Weight Loss by Low-Calorie Diet Versus Gastric Bypass Surgery in People With Diabetes Results in Divergent Brain Activation Patterns: A Functional MRI Study

<b>Objective: </b>Weight loss achieved with very low-calorie diets (VLCD) can produce remission of Type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesised that in patients living with obesity and pre-diabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference. <b>Methods:</b> 16 participants underwent gastric bypass surgery and 19 matched participants undertook a very low calorie (meal replacement) diet for 4 weeks. Brain responses to food cues and resting state functional connectivity was assessed with functional MRI pre- and post-intervention and compared across groups. <b>Results:</b> We show that RYGB results in three divergent brain responses in comparison to VLCD-induced weight loss: (i) VLCD resulted in increased brain reward centre food cue responsiveness whereas in RYGB this was reduced; (ii) VLCD resulted in higher neural activation of cognitive control regions in response to food cues, associated with exercising increased cognitive restraint over eating, whereas RYGB did not; (iii) a homeostatic appetitive system (centred on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD. <b>Conclusion:</b> Taken together these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast with the enduring weight loss after RYGB.