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

Abstract

OBJECTIVE Weight loss achieved with very-low-calorie diets (VLCDs) 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 hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference. RESEARCH DESIGN AND METHODS Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups. RESULTS We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1 ) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2 ) 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; and 3 ) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD. CONCLUSIONS 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 to enduring weight loss after RYGB.

Regulation of body weight: Lessons learned from bariatric surgery

“…Applied to bariatric surgery, most studies demonstrate normalization of impaired activity and/or connectivity patterns in the obese (before surgery) towards patterns observed in lean controls (VSG [ [155] , [156] , [157] , [158] ], RYGB [ 155 , [159] , [160] , [161] , [162] , [163] , [164] , [165] ]). In one study presurgical functional connectivity predicted the magnitude of weight loss induced by VSG [ 166 ], and another study found that activation of cortical areas involved in inhibitory control was significantly greater after RYGB compared to VSG [ 155 ].…”

“…One significant issue for many of the above studies is the inability to distinguish the direct effects of the surgery from the resulting weight loss. Only one study compared low-calorie diet vs. gastric bypass surgery in order to distinguish between surgery-specific and weight loss-specific effects [ 161 ]. In a cohort of mostly female patients with obesity and type-2 diabetes, fMRI scans capturing the response to food cues in the fed versus fasted state were conducted before and 4 weeks after either very low calorie diet (VCLD) or RYGB.…”

“…In a cohort of mostly female patients with obesity and type-2 diabetes, fMRI scans capturing the response to food cues in the fed versus fasted state were conducted before and 4 weeks after either very low calorie diet (VCLD) or RYGB. Compared to VLCD there was a relative reduction in food cue responsiveness in food reward brain areas, a strengthening of cognitive control regions, and reduced activation in the hypothalamus with increased connectivity to reward areas 4 weeks after RYGB [ 161 ]. This may suggest that reduced hunger after RYGB is driving the changes in food reward and that overall RYGB makes it easier to sustain weight loss compared to VLCD.…”

Mechanisms of bariatric surgery for weight loss and diabetes remission

“…Now, increasing studies have used fMRI to observe changes in brain activity in response to food cues in an effort to gain a deeper understanding about the mechanisms of BS. RYGB resulted in different brain responses compared with a very‐low‐calorie diets in clinical trials: RYGB resulted in a more active homeostatic appetite system, as well as reduced neural activation in response to food cues in cognitive control regions and responsiveness to food cues in the reward center of the brain, 192 resulting in favorable changes in food rewards and preferences 10,193 . Another study, by utilizing functional brain imaging, reported that brain responses to high‐fat milkshake cues normalized at 1 year following RYGB in obese participants 194 .…”

“…For example, topiramate may cause increased pulse and blood pressure in certain patients and increase the risk of oral clefts in infants when taken by pregnant women; liraglutide has obvious gastrointestinal side effects, such as nausea, vomiting, diarrhea, and an increased risk of pancreatitis 8 . Moreover, short‐term weight control is easily achieved by the means described, but it is prone to weight regain 9,10 . There are certain advantages in maintaining long‐term weight loss for bariatric surgery (BS) in severely obese patients 7,11 .…”