Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

PPARα agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARα agonist WY 14,643 (30 μmol·kg−1·day−1 for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARα activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.

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Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00216.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. G91-G96 ◽

Cited By ~ 19

Author(s):

Nicolai J. Wewer Albrechtsen ◽

Anders E. Junker ◽

Mette Christensen ◽

Sofie Hædersdal ◽

Flemming Wibrand ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Liver Disease ◽

Amino Acid ◽

Plasma Levels ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Elevated Plasma ◽

Total Amino Acids

Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon’s action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high-performance liquid chromatography, in obese, middle-aged individuals with I) normal glucose tolerance (NGT) and NAFLD, II) T2D and NAFLD, III) T2D without liver disease, and IV) NGT and no liver disease. Elevated levels of total amino acids were observed in participants with NAFLD and NGT compared with NGT controls (1,310 ± 235 µM vs. 937 ± 281 µM, P = 0.03) and in T2D and NAFLD compared with T2D without liver disease (1,354 ± 329 µM vs. 511 ± 235 µM, P < 0.0001). Particularly amino acids with known glucagonotropic effects (e.g., glutamine) were increased. Plasma levels of total amino acids correlated to plasma levels of glucagon also when adjusting for body mass index (BMI), glycated hemoglobin (HbA1c), and cholesterol levels (β = 0.013 ± 0.007, P = 0.024). Elevated plasma levels of total amino acids associate with hyperglucagonemia in NAFLD patients independently of glycemic control, BMI or cholesterol - supporting the potential importance of a “liver-α-cell axis” in which glucagon regulates hepatic amino acid metabolism. Fasting hyperglucagonemia as seen in T2D may therefore represent impaired hepatic glucagon action with increasing amino acids levels. NEW & NOTEWORTHY Hypersecretion of glucagon (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia may depend on hepatic steatosis rather than type 2 diabetes.

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Interactive effects of aging and aerobic capacity on energy metabolism–related metabolites of serum, skeletal muscle, and white adipose tissue

GeroScience ◽

10.1007/s11357-021-00387-1 ◽

2021 ◽

Author(s):

Haihui Zhuang ◽

Sira Karvinen ◽

Timo Törmäkangas ◽

Xiaobo Zhang ◽

Xiaowei Ojanen ◽

...

Keyword(s):

Adipose Tissue ◽

Amino Acid ◽

White Adipose Tissue ◽

Aerobic Capacity ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Disease Risk ◽

Whole Body ◽

Whole Body Metabolism

AbstractAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial β-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.

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Biochemische Aspekte des Aminosäuren-Stoffwechsels bei Psoriasis vulgaris / Biochemical Aspects of Amino Acid Metabolism in Psoriasis vulgaris

Zeitschrift für Naturforschung C ◽

10.1515/znc-1973-7-816 ◽

1973 ◽

Vol 28 (7-8) ◽

pp. 449-451 ◽

Cited By ~ 2

Author(s):

G. Peter ◽

H. Angst ◽

U. Koch

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Free Amino Acids ◽

Free Amino ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Psoriasis Vulgaris ◽

Normal Subjects ◽

Pathological Process

Free and protein-bound amino acids in serum and scales were investigated. In serum the bound amino acids of psoriatics are significantly higher with exception of Pro, Met, Tyr and Phe in contrast to normal subjects. For free amino acids the differences between normal subjects and psoriatics found in serum and scales are not significant. Results are discussed in relation to the single amino acids and the biochemical correlations are outlined which takes the pathological process as a basis.

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The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽

10.3390/cancers11050675 ◽

2019 ◽

Vol 11 (5) ◽

pp. 675 ◽

Cited By ~ 25

Author(s):

Bo-Hyun Choi ◽

Jonathan L. Coloff

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Cancer Therapy ◽

Metabolic Pathways ◽

Essential Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Essential Amino Acids ◽

Redox Status ◽

Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

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Postharvest changes in ammonium, amino acids and enzymes of amino acid metabolism in asparagus spear tips

Journal of the Science of Food and Agriculture ◽

10.1002/jsfa.2740630414 ◽

1993 ◽

Vol 63 (4) ◽

pp. 465-471 ◽

Cited By ~ 36

Author(s):

Paul L. Hurst ◽

Christopher J. Clark

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism

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IDIOPATHIC HYPERGLYCINEMIA: A NEW DISORDER OF AMINO ACID METABOLISM

PEDIATRICS ◽

10.1542/peds.27.4.539 ◽

1961 ◽

Vol 27 (4) ◽

pp. 539-550 ◽

Cited By ~ 1

Author(s):

William L. Nyhan ◽

Margaret Borden ◽

Barton Childs

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Oral Administration ◽

Dietary Intake ◽

Urinary Excretion ◽

Cation Exchange ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Acute Illness ◽

Progressive Decrease

The amino acids of blood and urine have been investigated using chromatography on cation exchange columns in the study of a patient with idiopathic hyperglycinemia. Marked increases in concentrations of glycine, serine, alanine, isoleucine and valine were found in the plasma. These changes were not reflected in increased excretion of these amino acids in the urine (with the exception of glycine). Restriction of the dietary intake of protein resulted in a decrease in the concentrations of glycine and other amino acids in the blood and urine, and there was a concomitant decrease in the frequency and severity of episodes of acute illness. The oral administration of leucine was found to induce a decrease in the levels of a number of amino acids in the patient and in controls. Continued decrease during the 3 hours of observation was noted for serine, isoleucine and valine. A mild but progressive decrease in threonine concentration was observed in the controls, while in the patient the concentration increased after the administration of leucine. Decreased levels at 1½ hours, returning toward the fasting levels at 3 hours, were observed for alanine, taurine and glycine. These apparently normal responses to leucine loads were not mediated through increase in the urinary excretion of the amino acids involved, and the data are interpreted to indicate entry of these amino acids into cells.

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Invasive Techniques to Evaluate Protein and Amino Acid Metabolism: Regional and Whole Body Amino Acid Kinetic Studies

Protein and Amino Acid Metabolism in Cancer Cachexia - Medical Intelligence Unit ◽

10.1007/978-3-662-22346-8_3 ◽

1996 ◽

pp. 33-49

Author(s):

Russell S. Berman

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Kinetic Studies ◽

Whole Body ◽

Invasive Techniques

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Glucose and amino acid metabolism in mice depend mutually on glucagon and insulin receptor signaling

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00410.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. E660-E673 ◽

Cited By ~ 10

Author(s):

Katrine D. Galsgaard ◽

Marie Winther-Sørensen ◽

Jens Pedersen ◽

Sasha A. S. Kjeldsen ◽

Mette M. Rosenkilde ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Insulin Receptor ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Receptor Signaling ◽

Cell Secretion ◽

Glucagon Receptor ◽

Insulin Receptor Signaling ◽

Glucagon And Insulin

Glucagon and insulin are important regulators of blood glucose. The importance of insulin receptor signaling for alpha-cell secretion and of glucagon receptor signaling for beta-cell secretion is widely discussed and of clinical interest. Amino acids are powerful secretagogues for both hormones, and glucagon controls amino acid metabolism through ureagenesis. The role of insulin in amino acid metabolism is less clear. Female C57BL/6JRj mice received an insulin receptor antagonist (IRA) (S961; 30 nmol/kg), a glucagon receptor antagonist (GRA) (25-2648; 100 mg/kg), or both GRA and IRA (GRA + IRA) 3 h before intravenous administration of similar volumes of saline, glucose (0.5 g/kg), or amino acids (1 µmol/g) while anesthetized with isoflurane. IRA caused basal hyperglycemia, hyperinsulinemia, and hyperglucagonemia. Unexpectedly, IRA lowered basal plasma concentrations of amino acids, whereas GRA increased amino acids, lowered glycemia, and increased glucagon but did not influence insulin concentrations. After administration of GRA + IRA, insulin secretion was significantly reduced compared with IRA administration alone. Blood glucose responses to a glucose and amino acid challenge were similar after vehicle and GRA + IRA administration but greater after IRA and lower after GRA. Anesthesia may have influenced the results, which otherwise strongly suggest that both hormones are essential for the maintenance of glucose homeostasis and that the secretion of both is regulated by powerful negative feedback mechanisms. In addition, insulin limits glucagon secretion, while endogenous glucagon stimulates insulin secretion, revealed during lack of insulin autocrine feedback. Finally, glucagon receptor signaling seems to be of greater importance for amino acid metabolism than insulin receptor signaling.

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Metabolic profile of in vitro derived human embryos is not affected by the mode of fertilization

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaaa015 ◽

2020 ◽

Vol 26 (4) ◽

pp. 277-287

Author(s):

Christine Leary ◽

Roger G Sturmey

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Metabolic Profile ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Human Embryos ◽

Embryo Morphology ◽

Male Factor ◽

Triglyceride Content

Abstract The pattern of metabolism by early embryos in vitro has been linked to a range of phenotypes, including viability. However, the extent to which metabolic function of embryos is modified by specific methods used during ART has yet to be fully described. This study has sought to determine if the mode of fertilization used to create embryos affects subsequent embryo metabolism of substrates. A metabolic profile, including consumption of key substrates and the endogenous triglyceride content of individual IVF and ICSI supernumerary embryos, was assessed and compared. Embryo development and quality was also recorded. All embryos were donated at a single clinical IVF center, on Day 5, from 36 patients aged 18–38 years, The data revealed that consumption of glucose and pyruvate, and production of lactate, did not differ between embryos created by IVF or ICSI. Similarly, the mode of insemination did not impact on the triglyceride content of embryos. However, ICSI-derived embryos displayed a more active turnover of amino acids (P = 0.023), compared to IVF embryos. The specific amino acids produced in higher quantities from ICSI compared to IVF embryos were aspartate (P = 0.016), asparagine (P = 0.04), histidine (P = 0.021) and threonine (P = 0.009) while leucine consumption was significantly lower (P = 0.04). However, importantly neither individual nor collective differences in amino acid metabolism were apparent for sibling oocytes subjected to either mode of fertilization. Embryo morphology (the number of top grade embryos) and development (proportion reaching the blastocyst stage) were comparable in patients undergoing IVF and ICSI. In conclusion, the microinjection of spermatozoa into oocytes does not appear to have an impact on subsequent metabolism and viability. Observed differences in amino acid metabolism may be attributed to male factor infertility of the patients rather than the ICSI procedure per se.

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