Branched-chain amino acids regulate hyaluronan synthesis and PPARα expression in the skin

2021 ◽  
Author(s):  
Takumi Yamane ◽  
Yasuyuki Kitaura ◽  
Ken Iwatsuki ◽  
Yoshiharu Shimomura ◽  
Yuichi Oishi
Keyword(s):  
Branched Chain Amino Acids ◽  
Peroxisome Proliferator ◽  
Keto Acid ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Branched Chain Amino Acid ◽  
Key Enzyme ◽  
In The Wild ◽  
Branched Chain ◽  
Gene Expression Levels

Abstract We examined the effects of deletion of branched-chain α-keto acid dehydrogenase kinase (BDK), a key enzyme in branched-chain amino acid catabolism, on hyaluronan synthesis in mice. The skin levels of hyaluronan and the gene expression levels of hyaluronan synthase (Has)2, Has3 and peroxisome proliferator-activated receptor-α (PPARα) were significantly lower in the BDK-knockout group than in the wild type group.

Transamination of branched-chain keto acids by isolated perfused rat kidney.

1978 ◽  
Vol 235 (1) ◽  
pp. E47
Author(s):  
W E Mitch ◽  
W Chan
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Branched Chain Amino Acids ◽  
Keto Acid ◽  
Branched Chain Amino Acid ◽  
Keto Acids ◽  
Perfused Rat Kidney ◽  
Branched Chain ◽  
Branched Chain Keto Acids ◽  
Isolated Rat

Isolated rat kidney perfused without substrate released serine, glycine, and taurine, and substantially smaller amounts of other amino acids. When branched-chain keto acids were added, the corresponding amino acids were released at rates amounting to 15-25% of keto acid disappearance. Perfusion with 2 mM alpha-keto-isovalerate or alpha-keto-beta-methylvalerate caused an increased glucose release amounting to 18-23% of keto acid disappearance. The activity of branched-chain amino acid transferase (BATase) was significantly stimulated by perfusion with the analogue of leucine, but not by perfusion with alpha-ketoglutarate, the analogues of valine or isoleucine, or with leucine itself. These findings document that the kidney converts branched-chain keto acids in part to the corresponding amino acids and suggest that the keto analogue of leucine may be involved in the control of renal BATase activity, thereby indirectly regulating the metabolism of branched-chain amino acids.

BLOOD BRANCHED-CHAIN AMINO AND α-KETO ACID CONCENTRATIONS AND NET EXCHANGE ACROSS THE PORTAL-DRAINED VISCERA AND HINDLIMB OF FED AND FASTED RUMINANTS

1987 ◽  
Vol 67 (4) ◽  
pp. 1011-1020 ◽  
Author(s):  
RICHARD J. EARLY ◽  
JAMES R. THOMPSON ◽  
ROBERT J. CHRISTOPHERSON ◽  
GARY W. SEDGWICK
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hind Limb ◽  
Venous Blood ◽  
Branched Chain Amino Acids ◽  
Keto Acid ◽  
Branched Chain Amino Acid ◽  
Keto Acids ◽  
Branched Chain ◽  
Cattle And Sheep

In the first of two experiments, whole blood branched-chain amino acid (BCAA) and plasma branched-chain α-keto acid (BCKA) concentrations in jugular venous blood were determined in cattle and sheep before and during a 6-d fast. In cattle, concentrations of valine, isoleucine, α-ketoisovalerate (KIV) and α-ketomethylvalerate (KMV) remained unchanged whereas leucine and α-ketoisocaproate (KTC) increased (P < 0.05) during fasting. In sheep, only KIV and KMV remained unchanged whereas BCAA and KIC increased (P < 0.05) during fasting. In a second experiment on cattle chronically catheterized to measure BCAA and BCKA exchange across the portal-drained viscera (PDV) and hindlimb (HL), the PDV added and the HL removed BCAA from the blood of fed cattle. The opposite exchange occurred after a 6-d fast. Releases of BCKA from the PDV and HL in both fed and fasted states were small compared to BCAA exchanges. The data suggest that blood BCAA but not BCKA concentrations may respond differently to starvation in sheep versus cattle and that in cattle the PDV and HL do not release appreciable amounts of BCKA relative to the net movements of the BCAA. Key words: Portal-drained viscera, hind limb, branched-chain amino acids, branched-chain α-keto acids, fasting, ruminants

Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phox knock-out mice

2017 ◽  
Vol 95 (4) ◽  
pp. 482-490 ◽  
Author(s):  
Zivar Yousefipour ◽  
Neha Chug ◽  
Katarzyna Marek ◽  
Alicia Nesbary ◽  
Joseph Mathew ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Mass ◽  
Total Antioxidant Status ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Knock Out ◽  
Total Antioxidant ◽  
In The Wild ◽  
Knock Out Mice

Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91phox knock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass)–1 by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass)–1·day–1, orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P < 0.05) in the wild type (WT) and KO mice. GW1929 reduced 8-isoprostane (by 32% and 40% in WT and KO mice, respectively) and increased PPARγ activity (by 81% and 92% in WT and KO, respectively). Chemokine activity was increased (by 63%) in acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P < 0.05), which was improved by GW1929 (by 75% and 74%). The levels of NF-κB were higher in acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.

scholarly journals The Intermediates in Branched-Chain Amino Acid Biosynthesis Are Indispensable for Conidial Germination of the Insect-Pathogenic Fungus Metarhizium robertsii

2020 ◽  
Vol 86 (20) ◽  
Author(s):  
Feifei Luo ◽  
Hongxia Zhou ◽  
Xue Zhou ◽  
Xiangyun Xie ◽  
You Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Pathogenic Fungus ◽  
Pathogenic Fungi ◽  
Conidial Germination ◽  
Keto Acid ◽  
Metarhizium Robertsii ◽  
Content Type ◽  
Branched Chain Amino Acid ◽  
Key Enzyme ◽  
Branched Chain

ABSTRACT Metarhizium spp. are well-known biocontrol agents used worldwide to control different insect pests. Keto-acid reductoisomerase (ILVC) is a key enzyme for branched-chain amino acid (BCAA) biosynthesis, and it regulates many physiological activities. However, its functions in insect-pathogenic fungi are poorly understood. In this work, we identified MrilvC in M. robertsii and dissected its roles in fungal growth, conidiation, germination, destruxin biosynthesis, environmental stress response, and insecticidal virulence. BCAA metabolism affects conidial yields and germination. However, BCAAs cannot recover the conidial germination of an MrilvC-deficient strain. Further feeding assays with intermediates showed that some conidia of the ΔMrilvC mutant start to germinate. Therefore, it is the germination defect that causes the complete failures of conidial penetration and pathogenicity in the ΔMrilvC mutant. In conclusion, we found intermediates in BCAA biosynthesis are indispensable for Metarhizium robertsii conidial germination. This study will advance our understanding of the fungal germination mechanism. IMPORTANCE Branched-chain amino acid (BCAA) metabolism plays a significant role in many biological activities beyond protein synthesis. Spore germination initiates the first stage of vegetative growth, which is critical for the virulence of pathogenic fungi. In this study, we demonstrated that the keto-acid reductoisomerase MrILVC, a key enzyme for BCAA biosynthesis, from the insect-pathogenic fungus Metarhizium robertsii is associated with conidial germination and fungal pathogenicity. Surprisingly, the germination of the ΔMrilvC mutant was restored when supplemented with the intermediates of BCAA metabolism rather than three BCAAs. The result was significantly different from that of plant-pathogenic fungi. Therefore, this report highlights that the intermediates in BCAA biosynthesis are indispensable for conidial germination of M. robertsii.

scholarly journals Adverse Adipose Phenotype and Hyperinsulinemia in Gravid Mice Deficient in Placental Growth Factor

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2176-2183 ◽  
Author(s):  
Bianca Hemmeryckx ◽  
Rita van Bree ◽  
Berthe Van Hoef ◽  
Lisbeth Vercruysse ◽  
H. Roger Lijnen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Adrenergic Receptors ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipocyte Hypertrophy ◽  
Endothelial Growth Factor

Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here we studied young-adult PlGF-deficient (PlGF−/−) and wild-type mice on a high-fat diet in the nongravid state and at embryonic day (E) 13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF−/− pregnancies. PlGF−/− mice showed altered intraadipose dynamics, with the following: 1) less blood vessels and fewer brown, uncoupling protein (UCP)-1-positive, adipocytes in white sc and perigonadal fat compartments and 2) white adipocyte hypertrophy. The mRNA expression of β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1 was decreased accordingly. Moreover, PlGF−/− mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF−/− and wild-type dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (vascular endothelial growth factor receptor-1, peroxisome proliferator-activated receptor-γ2) and thermogenesis (β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1) genes was down-regulated; circulating insulin levels gradually increased during pregnancy. In conclusion, reduced adipose vascularization in PlGF−/− mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia. Pregnancy adds to these changes by PlGF-independent mechanisms. Disturbed intraadipose dynamics is a novel mechanism to explain metabolic changes in late pregnancy in general and preeclamptic pregnancy in particular.

Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle.

1978 ◽  
Vol 234 (5) ◽  
pp. E494 ◽  
Author(s):  
H S Paul ◽  
S A Adibi
Keyword(s):  
Amino Acids ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Diabetic Rats ◽  
Acid Oxidation ◽  
Acyltransferase Activity ◽  
Remarkable Effect ◽  
Carnitine Acyltransferase ◽  
Branched Chain Amino Acid ◽  
Branched Chain

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.

scholarly journals Branched-Chain Fatty Acids as Mediators of the Activation of Hepatic Peroxisome Proliferator-Activated Receptor Alpha by a Fungal Lipid Extract

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1259 ◽  
Author(s):  
Garima Maheshwari ◽  
Robert Ringseis ◽  
Gaiping Wen ◽  
Denise K. Gessner ◽  
Johanna Rost ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Reporter Gene ◽  
Target Genes ◽  
Reporter Gene Assay ◽  
Lipid Extract ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Branched Chain Fatty Acids ◽  
Gene Assay ◽  
Branched Chain

The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated with the monomethyl BCFAs 12-methyltridecanoic acid (MTriA), 12-methyltetradecanoic acid (MTA), isopalmitic acid (IPA) and 14-methylhexadecanoic acid (MHD), and the direct activation of PPARalpha was evaluated by reporter gene assay using a PPARalpha responsive reporter gene. Furthermore, Fao cells were incubated with different concentrations of the CHLE and PPARalpha activation was also evaluated by using the reporter gene assay, and by determining the mRNA concentrations of selected PPARalpha target genes by real-time RT-PCR. The reporter gene assay revealed that IPA and the CHLE, but not MTriA, MHD and MTA, activate the PPARalpha responsive reporter gene. CHLE dose-dependently increased mRNA concentrations of the PPARalpha target genes acyl-CoA oxidase (ACOX1), cytochrome P450 4A1 (CYP4A1), carnitine palmitoyltransferase 1A (CPT1A) and solute carrier family 22 (organic cation/carnitine transporter), member 5 (SLC22A5). In conclusion, the monomethyl BCFA IPA is a potent PPARalpha activator. CHLE activates PPARalpha-dependent gene expression in Fao cells, an effect that is possibly mediated by IPA.

scholarly journals Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Fen Xu ◽  
David Burk ◽  
Zhanguo Gao ◽  
Jun Yin ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Nuclear Factor Κb ◽  
The Body ◽  
Sirtuin 1 ◽  
Vascular Density ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.

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