Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

Obesity has its epidemiological patterns continuously increasing. With controlling both diet and exercise being the main approaches to manage the energy metabolism balance, a high-fat (HF) diet is of particular importance. Indeed, lipids have a low satiety potential but a high caloric density. Thus, focusing on pharmacologically targetable pathways remains an approach with promising therapeutic potential. Within this context, trefoil factor family member 2 (Tff2) has been characterized as specifically induced by HF diet rather than low-fat diet. TFF2 has also been linked to diverse neurological mechanisms and metabolic patterns suggesting its role in energy balance. The hypothesis is that TFF2 would be a HF diet-induced signal that regulates metabolism with a focus on lipids. Within this review, we put the spotlight on key findings highlighting this line of thought. Importantly, the hypothetical mechanisms pointed highlight TFF2 as an important contributor to obesity development via increasing lipids intestinal absorption and anabolism. Therefore, an outlook for future experimental activities and evaluation of the therapeutic potential of TFF2 inhibition is given. Indeed, its knockdown or downregulation would contribute to an antiobesity phenotype. We believe this work represents an addition to our understanding of the lipidic molecular implications in obesity, which will contribute to develop therapies aiming to manage the lipidic metabolic pathways including the absorption, storage and metabolism via targeting TFF2-related pathways. We briefly discuss important relevant concepts for both basic and clinical researchers.