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Greater plasma pro-NT levels identify NAFLD in adults

Stephen Padilla
14 Jun 2018

Increased levels of plasma proneurotensin (pro-NT) can predict the presence or severity of nonalcoholic fatty liver disease (NAFLD) in adults, a recent study has shown. Moreover, NT may specifically promote hepatic fat accumulation in dysmetabolic individuals through mechanisms possibly related to increased insulin resistance.

Plasma pro-NT was significantly higher in obese individuals with biopsy-proven NAFLD (53 percent) than in those without NAFLD (183.6±81.4 vs 86.7±56.8 pmol/L; p<0.001). Higher pro-NT was associated with NAFLD presence (p<0.001) and severity (p<0.001), age, female sex, insulin resistance, and type 2 diabetes (T2D). [J Clin Endocrinol Metab 2018;103:2253-2260]

Greater pro-NT identified NAFLD with an area under receiver operating characteristic curve of 0.836 (95 percent CI, 0.73–0.94; p<0.001). Individuals in the highest pro-NT quartile had a greater risk of NAFLD (odds ratio, 2.62; 1.08–6.40) after adjustment for confounders.

“The association between higher pro-NT and NAFLD was confirmed in the second cohort independently from confounders,” researchers said.

In a recent study on mechanisms behind the link between higher pro-NT and the development of obesity and cardiometabolic diseases, Li and colleagues found significantly lower intestinal fat absorption in NT-deficient mice and protection toward high-fat diet-induced obesity, hepatic steatosis and insulin resistance compared with wild-type mice. [Nature 2016;533:411-415; JAMA 2012;308:1469-1475; Arterioscler Thromb Vasc Biol 2016;36:1692-1697]

Furthermore, mice with NTR3 deficiency are protected from high-fat diet-induced obesity and fatty liver. This signifies that NT-induced hepatic fat accumulation is facilitated by both NTR1 and NTR3. [J Hepatol 2015;62:175-181]

“In our study, higher pro-NT correlated with T2D and signatures of impaired glucose metabolism and insulin resistance, but not with adiposity... NAFLD represents an established cardiovascular risk factor and may determine and worsen insulin resistance, systemic inflammation, and metabolic complications of obesity,” researchers said. [J Clin Endocrinol Metab 2007;92:3490-3497; Proc Natl Acad Sci USA 2009;106:15430-15435; Gastroenterology 2008;134:1369-1375; N Engl J Med 2010;363:1341-1350]

“Indeed, we observed a linear association between pro-NT, hepatic damage in nonalcoholic steatohepatitis (NASH) and parameters related to glucose metabolism impairment,” they added.

The present cross-sectional study recruited 60 obese individuals undergoing bariatric surgery for clinical purposes. Further investigation was performed on the association between pro-NT and NAFLD in 260 consecutive patients referred to outpatient clinics for metabolic evaluations, including liver ultrasonography. Complete metabolic characterization was conducted in the entire study population, and liver biopsies were performed during surgery in the obese cohort.

“A possible weakness of this novel observation can be represented by the limited sample size of the cohort undergoing liver biopsy. However, obtaining samples for liver histology implies the use of invasive procedures, reasonably representing … a limiting factor for study enrolment,” researchers said.

NT is an intestinal peptide released by fat ingestion and promotes lipid absorption. Higher circulating NT levels are associated with T2D, obesity and cardiovascular disease, according to researchers.

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