Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss

Zwaal, Esther M. van der; 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:10.1016/j.euroneuro.2016.04.009

Cited by 42 publications

(65 citation statements)

References 61 publications

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“…Interestingly, imaging studies showed quite consistently lower striatal dopamine D 2/3 -receptor binding in obese compared with non-obese subjects, which supports the hypothesis of a hypo-dopaminergic state in obese subjects (21). This lower D 2/3 -receptor binding can be explained by a lower expression and/or lower binding capacity for dopamine due to obesity-related conformational changes of the receptor (e.g., increased sensitivity of the receptor for dopamine).…”

Section: Discussionsupporting

confidence: 72%

Bromocriptine and insulin sensitivity in lean and obese subjects

Bahler

Verberne

Brakema

et al. 2016

Endocrine Connections

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Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening) results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC) 742 mmol/L * 120 min (695–818) vs 641 (504–750), P = 0.036, AUC for insulin did not change, P = 0.575). In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236–96,831) vs 36,448 (25,213–57,711), P = 0.012) and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614–988) vs 644 (568–829), P = 0.017) and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration.

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Section: Discussionsupporting

confidence: 72%

Bromocriptine and insulin sensitivity in lean and obese subjects

Bahler

Verberne

Brakema

et al. 2016

Endocrine Connections

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“…There is also increasing evidence that striatal dopamine plays a role in the regulation of energy homeostasis. We, and others, have shown that striatal dopamine D 2/3 receptor (D 2/3 R) availability is reduced in obese insulin-resistant humans (17,18) and increases after long-term bariatric surgery-induced weight loss (19). Neurons in the NAc can be activated or inhibited by glucose (20), and sucrose administration to rodents stimulates dopamine release within the NAc (21,22).…”

Section: Introductionmentioning

confidence: 99%

Striatal dopamine regulates systemic glucose metabolism in humans and mice

et al. 2018

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The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. First, we present the case of a diabetes patient who displayed strongly reduced insulin requirements after treatment with bilateral deep brain stimulation (DBS) targeting the anterior limb of the internal capsule. Next, we show that DBS in this striatal area, which induced dopamine release, increased hepatic and peripheral insulin sensitivity in 14 nondiabetic patients with obsessive-compulsive disorder. Conversely, systemic dopamine depletion reduced peripheral insulin sensitivity in healthy subjects. Supporting these human data, we demonstrate that optogenetic activation of dopamine D receptor-expressing neurons in the nucleus accumbens increased glucose tolerance and insulin sensitivity in mice. Together, these findings support the hypothesis that striatal neuronal activity regulates systemic glucose metabolism.

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“…Regarding a plausible underlying mechanism, recent studies have suggested changes in brain dopamine functions following bariatric surgery (Dunn, Cowan et al 2010, Steele, Prokopowicz et al 2010, de Weijer, van de Giessen et al 2014, Reddy, Wasserman et al 2014, Hankir, Ashrafian et al 2015, Blackburn, Hajnal et al 2016, Han, Tellez et al 2016, van der Zwaal, de Weijer et al 2016). In fact, dopamine and related brain areas have been shown to play a critical role in ethanol consumption and addiction (Tabakoff and Hoffman 2013, Vanderlinden, Saba et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling

Orellana

Jamis

Horvath

et al. 2018

Brain Research Bulletin

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Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most common surgical options for the treatment of obesity and metabolic disorder. Whereas RYGB may result in greater and more durable weight loss, recent clinical and pre-clinical studies in rats have raised concerns that RYGB surgery may increase risk for alcohol use disorder (AUD). In contrast, recent clinical reports suggest a lesser risk for AUD following VSG, although no preclinical studies have been done to confirm that. Therefore, the present study sought to determine the effects of VSG on ethanol intake and preferences in rodent models using protocols similar to those previously used in animal studies for RYGB. Male Sprague Dawley rats and male C57B6 mice were made obese on a high fat diet (60%kcal from fat) and received VSG or no surgery (controls). All animals then were given access to increasing concentrations of ethanol (2%, 4%, 6%, and 8%), presented for few days each. Compared to controls, VSG rats consumed significantly less of 2, 6 and 8% ethanol and showed significantly reduced preferences to 6 and 8% ethanol over water. VSG mice also displayed reduced intake and preference for 6 and 8% ethanol solutions. After a two-week period of forced abstinence, 8% ethanol was reintroduced and the VSG rats and mice continued to exhibit reduced consumption and less preference for ethanol. Regarding the underlying mechanism, we hypothesized that the removal of the ghrelin producing part of the stomach in the VSG surgery is a possible contributor to the observed reduced ethanol preference. To test for functional changes at the ghrelin receptors, the VSG and control rats were given IP injections of acyl-ghrelin (2.5nmol and 5nmol) prior to ethanol access. Neither concentration of ghrelin resulted in a significant increase in 8% ethanol consumption of VSG or control subjects. Next, the rats were given IP injections of the ghrelin receptor antagonist, JMV (2.5mg/kg body weight). This dose induced a significant reduction in 8% ethanol consumption in the VSG group, but no effect on ethanol intake in the controls. While ghrelin injection was uninformative, increased sensitivity to subthreshold doses of the ghrelin receptor antagonist may indicate reduced ghrelin signaling following VSG. Overall, these findings suggest that bariatric patients with increased susceptibility to AUD may benefit from receiving VSG instead of RYGB surgery, and that changes in ghrelin signaling, at least in part, may play a role in the differential AUD risks between the two most commonly performed bariatric surgical procedures.

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Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss

Cited by 42 publications

References 61 publications

Bromocriptine and insulin sensitivity in lean and obese subjects

Bromocriptine and insulin sensitivity in lean and obese subjects

Striatal dopamine regulates systemic glucose metabolism in humans and mice

Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling

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