Energy and metabolic pathways in trefoil factor family member 2 (Tff2) KO mice beyond the protection from high-fat diet-induced obesity

Trefoil factor family member 2 (TFF2) is a small gut peptide. We have previously shown that Tff2 knock out (KO) mice are protected from high-fat (HF) diet-induced obesity (De Giorgio et al., 2013a). Thus, exploring Tff2 KO-related pathways of mice at the genomic, proteinic and biochemical levels would allow us to elucidate the processes behind this protection from obesity. To explore the metabolic and energetic effects related to Tff2 deficiency, we used sampled blood from the previous study to measure levels of free fatty acids, glucose, glycerol and triglycerides in serum. Expression levels of selected genes and proteins related to energy metabolism in the skeletal muscle, liver and adipose tissue were also studied. Following the 12-wk challenging of Tff2 KO and WT mice with both HF and low-fat diet, Tff2 KO mice had lower levels of serum glucose, triglycerides and glycerol. Importantly, western blotting and Q_RT-PCR revealed that the expression levels of selected genes and proteins are toward less fat storage and increased energy expenditure by enhancing lipid and glucose utilization via oxidative phosphorylation. We mapped a part of the metabolic and biochemical pathways of lipids and glucose involving the adipose tissue, liver, skeletal muscle and sympathetic nervous system that protect Tff2 KO mice from the HF diet-induced obesity. Our data highlight Tff2-related pathways as potential targets for obesity therapies. •Trefoil factor family member 2 (TFF2) is involved in high-fat diet-induced obesity.•Tff2 KO mice are protected from the high-fat diet-induced obesity.•We showed molecular mechanisms behind this protection.•We mapped Tff2 KO-related energetic and metabolic pathways.•Our data point Tff2-Related pathways as potential therapeutic targets for obesity