Striatal dopamine receptor binding in morbidly obese women before and after gastric bypass surgery and its relationship with insulin sensitivity

Weijer, Barbara A. de; Giessen, Elsmarieke van de; Janssen, Ignace; Berends, Frits J.; Laar, Arnold van de; Ackermans, Mariëtte T.; Fliers, Eric; Fleur, Susanne E. la; Booij, Jan; Serlie, Mireille J.

doi:10.1007/s00125-014-3178-z

Cited by 50 publications

(55 citation statements)

References 10 publications

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“…The effect of RYGB on D2R signaling has been inconsistent in the literature. Clinical studies have found RYGB to increase in D2 availability (Steele et al, ; van der Zwaal et al, ), decrease D2 availability (Dunn et al, ) or produce no change at all (de Weijer et al, ; Karlsson et al, ; Wu, Garamszegi, Xie, & Mash, ). Since the autoradiography technique in our study removes any endogenous neurotransmitters in the synapse, we obtain an accurate reading of receptor expression without the confounding influence of competition from endogenous ligands seen in human PET studies.…”

Section: Discussionmentioning

confidence: 99%

Roux‐en‐Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels

Hamilton

Swenson²,

Hajnal

et al. 2018

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Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to four groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed. [ H]SCH 23390, [ H]Spiperone, and [ H]WIN35 428 autoradiography was performed to quantify the effects of diet and RYGB surgery on dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter (DAT) binding. Rats on a chronic HF diet became obese with reduced D1R-like binding within the ventrolateral striatum and the nucleus accumbens core, reduced D2R-like binding in all areas of the striatum and nucleus accumbens core and shell, and reduced DAT binding in the dorsomedial striatum. Restricted HF diet rats showed similar reductions in D1R-like and D2-R-like binding as the obese rats, and reduced DAT binding within all areas of the striatum. Both RYGB and restricted HF diet rats showed similar weight reductions, with RYGB rats showing no difference in binding compared to controls. The observed changes in binding between non-treated obese rats and RYGB rats demonstrates that HF dietary effects on the dopamine system were reversed by RYGB.

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Section: Discussionmentioning

confidence: 99%

Roux‐en‐Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels

Hamilton

Swenson²,

Hajnal

et al. 2018

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“…Dorsal striatal dopamine signaling is altered in the obese (Guo et al, 2014), and different studies reported partial normalization after bariatric interventions; however, according to these studies, the direction of the effect appears to depend on how receptor binding potential was measured (de Weijer et al, 2014; Dunn et al, 2010; Steele et al, 2010). Rodent models have also provided fruitful information linking the Roux-en-Y intervention to alterations in dorsal striatum monoamine homeostasis (Reddy et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite

et al. 2016

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Reductions in calorie intake contribute significantly to the positive outcome of bariatric surgeries. However, the physiological mechanisms linking the rerouting of the gastrointestinal tract to reductions in sugar cravings remain uncertain. We show that a duodenal-jejunal bypass (DJB) intervention inhibits maladaptive sweet appetite by acting on dopamine-responsive striatal circuitries. DJB disrupted the ability of recurrent sugar exposure to promote sweet appetite in sated animals, thereby revealing a link between recurrent duodenal sugar influx and maladaptive sweet intake. Unlike ingestion of a low-calorie sweetener, ingestion of sugar was associated with significant dopamine effluxes in dorsal striatum, with glucose infusions into the duodenum inducing greater striatal dopamine release than equivalent jejunal infusions. Consistently, optogenetic activation of dopamine-excitable cells of dorsal striatum was sufficient to restore maladaptive sweet appetite in sated DJB mice. Our findings point to a causal link between striatal dopamine signaling and the outcomes of bariatric interventions.

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“…Third, reduced brain reward center activation appears to be associated with a shift in food preference away from high-caloric-density foods (99,102). Fourth, changes in reward center activation following RYGBP are likely to be independent of striatal D2/3R availability (103). Finally, neural responsivity to food images in the long term (more than three years) in women who had undergone RYGBP resembled that of lean individuals, despite still remaining above normal weight (104).…”

Section: Human Observational Studiesmentioning

confidence: 99%