Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception.

BACKGROUND:Roux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure's impact on the brain. This study examined the effects of RYGB on the brain's response to the anticipation of highly palatable versus regular food. METHODS:High fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber. After CPP, animals were placed in either chamber without the food stimulus, and brain-glucose metabolism (BGluM) was measured using positron emission tomography (μPET). RESULTS:Bacon CPP was only observed in RYGB rats that had stable weight loss following surgery. BGluM assessment revealed that RYGB selectively activated regions of the right and midline cerebellum (Lob 8) involved in subjective processes related to reward or expectation. Also, bacon anticipation led to significant activation in the medial parabrachial nuclei (important in gustatory processing) and dorsomedial tegmental area (key to reward, motivation, cognition and addiction) in RYGB rats; and activation in the retrosplenial cortex (default mode network), and the primary visual cortex in control rats. CONCLUSIONS:RYGB alters brain activity in areas involved in reward expectation and sensory (taste) processing when anticipating a palatable fatty food. Thus, RYGB may lead to changes in brain activity in regions that process reward and taste-related behaviors. Specific cerebellar regions with altered metabolism following RYGB may help identify novel therapeutic targets for treatment of obesity

Scan day flow chart.

<p>Each animal was scanned twice, separately in the presence of either bacon- or chow-paired cues, but without either food stimulus. Animals were conscious during the uptake phase, and immediately prior to and during acquisition (20 min scan), animals were anesthetized with continuous isoflurane. During the 2-day break, CPP was maintained with one conditioning session per day (not shown).</p

Gastric bypass effectively reduced body weight following diet-induced obesity.

<p>Pre-operative body weights during diet-induced obesity (establishment phase) are shown in the shaded region. Weight loss following surgery, specific to the RYGB animals, is shown in the non-shaded region, with a more pronounced difference in the Q2/3/4 sub-group. The inset shows the differences in body weights, following group-assignment, the day before experimental or sham surgeries (*<i>p</i>< 0.05 compared to Sham-ND; no difference between Q1 and Q2/3/4 before surgery, not shown).</p

Food intake throughout the conditioning sessions.

<p>Animals were given 10-minutes to consume 5-grams of either bacon or chow during the final 10 min of each conditioning session. Irrespective of group, animals consumed more bacon than chow throughout the conditioning-component, suggesting that relative to chow, bacon was highly palatable. Cumulative intake is the sum grams consumed between CPP days 1 and 12 for each food-stimulus (arrows indicate Test Days 1 and 2; thick line: <i>p</i> < 0.05 for bacon versus chow on the given days; *<i>p</i> < 0.05 for bacon versus chow in a specific group). The only significant differences observed were found between bacon and chow (Sham-ND and Sham-PF).</p

Weekly food and water intake during bacon- and chow-conditioning.

<p>Weekly food <b>(A)</b> and water <b>(B)</b> intakes were calculated relative to CPP Weeks 1 and 2, and these values, expressed in calories and volume consumed, respectively, were adjusted based on body-weight (*unadjusted <i>p</i> < 0.001 versus Sham-AL,-PF and-ND; ^~unadjusted <i>p</i> < 0.001 versus Sham-PF and-AL; ^#unadjusted <i>p</i> < 0.007 versus all groups).</p

Healthy RYGB rats (Q1) showed significant bacon CPP.

<p>To quantify preference for the bacon-paired chamber, the amount of time each animal spent in the bacon-paired chamber was standardized to total time in both chambers. There was a bypass-specific increase in bacon-chamber preference after conditioning (Test Days 1 and 2) relative to Habituation Day, yet importantly, this behavioral response was strictly observed in the RYGB animals that responded well to the surgery (*unadjusted <i>p</i> < 0.05 compared to Habituation Day).</p

SPM Results.

<p>Statistical Parametric Mapping (SPM) results showing significant clusters and statistical parameters for the contrast Bacon>Chow in rats that underwent gastric bypass surgery (RYGB) and sham-operated controls (AL). The contrast Chow>Bacon did not yield any significant clusters. (MPB) medial parabrachial nucleus, (DMTg) dorsomedial tegmental area (Sim) simple lobule.</p><p>SPM Results.</p

Objective health-screen and bypass outcome.

<p>As gross health and weight were highly variable in the experimental group, compared to the sham-operated controls, relative weight-loss after gastric bypass was calculated and used to objectively determine these animals’ health. <b>(A)</b> The 7 RYGB animals with the lowest and most stable weight-losses (Q1) were compared to the remaining 75% (**<i>p</i>< 0.01 compared to each other; Sham-AL shown as reference). <b>(B)</b> This objective separation was valid, as differences in mortality were explained by the screen.</p

Statistical Parametric Mapping (SPM) showing regional brain activation to bacon-paired cues in rats that underwent gastric bypass surgery (RYGB; blue) or sham-operated controls fed a HF diet (green).

<p>SPM clusters were overlaid onto a magnetic resonance imaging atlas of the rat brain set to stereotaxic coordinates and significant clusters were outlined in the Paxinos rat brain atlas. (RS-retrosplenial cortex; V1M-primary visual cortex; IC-inferior colliculus; MPB-medial parabrachial nucleus; DMTg-dorsomedial tegmental area; Sim/SimB- simple lobule; CB(8)-cerebellum lobule 8).</p