Effect of Bariatric Surgery on Neuroplasticity in Humans

Abstract

Background and Aim: Obesity and diabetes are associated to increased risk of cognitive impairment, neurodegenerative disorders, neuroinflammation and synaptic plasticity abnormalities. The aim of the study was to evaluate the effect of obesity and bariatric surgery on neural plasticity (NP). Methods: We recruited 20 normal weight subjects (NS; age 26±10 years, BMI 21.7±2.6 kg/m2) and 31 obese subjects (OB; 40±11 years; BMI: 41.6±6.7 kg/m2) in whom NP in the visual cortex was measured as change in ocular dominance after 120 min of monocular deprivation obtained by ocular patch. To explore the effect of body weight reduction on NP, 14 OB (BMI=45.7±1.6 kg/m2) underwent metabolic surgery (RYGB) and NP was measured 6 months after surgery. Hormonal and metabolic parameters were obtained before and after administration of 75g glucose (OGTT). Results: At baseline NP was lower in OB than in NS (0.04±0.vs. 0.12±0.05, p<0.0001). NP was inversely correlated with body weight (r= -0.55; p<0.001). Six-months after RYGB, BMI was markedly reduced (34.3±1.6 kg/m2; p<0.001 vs. baseline) and glucose metabolism improved (HOMA-IR from 4.7±0.9 to 1.6±0.4; P=0.0and Disposition Index from 0.07±0.02 to 0.81±0.30 mUI × ml-1/ mg × dl-1× 1/ mUI × ml-1; p< 0.05). Post-OGTT GLP-1 levels increased (AUCOGTTfrom 5457±715 to 11215±1067 pmol/l×120min; P<0.002). NP showed a 10-fold increase (0.01± 0.03 to 0.10±0.04; p=0.008) indicating restoration of visual plasticity. The NP increase was correlated to increase in active GLP-1 (r=0.86; p<0.007) and BMI reduction (r=0.10; p=0.07). Conclusion: NP is markedly altered in OB, and it is restored to normal after RYGB. The relationship between NP increase and circulating GLP-1 levels suggests a potential role of this hormone in the NP restoration in humans. Disclosure G. Daniele: None. A. Dardano: None. C. Lunghi: None. P. Binda: None. A. Ciccarone: None. F. Santini: None. G. Ceccarini: None. L. Giusti: None. R. Bellini: None. M. Seghieri: None. S. Del Guerra: None. C. Moretto: None. M. Morrone: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Servier, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals U.S.A., Inc.. Advisory Panel; Self; Janssen Biotech, Inc., Abbott.