Background

Metabolic surgery reduces cardiovascular risk and disease in patients with obesity and type 2 diabetes. We aimed to investigate if duodenal-jejunal bypass (DJB) can influence cardiac metabolism independent of weight loss.

Methods

Rats with high fat diet-induced obesity underwent either DJB or a sham operation and pair-feeding. Hearts were harvested 4 weeks after surgery to investigate the effects of DJB on genes and proteins involved in glucose transport, oxidative phosphorylation, gluconeogenesis, glycolysis, glycogen synthesis, β-fatty acid oxidation. In an additional set of experiments DJB-rats and sham-operated controls underwent M-mode echocardiogram to measure cardiac function.

Results

Despite no differences in food intake and body weight, DJB rats had 2.4-fold higher mRNA levels of glucose transporter 1 (GLUT-1) compared to sham-operated animals (p<0.05). No differences were found in the expression of other glucose transporters (Glut4, Sglt1, Sglt-2) or β fatty acid oxidation. Deep sequencing experiments showed up-regulation of ATP-synthase and oxidative phosphorylation in myocardial mitochondria of DJB rats. Hexokinase-2 mRNA, a marker of glycolysis, was 40% higher in DJB rats (p=0.28). DJB-rats also had higher levels of GSK3β protein (p<0.01), indicating up-regulation of glycogen synthesis and lower Pck1 mRNA levels (p<0.05) indicating down-regulation of gluconeogenesis. DJB rats had higher ejection fraction (78.3+6.9% vs 72.5+2.8%; p=0.043), fractional shortening (50.3+9.1% vs 42,4+2.3% p=0.03), and cardiac output (86.2+23.4% vs 65.6+6.3%; p=0.03) compared to sham animals, consistent with improved cardiac function.

Conclusions

This study shows that DJB can induce weight-independent effects on cardiac metabolism with up-regulation of insulin-independent glucose uptake (GLUT-1) and increased ATP production. These effects could contribute to improved cardiac efficiency and confer protection from cardiac disease.