Neudesin, a Novel Regulator of Energy Metabolism in Obesity and Type 2 Diabetes Mellitus—The Effect of Acute Fasting and Endoscopic Duodenal-Jejunal Bypass Liner Implantation

Abstract

Neudesin has recently been identified as a negative regulator of energy expenditure in experimental animals; however, its role in humans remains unexplored. The aim of our study was to assess the effects of obesity and type 2 diabetes mellitus along with selected interventions including acute fasting and endoscopic duodenal-jejunal by-pass liner implantation (DJBL) on its serum levels and adipose tissue mRNA expression. Fifteen obese T2DM subjects undergoing DJBL implantation, 15 subjects with functional hypoglycemia subjected to 72-hour fasting (Fast) and 12 healthy controls (C) were included in the study. Samples were taken at baseline and 6 and 10 months after DJBL and after 78 hours of fasting and 2 hours after realimentation, respectively. Serum neudesin was measured using ELISA kit (Neudesin Human ELISA, Biovendor, CR). qRT PCR was used to detect mRNA expression of neudesin in white adipose tissue (WAT). Baseline serum neudesin levels were comparable between all groups (1.77 ± 0.86 vs. 1.74 ± 0.54 vs. 1.88 ± 0.70 ng/ml, n.s. for DJBL vs. Fast vs. C). Along with reduction in body weight (BMI 42.8 ± 6.53 vs. 36.6 ± 4.91 kg/m², p=0.038) and improvement of HbA_1c (73.5 ± 17.2 vs. 50.0 ± 12.6 mmol/mol, p=0.001) DJBL increased serum neudesin at 6 and 10 months after procedure (1.77 ± 0.86 vs. 2.28 ± 1.27 vs. 2.13 ± 1.02 ng/ml, p=0.001 for baseline vs. 6 vs. 10 months), while having no effect on neudesin mRNA expression in WAT. In contrast, acute fasting decreased serum neudesin during the whole period (1.74 ± 0.54 vs. 1.46 ± 0.48 ng/ml, p=0.001 for baseline vs. 72 hours) with no impact of subsequent realimentation (1.37 ± 0.44 ng/ml, n.s. 2 h postprandially).To conclude, serum neudesin levels are regulated differently during acute fasting and chronic weight reduction induced by DJBL. Further studies are needed to assess its potential in the treatment of obesity and T2DM.