TUESDAY, Oct. 9, 2012 (MedPage Today) — High levels of the satiety hormone proneurotensin may raise the risk of obesity-related diseases, researchers found.
Increasing blood levels of proneurotensin were tied to a higher risk of diabetes, cardiovascular disease, and death, Olle Melander, MD, PhD, of Skane University Hospital in Malmo, Sweden, and colleagues reported in the Oct. 10 issue of the Journal of the American Medical Association.
But the relationships were significant only for women, who also had an increased risk of breast cancer with higher levels of the hormone, the researchers wrote.
Proneurotensin is a precursor of the neurotensin hormone, a 13-amino acid peptide secreted with food intake and shown in animal models to promote satiety.
Yet little is known about its role in obesity and obesity-related disease in humans.
So Melander and colleagues measured fasting plasma levels of proneurotensin in 4,632 patients in the population-based Malmo Diet and Cancer Study at baseline between 1991 and 1994. In general, women had significantly higher levels of proneurotensin than men.
They looked at disease outcomes through January 2009, with a median follow-up ranging from 13.2 to 15.7 years depending on the disease.
Overall, they found that the risk of several obesity-related diseases rose significantly with each standard-deviation increase in proneurotensin levels.
Women also had a significantly higher risk of breast cancer with higher levels of proneurotensin, and a higher risk of total mortality, which the researchers said was driven by cardiovascular death.
Melande and colleagues noted that the interaction between gender and proneurotensin was significant only for incident cardiovascular disease, so they couldn't exclude the possibility that there's a relationship between proneurotensin levels and other adverse outcomes in men as well.
One reason the relationship may be more powerful in women is because estradiol upregulates expression of neurotensin, so women have a higher lifetime exposure to the hormone, the researchers wrote.
They also noted the seemingly paradoxical nature of the relationship between a hormone that signals fullness and an increased risk of obesity-related disease. Some might expect that high levels of the hormone would convey less overeating and subsequently less disease, they wrote, but that's not the case.
The exact explanation remains elusive, they said, but it may be that high levels of proneurotensin are a sign of neurotensin resistance.
The study was limited because it didn't correct for multiple comparisons and because it lacks a replication cohort, the researchers wrote.
Last Updated: 10/10/2012