Aspartic acid supplementation ameliorates symptoms of diabetic kidney disease in mice

Abstract

Diabetic kidney disease (DKD) is among the most common and serious complications of both type 1 and type 2 diabetes. In this study, we used KK/Ta‐Ins2Akita (KK‐Akita) mice as a model of DKD and KK/Ta (KK) mice as controls to identify novel factors related to the development/progression of DKD. Capillary electrophoresis coupled with mass spectrometry analysis revealed that circulating Asp (l‐aspartic acid) levels in diabetic KK‐Akita mice tend to be lower than those in control KK mice. Therefore, we evaluated the effect of Asp supplementation to prevent the progression of DKD in KK‐Akita mice. Mice were divided into three groups: (a) untreated KK mice (Control group), (b) untreated KK‐Akita mice (DKD group), and (c) treated (double‐volume Asp diet) KK‐Akita mice (Tx group). Kidney sections were stained with fluorescein isothiocyanate‐labeled lectins, wheat germ agglutinin (WGA), and anti‐endothelial nitric oxide synthase (eNOS) antibody for evaluation of endothelial surface layer (ESL) and NO synthesis. The mesangial area and glomerular size in the DKD group were significantly larger than those in the Control group; however, there was no significant difference in those between the DKD and Tx groups. Albuminuria, the ratio of foot process effacement, and thickness of glomerular basement membrane in the Tx group were significantly lower than those in the DKD group. Furthermore, the expression levels of glomerular WGA and microvascular eNOS in the Tx group improved significantly and approached the level in the Control group. In conclusion, the improvement of albuminuria in the Tx group may be caused by the reduction of oxidative stress in the kidneys, which may lead to the subsequent improvement of glomerular ESL.

Analysis of Fatty Acids, Amino Acids and Volatile Profile of Apple By-Products by Gas Chromatography-Mass Spectrometry

“…In the present study, Asp was the most abundant amino acid identified in all samples, ranging from 28.10 to 63.57 mg/100 g. Recently, it has been shown that Asp could be successfully used in the prevention of diabetic kidney mice disease, highlighting the importance of this non-essential amino acid in kidney oxidative stress reduction [ 50 ]. Asp was identified in high amounts also by Zhang et al [ 51 ] at the maturity stage of Honeycrisp apples, but also as the second most abundant amino acid in apple Malus domestica Borkh cv.…”

“…The color characteristics of the final biscuits were analyzed according to our recent work [ 50 ], by using an NH 300 portable colorimeter (Shenzhen ThreeNH Technology Co., Ltd., Shenzhen, China), having a color system based on CIE L* (luminosity), a* (red/green coordinate), b* (yellow/blue coordinate) color. The colorimeter was previously calibrated using its own black and white calibration system.…”

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

“…Recently, a study demonstrated that L-aspartate supplementation could ameliorate diabetic kidney disease in mice. 47 In mechanism, a latest study done by Jiang et al revealed that L-aspartate can directly interact with phosphorylated LKB1 leading to an activation of LKB1-AMPK axis in cells. 37 Consistently, our study also found L-aspartate treatment activated LKB1-AMPK axis in hepatocyte and intestinal cells, enhanced lipid oxidation and inhibited oxidative stress and its induced cell injury, thus ameliorating MAFLD.…”

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

“…L-aspartate is a non-essential amino acid and involved in treatment for acute and chronic liver hepatitis and cirrhosis treatment in the clinic by regulating nitrogen metabolism, nucleic acid synthesis and the Kreb's cycle (Hou et al, 2017;Leng et al, 2014). Recently, a study reported that L-aspartate supplementation ameliorated diabetic kidney disease in mice (Ichikawa et al, 2020). Moreover, Jiang et al revealed that L-aspartate directly interacted with phosphorylated LKB1 and activated the LKB1-AMPK axis in cells (Deng et al, 2020).…”