The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

Andersen, Naja Kirstine; Tatara, Marcin R.; Krupski, Witold; Majcher, Piotr; Harrison, Adrian P.

doi:10.1111/j.1439-0396.2007.00742.x

Cited by 16 publications

(18 citation statements)

References 40 publications

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“…Alpha-ketoglutarate is formed during the Krebs cycle and can also be synthesized by certain anaerobic bacteria, including several species of Bacteriodes (Allison et al 1979). Increased levels have been associated with a number of benefits including: increased bone growth as measured by the length of the 6th rib in pigs (Andersen et al 2008), decreased cholesterol levels in rats (Radzki et al 2009), protection of gut mucosa and kidney function (Dabek et al 2005), and possible prevention of inappropriate muscle catabolism during times of stress, such as surgery, injury and illness (Wiren et al 2002). As with several other observed metabolite differences, the increase in alpha ketoglutarate is likely due to changes in the composition of the intestinal microbe population.…”

Section: Discussionmentioning

confidence: 99%

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

et al. 2009

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Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health.

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Section: Discussionmentioning

confidence: 99%

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

et al. 2009

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“…Early treatment with α‐ketoglutarate at a daily dosage of 0.1 g (kg body weight) −1 induced positive long‐term effects on the skeletal system and increased vBMD and the mechanical strength of femur and ribs (Harrison et al 2004; Tatara et al 2007 c ). In newborn pigs, 3 weeks of neonatal administration with AKG improved bone strength, and this effect was associated with an elevated plasma concentration of 17β‐oestradiol (Andersen et al 2008). Similarly to the increase of serum concentration of GH and IGF‐1 in 21‐day‐old lambs in the present study, AKG elevated plasma 17β‐oestradiol levels in pigs only during the period of administration.…”

Section: Discussionmentioning

confidence: 99%

“…Maternal administration of HMB had long‐term effects on bone tissue owing to improved somatotrophic axis function and increased volumetric bone mineral density, as well as geometrical and mechanical properties of the femur in the offspring (Tatara et al 2007 b ). In other studies on pigs, 3 weeks of neonatal administration of α‐ketoglutarate (AKG) induced positive long‐term effects on skeletal system properties that were investigated at the slaughter age (Andersen et al 2008). Similar results were obtained in sheep given AKG during the first 2 weeks of life.…”

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confidence: 99%

Neonatal programming of skeletal development in sheep is mediated by somatotrophic axis function

Tatara¹

2008

Experimental Physiology

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Nutritional and metabolic exposure during critical periods of prenatal and neonatal development in animals and humans may induce long-term effects on health status in later life. The aim of this study was to investigate the effects of neonatal treatment with β-hydroxy-β-methylbutyrate (HMB) during the first 3 weeks of life on programming of skeletal development in sheep. The study was performed on 12 male sheep divided into two groups. While the control group was treated with placebo, the lambs in the HMB group received the calcium salt of β-hydroxy-β-methylbutyrate at a daily dose of 0.1 g (kg body weight) −1 . The assessment of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and biochemical bone turnover markers in serum was performed in 21-and 130-day-old animals. Post mortem, volumetric bone mineral density, morphological and mechanical properties were determined in femur and lumbar vertebrae. Neonatal treatment with HMB increased serum concentrations of bone-specific alkaline phosphatase, osteocalcin, GH and IGF-1 in 21-day-old lambs by 125.2, 93.8, 71.8 and 70.9%, respectively (P ≤ 0.05). The C-terminal telopeptide of type I collagen (CTX) concentration was increased in 130-day-old animals from the HMB group by 33.1% (P = 0.03). Furthermore, HMB administration improved bone weight, volumetric bone mineral density and bone morphological and mechanical properties of femur and lumbar spine. In conclusion, this study showed long-term beneficial effects of neonatal treatment with HMB on programming of peripheral and axial skeleton properties that were mediated by a transient improvement of somatotrophic axis function and acceleration of bone metabolism.

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“…We demonstrated that the LP + 1.0%A and LP + 1.5%A groups show greater mRNA levels for CAT1, EAAC1 increasing the growth performance of piglets. AKG has been reported to promote protein synthesis by increasing the phosphorylation of the mTOR complex, S6K1 and 4E-BP1 (Andersen, Tatara, Krupski, Majcher, & Harrison, 2008;Chen et al, 2018).…”

Section: Consequently Akg Promotes N Depositions In Cells Throughoutmentioning

confidence: 99%

“…AKG has been reported to promote protein synthesis by increasing the phosphorylation of the mTOR complex, S6K1 and 4E-BP1(Andersen, Tatara, Krupski, Majcher, & Harrison, 2008;Chen et al, 2018).Recently, it has been reported that LP diet supplementationwith AKG can increase the phosphorylation of both downstream effectors of the mTOR signalling pathway in skeletal muscle of piglets, moreover, inhibiting proteolysis via the Akt/mTOR pathway(Cai et al, 2016). AKG is a crucial intermediate in the TCA cycle and can be used to produce ATP and amino acids in animal tissues and intestine.…”

mentioning

confidence: 99%

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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The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

Cited by 16 publications

References 40 publications

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Neonatal programming of skeletal development in sheep is mediated by somatotrophic axis function

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

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