Worldwide, more than 1.7 billion people are overweight, with a body mass index (BMI) higher than 25, or obese (BMI higher than 30). Additionally, more than 2.5 million deaths are attributed to the consequences of obesity each year.

Previous research has shown that neurotensin (NT) can also stimulate the growth of various cancers and increased fasting levels of pro-NT (an NT precursor hormone) are associated with development of cardiovascular disease and breast cancer. However, a role for NT as a causative factor in these diseases is unknown. NT, a 13 amino acid peptide produced mainly in the gastrointestinal tract and central nervous system, is released with fat ingestion and facilitates fatty acid absorption in the intestine The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively).

The study further used animal models to show that a deficiency in NT protects against obesity, insulin resistance and fatty liver disease associated with high fat consumption, thus identifying NT as a potential early marker of future obesity and a novel therapeutic target for this disease.

They further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin).

Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation.

The new Nature study also examined data from the Malmö Diet and Cancer Study, a population-based, prospective epidemiologic cohort of 28,449 men and women who were followed for an average of 16.5±1.5 years. The analysis showed that obese and insulin-resistant subjects have significantly elevated levels of fasting pro-NT, and the risk of developing obesity was doubled in non-obese subjects who had fasting pro-NT at the highest concentrations compared to subjects with the lowest concentrations.

These findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.

Additionally, because NT can contribute to the growth of certain cancers and is now linked with obesity, author speculates that increased NT may contribute to the higher incidence of certain cancers associated with obesity. Building on the findings from this study, future research at the University of Kentucky will examine this possible link.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17662.html