Dysfunctional d-aspartate metabolism in BTBR mouse model of idiopathic autism

Abstract

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Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis

“…This novel finding was quite inconsistent with the traditional theory that L-aspartate being mainly produced in the liver. 42,43 In addition to L-aspartate, we also observed that A. muciniphila treatment elevated the levels of SCFAs in liver including propionate and acetate, which have beneficial metabolic effects in curbing obesity and MAFLD. 44,45 The elevated metabolites may separately or together underlie the therapeutic effect of A. muciniphila in MAFLD.…”

Gut Akkermansia muciniphila ameliorates non-alcoholic fatty liver disease by L-aspartate via interaction with liver

“…Furthermore, A. muciniphila treatment increased the expression level of the L-aspartate transporter in the ileum and liver, suggesting that A. muciniphila plays an important role in regulating L-aspartate transportation. This novel finding was quite unfamiliar with the traditional theory of L-aspartate being mainly produced in the liver (Nuzzo et al, 2020;Leng et al, 2014). Moreover, a negative correlation was observed between the L-aspartate level and the hepatic TG level, suggesting that A. muciniphila ameliorated NAFLD in mice may be closely related to the increased levels of L-aspartate.…”

New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and Endocrine System Physiology: From Preclinical Observations to Clinical Applications

“…Given that NMDARs regulate neuron development, maturation, and migration [77][78][79][80], we argue that D-Asp is a candidate signaling molecule involved in neurodevelopmental processes. Notably, a recent study revealed a severe reduction of Ddo gene expression accompanied by an increase of D-Asp levels in the brain of BTBR mice, which is a widely accredited animal model of idiopathic autism [14]. Furthermore, in an attempt to understand the biological meaning of the elevated levels of D-Asp during brain development, a Ddo knock-in mouse model with complete depletion of this D-amino acid has been generated [22].…”

“…Conversely, the concentration of this amino acid is low in the endocrine glands during gestational phases and progressively increases during postnatal life [12]. Pharmacologically, D-Asp can modulate glutamatergic NMDAR-mediated transmission and functions, and dysregulation of its metabolism occurs in the brain of schizophrenia patients and in an animal model of autism spectrum disorders [13][14][15].…”