The peptide neurotensin (NT) directly promotes fat absorption and obesity, suggest data from mice, fruit flies and humans published online this week in Nature. The results show that middle-aged humans with high levels of pro-NT (a stable NT precursor) have twice the risk of developing obesity later in life compared to people with low levels. NT could therefore be a potential target for obesity prevention and treatment.
Mark Evers and colleagues found that NT-deficient mice fed a high-fat diet absorb less fat than their wild-type littermates and are also protected from other conditions related to high fat intake, such as increased insulin resistance. They also show in both mice and fruit flies that NT inhibits the activity of a key enzyme (AMPK) that regulates metabolism. This pathway, the authors suggest, may have been conserved through evolution to ensure the efficient absorption of ingested fats. An analysis of 4,632 human adults involved in a longitudinal study showed that pro-NT levels were significantly associated with body mass index and waist size. Non-obese people with pro-NT levels in the highest quartile were more than twice as likely to become obese later in life as those with pro-NT levels in the lowest quartile. The authors note that further research is needed to determine whether pro-NT levels can also predict future obesity in children and adolescents.