Altered reward responses to sweet taste: a potential mechanism for weight loss after obesity surgery
Final Report Abstract
Currently, the most powerful therapy for obesity is bariatric surgery both in terms of significant weight loss and long-term efficacy . The most common operations are gastric banding (GB) and Roux-en-Y gastric bypass (RYGB). As GB is associated with a high number of reoperations and beneficial only to a limited number of patients, most surgeons regard the RYGB operation as “gold standard” for obesity treatment. Whilst RYGB ameliorates or even cures Type 2 Diabetes, it also has profound effects on hypertension, potentially due to improvements in serum inflammatory parameters and urinary cytokines associated with renal disease. However, the underlying mechanisms by which RYGB induces and sustains weight loss are poorly understood. Mechanisms include reduced hunger and increased satiation, which are presumably mediated by alterations in gastrointestinal and central neuroendocrine circuits. As these circuits may also regulate total energy expenditure (TEE), it has been hypothesized that RYGB increases TEE. Supporting this, I have demonstrated a higher TEE in rats after RYGB compared to ad libitum fed and body weight-matched sham controls. After a 5 g test meal RYGB rats had a greater cumulative increase in TEE suggesting that differences in dietinduced thermogenesis may play a role. Furthermore, the postoperative TEE increase potentially represents a higher energy requirement, as the small intestine showed significant morphometric changes with a 72% increase of total small bowel weight postoperatively. The gut is metabolically very active and gut hypertrophy potentially explains a higher maintenance energy requirement that contributes to body weight loss. Another potential mechanism for weight loss after RYGB includes changes in food preference. In fact, RYGB patients often report idiosyncratic changes in taste perception that involves “sweet” taste and a calorie-dense food. Concordantly, I found that rats after RYGB exhibit a shift away from high to low fat food. Furthermore, RYGB reduces rats’ preference for sucrose and lipid solutions. Whilst dopamine tissue levels in major brain reward areas were unchanged after RYGB, the reduced preference for high fat food was partly due to conditioned taste aversion. In addition, RYGB patients have an increased sucrose detection sensitivity compared with before surgery and controls. By elucidating the mechanisms by which RYGB reduces consumption of high fat foods, new therapies could be developed that mimic these mechanisms and so promote safe and effective weight loss.
Publications
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Gastric bypass increases energy expenditure in rats. Gastroenterology 2010 May;138(5):1845-53
Bueter M, Löwenstein C, Olbers T, Wang M, Cluny NL, Bloom SR, Sharkey KA, Lutz TA, le Roux CW
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Vagal sparing surgical technique but not stoma size affects body weight loss in rodent model of gastric bypass. Obesity Surgery 2010 May;20(5):616- 22
Bueter M, Löwenstein C, Ashrafian H, Hillebrand J, Bloom SR, Lutz TA, Olbers T, le Roux CW
