Chronic dietary supplementation with kynurenic acid, a neuroactive metabolite of tryptophan, decreased body weight without negative influence on densitometry and mandibular bone biomechanical endurance in young rats

Abstract

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan. KYNA naturally occurs in breast milk and its content increases with lactation, indicating the role of neonatal nutrition in general growth with long-term health effects. KYNA is also an antagonist of ionotropic glutamate receptors expressed in bone cells. The aim of this study was to establish the effects of chronic KYNA supplementation on bone homeostasis in young rats, using mandible as a model bone. Female and male newborn Wistar rats were divided into control and KYNA-administered groups until 60 days of age (25x101 mg/L or 25x102 mg/L in drinking water). Hemimandibles were subjected to densitometry, computed tomography analysis and mechanical testing. Rats supplemented with KYNA at both doses showed a decrease in body weight. There were no effects of KYNA administration and mandible histomorphometry. In males, a significant quadratic effect (P < 0.001) was observed in the densitometry of the hemimandible, where BMD increased in the group supplemented with 2.5x101 mg/L of KYNA. Analysis of mechanical tests data showed that when fracture forces were corrected for bone geometry and rats body weight the improvement of bone material properties was observed in male and female rats supplemented with lower dose of KYNA. This study showed that chronic supplementation with KYNA may limit weight gain in the young, without adversely affecting the development of the skeleton.

The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab (Tachypleus tridentatus) on Obesity, Hyperlipidemia, and Gut Microbiota in High‐Fat Diet‐Fed Mice

“…The i.g. of 5 mg/kg/day KA (KAH) for 8 weeks did not cause any obvious side effects in general appearance of HFD mice, which is consistent with two previous reports [ 58 , 59 ]. Dietary supplementation of KA (250 mg/L in drinking water) did not induce toxic effects in normal adult rats (continuous supplementation for 21 days) or normal adult mice (continuous supplementation for 14 days) [ 59 ].…”

“…Dietary supplementation of KA (250 mg/L in drinking water) did not induce toxic effects in normal adult rats (continuous supplementation for 21 days) or normal adult mice (continuous supplementation for 14 days) [ 59 ]. Chronic dietary supplementation with KA (25 mg/L or 250 mg/L in drinking water) for 40 days decreased body weight but without negative influence on the development of the skeleton in young normal rats [ 58 ]. Importantly, several products for the daily human diet were also found to contain KA, including broccoli, potato, honeybee products, tea, and coffee [ 48 , 60 ].…”

β-Hydroxy-β-Methylbutyrate (HMB) Supplementation Prevents Bone Loss during Pregnancy—Novel Evidence from a Spiny Mouse (Acomys cahirinus) Model

“…Reconstruction was performed using DatosX 2.0 software (GE Sensing & Inspection Technologies GmbH, Wunstorf, Germany) and 16-bit, grey-level 3D images were generated. Image analysis was performed using VG Studio Max 2.0 (Volume Graphics GmbH, Heidelberg, Germany) and ImageJ (U.S. National Institutes of Health, Bethesda, MA, USA) and Avizo 9 (FEI, Hillsboro, OR, USA) software [ 76 ].…”

Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

“…KYNA activates the orphan G-protein receptor 35 (GPR35) expressed in the glia and neurons of the hippocampus, which inhibits the adenylate cyclase and depresses excitability and synaptic transmission in the hippocampus [23]. In addition, KYNA decreased body weight without negative influence on densitometry and mandibular bone [24].…”