Dietary Supplementation with α-Ketoglutarate Activates mTOR Signaling and Enhances Energy Status in Skeletal Muscle of Lipopolysaccharide-Challenged Piglets

Wang, Lei; Yi, Dan; Hou, Yongqing; Ding, Biao; Li, Kang; Li, Baocheng; Zhu, Huiling; Liu, Yulan; Wu, Guoyao

doi:10.3945/jn.116.236000

Cited by 34 publications

(36 citation statements)

References 57 publications

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“…The AKG doses were selected based on the combination of several articles (Chen et al, 2017;Wang et al, 2016). The three treatment groups were the low-protein diet supplemented with 0.5% (LP + 0.5%A), 1.0% (LP + 0.5%A) and 1.5% AKG (LP + 0.5%A).…”

Section: Experimental Dietsmentioning

confidence: 99%

“…Furthermore, Wang et al (2016) found that AKG has been added to the diet of animals to alleviate the phenomenon that IGF-1 content decreases in the blood caused by LPS stimulation. LP, low protein; LP + 0.5%A, low-protein diet supplemented with 0.5% AKG; LP + 1.0%A, low-protein diet supplemented with 1.0% AKG; LP + 1.5%A, low-protein diet supplemented with 1.5% AKG.…”

Section: Consequently Akg Promotes N Depositions In Cells Throughoutmentioning

confidence: 99%

“…The three treatment groups were the low-protein diet supplemented with 0.5% (LP + 0.5%A), 1.0% (LP + 0.5%A) and 1.5% AKG (LP + 0.5%A). The AKG doses were selected based on the combination of several articles (Chen et al, 2017;Wang et al, 2016). As optimized by the National Research Council (NRC, 2012) to meet nutrient requirements of piglets (11-25 kg), diets were formulated according to the net energy system (Table 1).…”

Section: Experimental Dietsmentioning

confidence: 99%

“…(2017) found that AKG is absorbed by the body, then enters the tricarboxylic acid cycle (TCA) for a particular bodily function and increases glucose levels in serum. Furthermore, Wang et al (2016) found that AKG has been added to the diet of animals to alleviate the phenomenon that IGF-1 content decreases in the blood caused by LPS stimulation. IGF-1 is a polypeptide that is secreted by liver cells after growth hormone binds to the growth hormone receptor on the surface of hepatocytes.…”

Section: Consequently Akg Promotes N Depositions In Cells Throughoutmentioning

confidence: 99%

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Effects of low‐protein diet supplementation with alpha‐ketoglutarate on growth performance, nitrogen metabolism and mTOR signalling pathway of skeletal muscle in piglets

Zhao

Guo

Sun

2019

Animal Physiology Nutrition

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Excessive protein levels in diets result in incomplete digestion of nitrogenous nutrients that are excreted from the body, causing environment pollution. Alpha‐ketoglutarate (AKG) has been reported to decrease dietary protein levels, promote intestinal health in piglets and reduce environmental pollution. However, the underlying mechanisms of AKG are largely unknown. The objective of this study was to determine the effects of low‐protein diet supplementation of AKG on the growth performance, nitrogen metabolism, relative expression of amino acid transporter genes and mTOR signalling pathway of skeletal muscle in piglets. Forty‐eight piglets with an initial weight of 11.53 ± 0.04 kg were randomly divided into four groups. Each group had four replicates, and each replicate had three pigs. A low‐protein (LP) diet (crude protein was 14.96%) served as the control without AKG, while 0.5%, 1.0% and 1.5% AKG were added to the LP diet for the other experimental groups. The trial period lasted for 28 days. Compared with the LP group, the LP + 1.0%A and LP + 1.5%A groups increased the growth performance (p < .05);increased the mRNA levels of amino acid transporters in the duodenum, anterior jejunum and posterior jejunum (p < .05); and reduced faecal nitrogen and urine nitrogen emissions (p < .05). They also showed greater mRNA levels and phosphorylated protein levels for S6 kinase beta (S6K) (p < .05), mammalian target of rapamycin (mTOR) (p < .05) and 4E‐binding protein 1 (4EBP1) (p < .05) in skeletal muscle. An LP diet supplemented with AKG activated the mTOR signalling and promoted the ability of the small intestine to absorb protein, thereby increasing protein deposition. Taken together, an LP diet supplemented with AKG provides a theoretical basis for the promotion and application of AKG in piglet production.

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Section: Experimental Dietsmentioning

confidence: 99%

Section: Consequently Akg Promotes N Depositions In Cells Throughoutmentioning

confidence: 99%

Section: Experimental Dietsmentioning

confidence: 99%

Section: Consequently Akg Promotes N Depositions In Cells Throughoutmentioning

confidence: 99%

See 2 more Smart Citations

Effects of low‐protein diet supplementation with alpha‐ketoglutarate on growth performance, nitrogen metabolism and mTOR signalling pathway of skeletal muscle in piglets

Zhao

Guo

Sun

2019

Animal Physiology Nutrition

View full text Add to dashboard Cite

show abstract

“…Concentrations of biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), blood urea nitrogen (BUN), total bilirubin (TBIL), cholesterol (CHOL) and creatinine in plasma were measured with corresponding kits using a Hitachi 7060 Automatic Biochemical Analyzer (Hitachi, Japan) (23). D-xylose in plasma was determined as described by Hou et al (17).…”

Section: General Study Protocolmentioning

confidence: 99%

Establishment of a recombinant i Escherichia coli i -induced piglet diarrhea model

et al. 2018

Front Biosci

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Enterotoxigenic strains induce human and animal intestinal dysfunction and injury, and cause diarrhea in weanling pigs. A recombinant strain LMG194-STa which expressed single toxin STa of ETEC was constructed by directly inserting the STa gene of ETEC into the expression vector pBAD202 and then transferring the recombinant plasmid pBAD-STa into the LMG19 host strain. Diarrhea and intestinal injury in piglets were induced by oral administration of recombinant strain LMG194-Sta., the recombinant strain LMG194-Sta had the same toxicity to the IPEC cell as wild type strain K88, and higher toxicity than the host strain LMG194. , LMG194-STa caused severe diarrhea in piglets as K88, the diarrhea rate of LMG194-STa and K88 groups was higher than that in the LMG194 and control groups. Both K88 and LMG194-STa induced intestinal inflammation, injury, and atrophy, while adversely affecting the expression of genes for cytokines, transporters and ion channels, and nutrient metabolism. Thus, we established a porcine model of recombinant strain LMG194-STa-induced diarrhea for future nutritional and mechanistic studies of intestinal dysfunction.

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Dimethyl-2-oxoglutarate improves redox balance and mitochondrial function in muscle pericytes of individuals with diabetes mellitus

et al. 2020

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Aims/hypothesis Treatment of vascular complications of diabetes remains inadequate. We reported that muscle pericytes (MPs) from limb muscles of vascular patients with diabetes mellitus display elevated levels of oxidative stress causing a dysfunctional phenotype. Here, we investigated whether treatment with dimethyl-2-oxoglutarate (DM-2OG), a tricarboxylic acid cycle metabolite with antioxidant properties, can restore a healthy metabolic and functional phenotype. Methods MPs were isolated from limb muscles of diabetes patients with vascular disease (D-MPs) and from non-diabetic control participants (ND-MPs). Metabolic status was assessed in untreated and DM-2OG-treated (1 mmol/l) cells using an extracellular flux analyser and anion-exchange chromatography–mass spectrometry (IC-MS/MS). Redox status was measured using commercial kits and IC-MS/MS, with antioxidant and metabolic enzyme expression assessed by quantitative RT-PCR and western blotting. Myogenic differentiation and proliferation and pericyte–endothelial interaction were assessed as functional readouts. Results D-MPs showed mitochondrial dysfunction, suppressed glycolytic activity and reduced reactive oxygen species-buffering capacity, but no suppression of antioxidant systems when compared with ND-MP controls. DM-2OG supplementation improved redox balance and mitochondrial function, without affecting glycolysis or antioxidant systems. Nonetheless, this was not enough for treated D-MPs to regain the level of proliferation and myogenic differentiation of ND-MPs. Interestingly, DM-2OG exerted a positive effect on pericyte–endothelial cell interaction in the co-culture angiogenesis assay, independent of the diabetic status. Conclusions/interpretation These novel findings support the concept of using DM-2OG supplementation to improve pericyte redox balance and mitochondrial function, while concurrently allowing for enhanced pericyte–endothelial crosstalk. Such effects may help to prevent or slow down vasculopathy in skeletal muscles of people with diabetes.

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Dietary Supplementation with α-Ketoglutarate Activates mTOR Signaling and Enhances Energy Status in Skeletal Muscle of Lipopolysaccharide-Challenged Piglets

Abstract: Dietary AKG supplementation activated mTOR signaling, inhibited ACC-β, and improved energy status in skeletal muscle of LPS-challenged piglets. These results provide a biochemical basis for the use of AKG to enhance piglet growth under inflammatory or practical postweaning conditions.

Cited by 34 publications

References 57 publications

Effects of low‐protein diet supplementation with alpha‐ketoglutarate on growth performance, nitrogen metabolism and mTOR signalling pathway of skeletal muscle in piglets

Effects of low‐protein diet supplementation with alpha‐ketoglutarate on growth performance, nitrogen metabolism and mTOR signalling pathway of skeletal muscle in piglets

Establishment of a recombinant i Escherichia coli i -induced piglet diarrhea model

Dimethyl-2-oxoglutarate improves redox balance and mitochondrial function in muscle pericytes of individuals with diabetes mellitus

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