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

Autor: Arnold van de Laar, Mireille J. Serlie, Frits J. Berends, Susanne E. la Fleur, Eric Fliers, Ignace M. C. Janssen, Elsmarieke van de Giessen, Barbara A. de Weijer, Jan Booij, Mariëtte T. Ackermans
Přispěvatelé: Other departments, Nuclear Medicine, Other Research, Endocrinology Laboratory, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Amsterdam Neuroscience, Endocrinology
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Diabetologia, 57(5), 1078-1080. Springer Verlag
Diabetologia
ISSN: 0012-186X
Popis: To the Editor: There is evidence that certain brain areas are functionally altered in obesity. In obese humans, we and others have reported a reduction in dopamine D2/3 receptor (D2/3R) binding in the striatum, an important component of the brain reward system [1–3]. The neurotransmitter dopamine is important for the reinforcing value of food and it has been shown that food can induce a release of endogenous dopamine in the striatum [4]. Obese individuals are thought to be more sensitive to food reinforcement than those who are non-obese. This may underlie the notion that obese humans experience an increased craving for food. In addition, striatal D2/3R availability has been linked to craving and diet-induced obesity [5]. Therefore, it is plausible that dopamine-related mechanisms linked to craving and impulsiveness play a role in the development and pathophysiology of obesity. At present, it is unclear whether lower D2/3R availability is a cause or an effect of obesity. If the latter is true, one would expect that the reduced D2/3R availability observed in obese humans is reversed following the loss of a clinically significant fat mass or during a hypoenergetic state. Obesity is associated with insulin resistance. Insulin receptors are widely expressed in the human brain, and a relationship between insulin sensitivity and central dopamine signalling has been suggested [6]. It needs to be determined, therefore, whether the striatal D2/3R binding potential correlates with hepatic or peripheral insulin sensitivity. To determine whether the previously reported reduction in D2/3R availability in obese humans is reversible, we studied striatal D2/3R availability before and 6 weeks after Roux-en-Y gastric bypass (RYGB) surgery in 19 morbidly obese women. Eighteen of these patients participated in a study on the short-term metabolic effects of RYGB surgery (NTR1548; for one additional patient only single photon emission computed tomography [SPECT] data could be acquired) [3]. Informed consent was obtained from all participants and the study was approved by the local medical ethics committee of the Academic Medical Center in Amsterdam. We assumed that a difference of 15% in D2/3R availability would be of clinical relevance. A power analysis indicated that we would be able to detect this difference in a study group of 18 individuals. In the morbidly obese women, striatal D2/3R availability was assessed using a brain-dedicated SPECT scanner and [123I]iodobenzamide (bolus/constant infusion technique). Acquisition, attenuation correction, reconstruction and analyses of SPECT data were performed as previously described [1]. Apart from a classic region-of-interest (ROI) analysis, data also underwent an MRI-driven analysis. In this additional analysis, SPECT images were co-registered to individual MR images, and ROIs were drawn for the caudate nucleus and putamen separately and for the occipital cortex (representing non-specific binding) on the MR images [7]. Insulin sensitivity was determined before surgery by a two-step hyperinsulinaemic–euglycaemic clamp using a stable glucose isotope tracer [8]. Data for four women were not complete owing to technical failures and were excluded from analysis. The women had a mean age of 40.4 ± 8 (26–49) years (mean ± SD [range]). Weight loss 6 weeks after RYGB was 14 ± 4.6 (8–24) kg, which resulted in a significant reduction in BMI after surgery (before surgery 45.7 ± 6.3 [38.7–61.3] and after surgery 40.9 ± 6.3 [34.1–57.6] kg/m2; p
Databáze: OpenAIRE
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