40,41), integrins (42), and a CRP-Ductin/DMBT1/gp-340-like glycoprotein (42). Such transmembrane glycoproteins interacting with TFF2 (and possibly also with TFF1 and TFF3) are expected to occur particularly in the immune and central nervous systems, e.g., the body weight is regulated by hypothalamic TFF2 (139). In particular, the relatively high dissociation constants of lectin interactions explain now conclusively why relatively high TFF2 concentrations were necessary for biological activity (40,41).…”

Trefoil Factor Family Member 2 (TFF2) as an Inflammatory-Induced and Anti-Inflammatory Tissue Repair Factor

“…Tff2 has been recently characterized as a high-fat diet-induced gene in the intestinal mucosa [41] and the knock out of this gene lead to a protection from high-fat diet-induced obesity [11,42]. Both these facts could be further considered for the future exploration of the links between inflammation and metabolics.…”