Aim: Obesity and glucose metabolism disorders are associated with accelerated age-related cognitive decline, deterioration of plasticity and metabolic homeostasis in the brain. Gut hor- mones act upon central circuits and exert an important role in the homeostasis of glucose metabolism. We aimed to evalu- ate the impact of bariatric surgery (RYGB) on the brain glucose metabolism and to access the possible relationship between cerebral metabolic rate of glucose (MRGlu) and gut hormones changes at 6 months after RYGB. Materials and methods: Elev- en obese subjects with normal glucose tolerance (BMI 45.8±4.9 kg/m2; HbA1c 41.5±5.4 mmol/mol; age 43.7±9.5 years) under- went anoral glucose tolerance test (OGTT) followed by 60 min- utes 18F-FDG (185 ± 100 MBq) dynamic PET study beforeand 6 months after RYGB. Gut hormones, leptin and brain derived neurotrophic factor (BDNF) were assessed at baseline and 6 months after RYGB. Arterial input function was obtained by the first-pass of FDG from a manually drawn carotid artery region (PMOD software). Continuous venous samples were collected to scale image derived input curves and to correct for spill-in/ spill-out. The two tissue compartment Patlak approach was used to calculate the MRGlu. Parametric MRGlu images were than created and spatially normalized in MNI space. Within-sub- ject ANOVA and voxel-wise paired t-test were used to assess the changes of the mean substrates values. To determine within-in- dividual association for paired measures the repeated measures correlations (rmcorr) were performed. Results: Six months after RYGB a significant BMI reduction (p<0.001) was observed. Post- OGTT GLP1 was increased (5336±2263 to 11132±3412 pmol/l x 120min; p<0.05) as well as GIP (4140±3659 to 5791±4537 pg/ ml x 120min; p=0.01). VIP and BDNF levels did not change 6m after RYGB, while fasting plasma leptin decreased (73.8±45.5 to 14.3±5.9 pmol/l; p<0.008). Voxel-wise paired analysis displayed clusters of decreased MRGlu 6 months after RYGB (p=0.005, kE > 100, uncorrected) in the wide-spread brain regions. At the intra-individual level, rmcorryields a strong positive relationship between MRGlu in the brain clusters and BMI (rrm = 0.74, 95% CI, p = 0.006) and leptin (rrm = 0.78, 95% CI, p = 0.003). Inverse asso- ciation was depicted between MRGlu in the brain clusters and pre-OGTT active GLP-1 (rrm = - 0.6, 95% CI, p < 0.05). Conclusion: Our findings imply a synergistic link between changes of circu- lating gut hormone levels and cerebral metabolism following the bariatric surgery. Further studies are needed to perceive the interplay between modulated gut homeostasis and the behav- ioral/cognitive changes after RYGB.
The effects of bariatric surgery on the brain glucose metabolism and its biological mediators: an insight from dynamic 18F-FDG PET/CT study
G. AghakhanyanPrimo
;G. Daniele;A. Dardano;L. Giusti;G. Ceccarini;F. Santini;A. Ciccarone;F. Guidoccio;S. Del Prato;D. Volterrani
2018-01-01
Abstract
Aim: Obesity and glucose metabolism disorders are associated with accelerated age-related cognitive decline, deterioration of plasticity and metabolic homeostasis in the brain. Gut hor- mones act upon central circuits and exert an important role in the homeostasis of glucose metabolism. We aimed to evalu- ate the impact of bariatric surgery (RYGB) on the brain glucose metabolism and to access the possible relationship between cerebral metabolic rate of glucose (MRGlu) and gut hormones changes at 6 months after RYGB. Materials and methods: Elev- en obese subjects with normal glucose tolerance (BMI 45.8±4.9 kg/m2; HbA1c 41.5±5.4 mmol/mol; age 43.7±9.5 years) under- went anoral glucose tolerance test (OGTT) followed by 60 min- utes 18F-FDG (185 ± 100 MBq) dynamic PET study beforeand 6 months after RYGB. Gut hormones, leptin and brain derived neurotrophic factor (BDNF) were assessed at baseline and 6 months after RYGB. Arterial input function was obtained by the first-pass of FDG from a manually drawn carotid artery region (PMOD software). Continuous venous samples were collected to scale image derived input curves and to correct for spill-in/ spill-out. The two tissue compartment Patlak approach was used to calculate the MRGlu. Parametric MRGlu images were than created and spatially normalized in MNI space. Within-sub- ject ANOVA and voxel-wise paired t-test were used to assess the changes of the mean substrates values. To determine within-in- dividual association for paired measures the repeated measures correlations (rmcorr) were performed. Results: Six months after RYGB a significant BMI reduction (p<0.001) was observed. Post- OGTT GLP1 was increased (5336±2263 to 11132±3412 pmol/l x 120min; p<0.05) as well as GIP (4140±3659 to 5791±4537 pg/ ml x 120min; p=0.01). VIP and BDNF levels did not change 6m after RYGB, while fasting plasma leptin decreased (73.8±45.5 to 14.3±5.9 pmol/l; p<0.008). Voxel-wise paired analysis displayed clusters of decreased MRGlu 6 months after RYGB (p=0.005, kE > 100, uncorrected) in the wide-spread brain regions. At the intra-individual level, rmcorryields a strong positive relationship between MRGlu in the brain clusters and BMI (rrm = 0.74, 95% CI, p = 0.006) and leptin (rrm = 0.78, 95% CI, p = 0.003). Inverse asso- ciation was depicted between MRGlu in the brain clusters and pre-OGTT active GLP-1 (rrm = - 0.6, 95% CI, p < 0.05). Conclusion: Our findings imply a synergistic link between changes of circu- lating gut hormone levels and cerebral metabolism following the bariatric surgery. Further studies are needed to perceive the interplay between modulated gut homeostasis and the behav- ioral/cognitive changes after RYGB.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
