Bariatric surgery is currently the only effective treatment for morbid obesity. The Laporascopic Adjustable Gastric Band (LAGB) is employed extensively in Australia. LAGB is effective in reducing excess weight for at least 15 years; however there are a subset of individuals who fail to lose appreciable amounts of weight. Weight loss, including that induced by bariatric surgery is associated with a compensatory reduction in energy expenditure which confounds long term maintenance of weight loss. Adjuvant therapies may be used to improve weight loss outcomes by ameliorating or even reversing this reduction in energy expenditure.
Initial proof of concept experiments involved the administration of thyroxine, which is well characterised for its potent effects on energy expenditure, as an adjunct to gastric banding. Rats were either fitted with an AGB or sham operated and received either thyroxine (100ug/kg/day) or vehicle (n=6-8/group) over 4 weeks. Subsequent experiments involved the administration of bupropion/naltrexone (Contrave, currently under consideration by the FDA), in combination with AGB inflation. Metabolic parameters, including food intake, body weight, fat mass and energy expenditure in BAT and whole body calorimetry were assessed.
Inflation of the AGB caused a reduction in body weight gain that was further enhanced by co-treatment with thyroxine or Contrave. AGB induced weight loss is associated with a reduction in BAT thermogenesis. Thyroxine ameliorates the reduction in AGB-induced BAT thermogenesis. Contrave elevated BAT thermogenesis, which was also reflected in an increase in whole body energy expenditure. When AGB inflation was combined with thyroxine or Contrave treatment, AGB-induced reductions in adiposity were further enhanced.
These data show that adjuvant therapies may improve the efficacy of the AGB, provide an insight into the underlying mechanisms and open the door to the assessment of combination therapies in the clinic to enhance weight loss.