A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency

Téllez, Luis A.; Medina, Sara; Han, Wenfei; Ferreira, Jozélia Gomes Pacheco; Licona-Limón, Paula; Ren, Xueying; Lam, Tu Kiet T.; Schwartz, Gary J.; Araújo, Ivan E. de

doi:10.1126/science.1239275

Cited by 268 publications

(348 citation statements)

References 34 publications

(36 reference statements)

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“…2001; Fu et al 2003; Tellez et al. 2013). In support of this idea, OEA activated vagal afferent neurons in cultures of nodose ganglia neurons (Wang et al.…”

Section: Discussionmentioning

confidence: 99%

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

et al. 2018

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The endogenous peroxisome proliferator‐activated receptor alpha (PPAR‐α) agonist Oleoylethanolamide (OEA) inhibits eating in rodents, mainly by delaying the onset of meals. The underlying mechanisms of OEA‐induced anorexia, however, remain unclear. Animals treated with high OEA doses were shown to display signs of discomfort and impaired locomotion. Therefore, we first examined whether the impaired locomotion may contribute to OEA's anorectic effect. Second, it is controversial whether abdominal vagal afferents are necessary for OEA's anorectic effect. Thus, we explored alternative peripheral neural pathways mediating IP OEA's anorectic effect by performing a celiac‐superior mesenteric ganglionectomy (CGX) or a subdiaphragmatic vagal deafferentation (SDA) alone or in combination. Exogenously administered OEA at a commonly used dose (10 mg/kg BW, IP) concurrently reduced food intake and compromised locomotor activity. Attempts to dissociate both phenomena using the dopamine D2/D3 receptor agonist Quinpirole (1 mg/kg BW, SC) failed because Quinpirole antagonized both, OEA‐induced locomotor impairment and delay in eating onset. CGX attenuated the prolongation of the latency to eat by IP OEA, but neither SDA nor CGX prevented IP OEA‐induced locomotor impairment. Our results indicate that IP OEA's anorectic effect may be secondary to impaired locomotion rather than due to physiological satiety. They further confirm that vagal afferents do not mediate exogenous OEA's anorectic effects, but suggest a role for spinal afferents in addition to an alternative, nonneuronal signaling route.

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“…2001; Fu et al 2003; Tellez et al. 2013). In support of this idea, OEA activated vagal afferent neurons in cultures of nodose ganglia neurons (Wang et al.…”

Section: Discussionmentioning

confidence: 99%

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

et al. 2018

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“…Interestingly, we also found that OEA decreased neuronal activity within the nucleus accumbens, as suggested by the low expression of c-Fos in both HDC-KO and WT mice. Although in this context we did not investigate this aspect further, it is interesting that OEA restores gut-stimulated dopamine release in the striatum of high-fat-fed rats increasing the reward value of unpalatable, yet healthier food (38). As brain histamine signaling in the PVN seems to be involved in the acute effects of OEA on food consumption, we expected OEA to increase brain histamine release.…”

Section: Discussionmentioning

confidence: 99%

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

Provensi

Coccurello

Umehara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

108

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Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not known whether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker α-fluoromethylhistidine (α-FMH). α-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H 3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA.histamine receptors | behavioral satiety sequence | BSS | paraventricular hypothalamic nuclei | PVN E ating behavior is regulated by central neurotransmitter systems and peripheral stimuli that interact to change the behavioral state and concur to alter homeostatic aspects of appetite and energy expenditure. The fatty acid amide oleoylethanolamide (OEA) is released by the small intestine in a stimulus-dependent manner and suppresses food intake by activating peroxisome proliferator-activated receptor-α (PPAR-α) (1). Systemic administration of OEA induces c-Fos mRNA expression through the vagus nerve to the nucleus of the solitary tract (NST), supraoptic nuclei (SON), and paraventricular hypothalamic nuclei (PVN) and increases the expression of oxytocin (2, 3), which is involved in the central coordination of homeostatic signals and feeding behavior (4). However, it is not known whether OEA recruits other neurotransmitter systems in the brain to reduce food intake. Histaminergic neurons are clustered in the hypothalamic tuberomammillary nuclei (TMN). They send projections organized in functionally distinct circuits impinging on different brain regions (5), and their firing frequency changes according to the behavioral state (6). Brain histamin...

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“…In addition, in obese patients, obesity might be exacerbated by a reduction in the ability of post-ingestive nutrients to activate dopamine signalling. This has been suggested by the link between gut-derived signals and dopamine in high-fat fed mice [61]. Finally, decoupling of taste from nutritional content may also be involved in behavioural and metabolic disturbances.…”

Section: Implications For Obesity and Human Feeding Behaviourmentioning

confidence: 99%

“…This effect was mediated by reduced release of the gut-derived satiety factor, oleoylethanolamine (OEA) [61]. Thus, one potential mechanism underlying obesity might be the inability of postingestive signals such as OEA to activate dopamine signalling and induce satiety.…”

Section: Post-ingestive Infusionsmentioning

confidence: 99%

“…In addition, specific components of a pathway involved in nutrient-sensing may be targeted. For example, the pathway linking fat intake and sensing in the gut to increased dopamine efflux has been determined by blocking components of this signalling cascade [61]. Finally, the precise role for dopamine in any behavioural or neurochemical response has been tested by using antagonists to dopamine receptors allowing the specific receptor subtype involved to be resolved [57].…”

Section: Pharmacological Manipulationsmentioning

confidence: 99%

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The role of dopamine in the pursuit of nutritional value

McCutcheon

2015

Physiology & Behavior

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Acquiring enough food to meet energy expenditure is fundamental for all organisms. Thus, mechanisms have evolved to allow foods with high nutritional value to be readily detected, consumed, and remembered. Although taste is often involved in these processes, there is a wealth of evidence supporting the existence of taste-independent nutrient sensing. In particular, post-ingestive mechanisms arising from the arrival of nutrients in the gut are able to drive food intake and behavioural conditioning. The physiological mechanisms underlying these effects are complex but are believed to converge on mesolimbic dopamine signalling to translate post-ingestive sensing of nutrients into reward and reinforcement value. Discerning the role of nutrition is often difficult because food stimulates sensory systems and post-ingestive pathways in concert. Thus, in this mini-review, I discuss the various methods that may be used to study post-ingestive processes in isolation including sham-feeding, nonnutritive sweeteners, post-ingestive infusions, and pharmacological and genetic methods. Using this structure, I present the evidence that dopamine is sensitive to nutritional value of certain foods and examine how this affects learning about food, the role of taste, and the implications for human obesity.

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A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency

Cited by 268 publications

References 34 publications

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

The role of dopamine in the pursuit of nutritional value

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