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

AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.

Identification of the principal transcriptional regulators for low-fat and high-fat meal responsive genes in small intestine.

BACKGROUND: High-fat (HF) diet is a well-known cause of obesity. To identify principle transcriptional regulators that could be therapeutic targets of obesity, we investigated transcriptomic modulation in the duodenal mucosa following low-fat (LF) and HF meal ingestion. METHODS: Whereas one group of mice was sacrificed after fasting, the others were fed ad libitum with LF or HF meal, and sacrificed 30 min, 1 h and 3 h after the beginning of the meal. A transcriptome analysis of the duodenal mucosa of the 7 groups was conducted using both microarray and serial analysis of gene expression (SAGE) method followed by an Ingenuity Pathways Analysis (IPA). RESULTS: SAGE and microarray showed that the modulation of a total of 896 transcripts in the duodenal mucosa after LF and/or HF meal, compared to the fasting condition. The IPA identified lipid metabolism, molecular transport, and small molecule biochemistry as top three molecular and cellular functions for the HF-responsive, HF-specific, HF-delay, and LF-HF different genes. Moreover, the top transcriptional regulator for the HF-responsive and HF-specific genes was peroxisome proliferator-activated receptor alpha (PPARα). On the other hand, the LF-responsive and LF-specific genes were related to carbohydrate metabolism, cellular function and maintenance, and cell death/cellular growth and proliferation, and the top transcriptional regulators were forkhead box protein O1 (FOXO1) and cAMP response element binding protein 1 (CREB1), respectively. CONCLUSIONS: These results will help to understand the molecular mechanisms of intestinal response after LF and HF ingestions, and contribute to identify therapeutic targets for obesity and obesity-related diseases.