Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions

Lafourcade, Mathieu; Larrieu, Thomas; Mato, Susana; Duffaud, Anaïs; Sepers, Marja D.; Matías, Isabelle; Smedt-Peyrusse, Véronique de; Labrousse, Virginie F; Brétillon, Lionel; Matute, Carlos; Rodrı́guez-Puertas, Rafael; Layé, Sophie; Manzoni, Olivier J.

doi:10.1038/nn.2736

Cited by 276 publications

(280 citation statements)

References 50 publications

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“…The contribution of nutrients themselves and/or their metabolites in this process should be considered too. For instance, dietary fat-derived endocannabinoids are major components of the gut-brain axis and can engender synaptic alterations in the brain (Crosby et al, 2011;Lafourcade et al, 2011;Bermudez-Silva et al, 2012). On the other hand, it seems that stress-related signals are not involved in diet-induced hypothalamic plasticity because familiar conditions, like reexposure to HFD, still produced upregulation of the plasticity marker PSA, whereas food novelty was not sufficient to induce this response.…”

Section: Discussionmentioning

confidence: 99%

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

et al. 2012

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Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticitydriven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.

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Section: Discussionmentioning

confidence: 99%

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

et al. 2012

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“…Given the epidemiological and clinical data linking n −3 PUFAs deficiency with mood disorders (Parker et al, 2006), autoimmune diseases (Fernandes et al, 2008) and abnormal synaptic plasticity (Lafourcade et al, 2011), it is likely that n −3 PUFA may play a pivotal role in treating autoimmune disease and co-morbid mood disorders. Our data confirmed that 6 month old BAFF Tg mice display abnormal hippocampal progenitor cell proliferation (Crupi et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

n−3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice

Crupi

Cambiaghi

Deckelbaum

et al. 2012

Preventive Medicine

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Objective. Autoimmune-prone B-cell activating factor transgenic mice, a mouse model of systemic lupus erythematosus and Sjögren's syndrome exhibit neuroinflammation, anxiety-like phenotype, deficit in adult hippocampal neurogenesis and impaired neurogenesis-dependent and neurogenesis-independent dentate gyrus long-term potentiation. Given that n−3 polyunsaturated fatty acids regulate hippocampal plasticity and inflammatory responses, we investigated whether n−3 polyunsaturated fatty acids-enriched diet might prevent age-dependent hippocampal changes in B-cell activating factor transgenic mice.Methods. B-cell activating factor transgenic mice were fed for 12 weeks with either n−3 polyunsaturated fatty acids-enriched or control diet and we tested the effect of this dietary supplementation on hippocampal inflammation, progenitor cell proliferation and neurogenesis-dependent and neurogenesis-independent long-term potentiation.Results. Dietary supplementation with n−-3 polyunsaturated fatty acids significantly decreased hippocampal microglial activation and increased the density of bromodeoxyuridine and doublecortin-positive newly-formed cells in the subventricular zone of hippocampus. Furthermore, B-cell activating factor transgenic mice fed with n-3 polyunsaturated fatty acids-enriched diet displayed normal long-term potentiation at the medial perforant pathway/dentate gyrus connections.Conclusions. The results indicate that n-3 fatty acids prevent neuroinflammation and deficits of hippocampal plasticity in B-cell activating factor transgenic mice and suggest that increased n-3 fatty acids intake might represent a potential therapeutic option to prevent neuropsychiatric symptoms associated with autoimmune diseases.

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“…For instance, DHA is essential for normal development and function of the brain (30). Deficiency of DHA in the nervous system impairs synaptic transmission (31) and DHA supplementation may be protective against neurodegenerative diseases and psychiatric disorders (32,33).…”

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confidence: 99%

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Hoshi

Tian

et al. 2013

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

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Large-conductance Ca 2+ -and voltage-activated K + (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.K Ca 1.1 | fish oil | lipids

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Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions

Cited by 276 publications

References 50 publications

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

n−3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

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