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

Giessen, Elsmarieke van de; Fleur, Susanne E. la; Eggels, Leslie; Bruin, Kora de; Brink, Wim van den; Booij, Jan

doi:10.1038/ijo.2012.128

Cited by 64 publications

(38 citation statements)

References 19 publications

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“…Here, we investigated the hypothesis that diet-induced obesity causes physical inactivity via deficits in striatal DA transmission. Consistent with previous work, we found that chronic high-fat diet decreased striatal D2R binding (Hajnal et al, 2008; Huang et al, 2006; Narayanaswami et al, 2013; van de Giessen et al, 2012; van de Giessen et al, 2013). We also observed a deficit in motor-related firing of striatal neurons in obese mice.…”

Section: Discussionsupporting

confidence: 92%

“…Finally, factors such as sleep duration (Wiers et al, 2016) and caffeine intake (Volkow et al, 2015) can also affect D2R binding, and are not reported or controlled in most clinical studies. These sources of variance can be mitigated in animal studies, which paint a consistent picture of reductions in D2R mRNA (Mathes et al, 2010; Zhang et al, 2015), protein (Adams et al, 2015; Johnson and Kenny, 2010), and receptor binding (Hajnal et al, 2008; Huang et al, 2006; Narayanaswami et al, 2013; van de Giessen et al, 2012; van de Giessen et al, 2013) in obese rodents. Our work extends this body of literature by reporting that other aspects of DA signaling remain unchanged in obese mice, even those with reductions in D2Rs.…”

Section: Discussionmentioning

confidence: 99%

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Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity

et al. 2017

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Summary Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, while restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, while mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity

et al. 2017

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“…Following diet exposure, both DIO-prone and DIO-resistant rats displayed cross-sensitization to amphetamine and down-regulation of striatal dopamine D2 receptors (D2Rs). Thus, while enhanced food cue reactivity precedes obesity and may confer vulnerability to overeating and diet-induced weight gain, other adaptations in dopamine function may occur as a direct consequence of palatable diet consumption, regardless of weight gain [36]. …”

Section: Metabolic Control Of Food Cue Reactivity In the Nucleus Accumentioning

confidence: 99%

Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior

Burke

2016

Current Opinion in Behavioral Sciences

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Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning.

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“…Of the opioid-expressing neurons, enkephalin (ENK) neurons are of specific interest as they express dopamine D2 receptors and have been linked to high-fat feeding, i.e., Acb enkephalin gene expression is affected by consumption of the highly palatable Ensure drink (17), which contains fat and sugar, and striatal D2 receptor availability is correlated with high-fat intake (18). Moreover, enkephalin binds to mu-opioid receptors and local Acb administration of the mu-opioid receptor agonist DAMGO specifically increases intake of high-fat foods (19).…”

mentioning

confidence: 99%

Neuropeptide Y Activity in the Nucleus Accumbens Modulates Feeding Behavior and Neuronal Activity

Heuvel

Furman

Gumbs

et al. 2015

Biological Psychiatry

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Background Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb. Methods First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-Acb NPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb. Results In rats on the free-choice, high-fat, high-sugar diet, intra-Acb NPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-Acb NPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acb enkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb. Conclusions NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-Acb NPY-induced fat intake.

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

Cited by 64 publications

References 19 publications

Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity

Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity

Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior

Neuropeptide Y Activity in the Nucleus Accumbens Modulates Feeding Behavior and Neuronal Activity

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