Pirjo Nuutila

Context Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied. Objective This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT. Methods Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre surgery and 3 months post surgery. Glucagon-like peptide-1 (GLP-1) infusions were performed in normal-weight participants. Cohort 3: Fasting pNT was assessed pre RYGB (n = 161), 2 months post RYGB (n = 92), and 1year post RYGB (n = 118) in NG and T2D patients. pNT levels were measured using enzyme-linked immunosorbent assay. Results Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post RYGB/VSG. GIP or GLP-1 infusion had no effect on pNT levels. Fasting pNTs were higher 1-year post RYGB regardless of glycemic status. Conclusion RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1, and higher fasting pNTs are maintained 1 year post surgically.

Objective Cannabinoid type 1 receptors (CB1R) modulate feeding behavior and energy homeostasis, and the CB1R tone is dysgulated in obesity. This study aimed to investigate CB1R availability in peripheral tissue and brain in young men with overweight versus lean men. Methods Healthy males with high (HR, n = 16) or low (LR, n = 20) obesity risk were studied with fluoride 18–labeled FMPEP‐ d 2 positron emission tomography to quantify CB1R availability in abdominal adipose tissue, brown adipose tissue, muscle, and brain. Obesity risk was assessed by BMI, physical exercise habits, and familial obesity risk, including parental overweight, obesity, and type 2 diabetes. To assess insulin sensitivity, fluoro‐[ 18 F]‐deoxy‐2‐D‐glucose positron emission tomography during hyperinsulinemic‐euglycemic clamp was performed. Serum endocannabinoids were analyzed. Results CB1R availability in abdominal adipose tissue was lower in the HR than in the LR group, whereas no difference was found in other tissues. CB1R availability of abdominal adipose tissue and brain correlated positively with insulin sensitivity and negatively with unfavorable lipid profile, BMI, body adiposity, and inflammatory markers. Serum arachidonoyl glycerol concentration was associated with lower CB1R availability of the whole brain, unfavorable lipid profile, and higher serum inflammatory markers. Conclusions The results suggest endocannabinoid dysregulation already in the preobesity state.