Plasma Proneurotensin and Incidence of Diabetes, Cardiovascular Disease, Breast Cancer, and Mortality

Abstract

Fasting proneurotensin was significantly associated with the development of diabetes, cardiovascular disease, breast cancer, and with total and cardiovascular mortality.

Biomarkers in ACS and Heart Failure: Should Men and Women Be Interpreted Differently?

“…PNT is a stable precursor to neurotensin, a hormone that has been linked to satiety and obesity, and a receptor for PNT is a major human CAD susceptibility gene variant. A large population-based study demonstrated that PNT concentrations were significantly higher in women and predicted the onset of diabetes mellitus, CV disease including coronary events and stroke, breast cancer, and death; however, this relationship was observed only in women (48 ). Though the mechanisms for these relationships and their clinical implications are not entirely clear, these initial epidemiological results suggest that PNT may be useful for identifying women at high overall CV risk in the absence of traditional risk factors.…”

An obligatory role for neurotensin in high-fat-diet-induced obesity

“…Neurotensin (NT), a 13-amino acid peptide predominantly localized in specialized enteroendocrine (EE) cells of the small bowel 4 and released by fat ingestion 5 , facilitates fatty acid (FA) translocation in rat intestine 6 , and stimulates growth of various cancers 7 ; the effects of NT are mediated through three known NT receptors (NTR1, 2 and 3) 8 . Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality 9 ; however, a role for NT as a causative factor in these diseases is unknown. Here, we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption.…”

“…Fasting plasma concentrations of pro-NT were analyzed from 4,632 middle-aged subjects of the population-based Malmö Diet and Cancer Study Cardiovascular Cohort 9 (Extended Data Table 1). The age- and sex-adjusted likelihood of being obese, abdominally obese and insulin resistant significantly increased across quartiles of pro-NT plasma levels (p = 0.01, 0.001 and <0.0001, respectively, Table 1).…”

Validation of Plasma Proneurotensin as a Novel Biomarker for the Prediction of Incident Breast Cancer

“…Thus, we recently tested whether fasting plasma concentration of a stable 117-amino acid fragment from the N-terminal part of the prepro-neurotensin/neuromedin precursor hormone, referred to as proneurotensin, which is produced in stoichiometric amounts relative to the mature neurotensin, predicts the development of breast cancer during long-term follow-up in the Malm€ o Diet and Cancer Study (MDCS), a population-based prospective cohort study from Southern Sweden. We found that there was a strong and graded positive relationship between fasting plasma concentration of proneurotensin and later development of breast cancer with the top versus the bottom quartile of proneurotensin having an approximately 2.4-fold increased risk (14). Here, we attempted to replicate the finding in an independent cohort of women from the Malm€ o Preventive Project (MPP).…”

“…Between 1974 and 1992, a total of 33,346 men and women of the homogenous ethnic background from the Malm€ o city area were recruited and screened for traditional risk factors of all-cause mortality and cardiovascular disease (CVD). A detailed description of baseline procedures may be found elsewhere (15,16) , and (iii) did not participate in the MDCS discovery study (14). Of these 1,500 women, fasting plasma samples for measurement of proneurotensin were available in 1,439.…”