SFEBES2015 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (108 abstracts)
1Warwick Medical School, University of Warwick, Coventry, West Midlands, UK; 2Aston Medical School, Aston University, Birmingham, West Midlands, UK; 3Institute of Endocrinology, Prague, Czech Republic; 4OB Clinic, Prague, Czech Republic; 5University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, UK; 6Institute of Digital Healthcare, University of Warwick, Coventry, West Midlands, UK.
Aims/hypothesis: Genetic and functional defects in mitochondria are linked with phenotypes of obesity, hypercholesterolemia, and type 2 diabetes (T2DM). However, the impact on mitochondria during surgery-induced metabolic recovery is unknown. We therefore studied the effect of restrictive versus malabsorptive bariatric procedures on indicators of mitochondrial efficiency and control of biogenesis/function.
Methods: Forty-three morbidly obese, T2DM consented women underwent restrictive (laparoscopic adjustable gastric banding, n=14; gastric plication, n=16) or malabsorptive (bilio-pancreatic diversion, n=13) operations in an ethics-approved study. Abdominal subcutaneous adipose tissue (AbScAT) biopsies taken before and 6 months after surgery were used to assess mitochondrial number (mtDNA copy number) and mRNA expression of biogenesis (PGC1α, POLG, TFAM), oxidative phosphorylation (mtND6, SDHA, COX4I1, mtATP6), and antioxidant related genes (SOD1, UCP2).
Results: Metabolic health of patients was significantly improved in both surgical interventions, although more marked in malabsorptive surgery, where 69% achieved T2DM remission (HbA1c<42 mmol/mol off T2DM medication) compared to only 33% in restrictive surgery. Mitochondrial efficiency in AbScAT was positive across all genes assessed in the malabsorptive surgery (mtATP6 r=0.898, P=0.0004), evidenced by correlation of change in mitochondrial number versus mRNA expression, whilst negative in the restrictive surgery (r=−0.316, P=0.123). Further analysis of mitochondrial inefficiency identified that PGC1α (29.5%, P=0.004), SOD1 (11.7%, P=0.019) and HDL (18.3%, P=0.008) levels were significant independent predictors of this event. Finally, T2DM remission was also associated with tighter control of UCP2 and mitochondrial number in response to nutrient excess, as denoted by correlation with BMI (P=0.004) and HbAlc (P=0.0003) respectively; again more marked in malabsorptive surgery.
Conclusions/interpretation: Malabsorptive surgery led to marked improvement in metabolic health, enhanced mitochondrial efficiency and higher T2DM remission than restrictive surgery. Taken together this data suggests that AbdScAT may act as an important site for mitochondrial improvement supporting metabolic recovery, particularly in cases where nutrient absorption is severely limited rather than purely restricted.