Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects

Weijer, Barbara A. de; Giessen, Elsmarieke van de; Amelsvoort, Thérèse A. van; Boot, Erik; Braak, Breg; Janssen, Ignace; Laar, Arnold van de; Fliers, Eric; Serlie, Mireille J.; Booij, Jan

doi:10.1186/2191-219x-1-37

Cited by 157 publications

(166 citation statements)

References 20 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…4,5 However, the mechanisms of action underlying this decrease remain poorly understood. Midbrain leptin receptors may have a role, as they mediate the decrease in extracellular dopamine levels in the nucleus accumbens (NAcc) by a HF diet.…”

mentioning

confidence: 99%

High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity

et al. 2012

View full text Add to dashboard Cite

High-energy diets that induce obesity decrease striatal dopamine D 2/3 receptor (DRD 2/3 ) availability. It is however poorly understood which components of these diets are underlying this decrease. This study assessed the role of saturated fat intake on striatal DRD 2/3 availability. Forty rats were randomized to a free-choice high-fat high-sugar diet (HFHS) or a standard chow diet for 28 days. Striatal DRD 2/3 availability was measured using 123 I-IBZM storage phosphor imaging at day 29. The HFHS group was split in a HFHS-high-fat (HFHS-hf) and HFHS-low-fat (HFHS-lf) group based on the percentage energy intake from fat. Rats of both HFHS subgroups had increased energy intake, abdominal fat stores and plasma leptin levels compared with controls. DRD 2/3 availability in the nucleus accumbens (NAcc) was significantly lower in HFHS-hf than in HFHS-lf rats, whereas it was similar for HFHS-lf and control rats. Furthermore, DRD 2/3 availability in the NAcc was positively correlated with the percentage energy intake from sugar. Total energy intake was lower for HFHS-hf than for HFHS-lf rats. Together these results suggest that a diet with a high fat/carbohydrate ratio, but not total energy intake or the level of adiposity, is the best explanation for the decrease in striatal DRD 2/3 availability observed in diet-induced obesity.International Journal of Obesity (2013) 37, 754-757; doi:10.1038/ijo.2012.128; published online 7 August 2012Keywords: free-choice high-fat high-sugar diet; diet-induced obesity; dopamine D 2/3 receptor; striatum; energy intake; saturated fat INTRODUCTION High-fat (HF) and cafeteria diets induce obesity in rodents and decrease striatal dopamine D 2/3 receptor (DRD 2/3 ) levels [1][2][3] Imaging studies in humans also demonstrate that striatal DRD 2/3 availability is lower in obese subjects. 4,5 However, the mechanisms of action underlying this decrease remain poorly understood. Midbrain leptin receptors may have a role, as they mediate the decrease in extracellular dopamine levels in the nucleus accumbens (NAcc) by a HF diet. 6 In addition, knockdown of the dopamine D 2 receptor in the striatum is associated with increased reward deficiency and compulsive eating behavior in rats.1 This can be related to the alternative hypothesis that low DRD 2/3 levels might be a downregulation due to overstimulation of the dopamine system by repetitive food intake in obesity. 4 It remains unclear though whether increased total energy intake by high-energy diets or specific dietary components (for example, saturated fat, carbohydrates) underlie the induction of lower striatal DRD 2/3 levels.We previously showed that rats on a choice diet with saturated fat and a sugar solution (high-fat high-sugar, HFHS) become hyperphagic and obese. 7 We observed that some rats prefer saturated fat whereas others prefer the sugar solution although they all become obese. This variety allows us to determine whether diet composition or total energy intake is involved in DRD 2/3 downregulation. As we recently demonstrated that ra...

show abstract

mentioning

confidence: 99%

High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Nos EUA, as taxas de sobrepeso e obesidade estão em constante aumento, com cerca de 35% da população adulta de ambos os sexos obesa, enquanto a taxa em adolescentes e crianças obesos chega até 15 a 30% 36 . Isso pôde ser evidenciado no fato de a maioria dos estudos (12 dos 17) ter sido conduzida nos EUA [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] .…”

Section: Métodounclassified

“…Injeção de dopamina e L-Dopa levou à redução no consumo de alimento. original Uma correlação negativa entre o IMC e a disponibilidade dos receptores D2/D3 foi traçada em um estudo com mulheres obesas e não-obesas: estes receptores estavam 23% menos expressos no estriado das mulheres obesas 33 . Em estudo experimental, também foi encontrada essa correlação 19 .…”

Section: Rev Neurocienc 2014;22(3):373-380unclassified

Influence of dopamine and its receptors in the genesis of obesity: systematic review

Santos¹,

Souza²,

Oliveira³

et al. 2014

RNC

View full text Add to dashboard Cite

original RESUMO Introdução.A obesidade pode ser considerada um dos principais problemas de saúde pública mundial, com números alarmantes ao redor do mundo e correlação com diversas doenças de curso fatal. Fatores ambientais e vários sistemas fisiológicos estão implicados na causa da doença. Um destes sistemas, o de recompensa alimentar que envolve o neurotransmissor dopamina, é amplamente conhecido na literatura como responsável pela motivação à busca de recompensas naturais (alimentos) e artificiais (drogas). Objetivo. Levantar dados na literatura que comprovem o envolvimento da dopamina com a hiperfagia e obesidade. Método. Foi realizada pesquisa em três bases de dados (MedLine, Lilacs e SciELO) com descritores e termos livres relacionados ao assunto, no período de maio/2013 a março/2014. Resultado. Foram encontrados 391 artigos. Após seleção criteriosa, com base nos critérios de exclusão definidos para este trabalho, apenas 17 artigos foram selecionados para discussão, os quais foram unânimes em apontar mudanças no sistema dopaminérgico em participantes obesos, como alterações na liberação de dopamina e na expressão de seus receptores. Conclusão. Futuros estudos precisam explorar mais esta condição através de desenhos experimentais adequados, seguindo o CONSORT, com grupos-controle e resultados validados internacionalmente, na expectativa de controlar os índices de morbi-mortalidade decorrentes deste transtorno alimentar. Unitermos. Obesidade, Dopamina, Receptores DopaminérgicosCitação. Santos AFS, Souza CSV, Oliveira LS, Freitas MFL. Influência da dopamina e seus receptores na gênese da obesidade: revisão sistemática. ABSTRACTIntroduction. Obesity can be considered as a major global public health problem, with alarming numbers worldwide and correlation with several fatal diseases. Environmental factors, as well as various physiological systems are implicated in the cause of the disease. One of these systems, the one of the food reward involving the neurotransmitter dopamine is widely known in the literature as being responsible for motivating the search for natural rewards (food) and artificial rewards (drugs). Objective. To collect data in the literature showing the involvement of dopamine with hyperphagia and obesity. Method. A survey was conducted in three databases (MedLine, Lilacs and Sci-ELO) with descriptors and free terms related to the subject, from May 2013 to March 2014. Results. 391 articles were found. After careful selection, based on exclusion criteria defined for this study, only 17 articles were selected for discussion. In all selected articles, changes in the dopaminergic system in obese participants were observed, including changes in dopamine release and expression of its receptors. Conclusion. Future studies need to further explore this condition through appropriate experimental designs with control groups, following the CONSORT and results validated internationally, to control the morbidity and mortality indices associated to this nutritional disorder.

show abstract

“…Consistent with this hypothesis are the findings of decreased striatal DA D2 receptor levels in the dorsal striatum in extremely obese human subjects (BMI . 45), and animal models of diet-induced obesity that consistently demonstrate decreased ventral striatal/nucleus accumbens DA release and DA D2 receptor levels (13)(14)(15)(16)(17)(18). The development of compulsive food ingestion in animals has been related to the development of decreased striatal DA D2 receptor levels in the setting of decreased DA release and elevated reward thresholds (18).…”

Section: Obesity Dopamine and Reward Behaviorsmentioning

confidence: 99%

Obesity, Dopamine, and Reward Behaviors

Kessler

2013

Acta Neuropsychiatr.

View full text Add to dashboard Cite

Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects

Cited by 157 publications

References 20 publications

High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity

High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity

Influence of dopamine and its receptors in the genesis of obesity: systematic review

Obesity, Dopamine, and Reward Behaviors

Contact Info

Product

Resources

About