scholarly journals A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism

2021 ◽  
Vol 4 (8) ◽  
pp. e202000863
Author(s):  
Angel Loza-Valdes ◽  
Alexander E Mayer ◽  
Toufic Kassouf ◽  
Jonathan Trujillo-Viera ◽  
Werner Schmitz ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Amino Acid Metabolism ◽  
Biochemical Analysis ◽  
Acid Metabolism ◽  
Phenylalanine Hydroxylase ◽  
Molecular Targets ◽  
Protein Kinase D ◽  
High Fat ◽  
Tyrosine Metabolism

Members of the protein kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver of animals fed a high-fat diet. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified more than 300 putative targets of PKD3. Furthermore, biochemical analysis revealed that PKD3 regulates cAMP-dependent PKA activity, a master regulator of the hepatic response to glucagon and fasting. PKA regulates glucose, lipid, and amino acid metabolism in the liver, by targeting key enzymes in the respective processes. Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. Consistently, we showed that PKD3 is activated by glucagon and promotes glucose and tyrosine levels in hepatocytes. Therefore, our data indicate that PKD3 might play a role in the hepatic response to glucagon.

scholarly journals A phosphoproteomic approach reveals that PKD3 controls phenylalanine and tyrosine metabolism

2020 ◽  
Author(s):  
Alexander E. Mayer ◽  
Angel Loza-Valdes ◽  
Werner Schmitz ◽  
Jonathan Trujillo Viera ◽  
Michael Leitges ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Phenylalanine Hydroxylase ◽  
Molecular Targets ◽  
Protein Kinase D ◽  
Primary Hepatocytes ◽  
Phenylalanine Concentration ◽  
Proteomic Approach ◽  
Tyrosine Metabolism ◽  
Phenylalanine Metabolism

SummaryMembers of the Protein Kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified over three-hundred putative targets of PKD3. Among them phenylalanine hydroxylase (PAH). PAH catalyses the conversion of phenylalanine to tyrosine and its activity is regulated by, phenylalanine concentration and glucagon-induced signaling. Consistently, we showed that PKD3 is activated by glucagon and promotes tyrosine levels in primary hepatocytes and liver of mice.Taken together, our comprehensive proteomic approach established that PKD3 determine the rate of phenylalanine to tyrosine conversion in the liver. Therefore, our data indicate that PKD3 might play a role in development of diseases related to the defective tyrosine and phenylalanine metabolism.

scholarly journals Metabolomic Analysis of Biochemical Changes in the Plasma of High-Fat Diet and Streptozotocin-Induced Diabetic Rats after Treatment with Isoflavones Extract of Radix Puerariae

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Zhang ◽  
Ping Wang ◽  
Youdong Xu ◽  
Xianli Meng ◽  
Yi Zhang
Keyword(s):  
Liquid Chromatography ◽  
Amino Acid ◽  
Discriminant Analysis ◽  
Least Squares ◽  
High Fat Diet ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Diabetic Rats ◽  
High Fat ◽  
Radix Puerariae

The main purpose of this study was to investigate the protective effects of total isoflavones from Radix Puerariae (PTIF) in diabetic rats. Diabetes was induced by a high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ; 40 mg/kg). At 26 weeks onwards, PTIF 421 mg/kg was administrated to the rats once daily consecutively for 10 weeks. Metabolic profiling changes were analyzed by Ultraperformance Liquid Chromatography-Quadrupole-Exactive Orbitrap-Mass Spectrometry (UPLC-Q-Exactive Orbitrap-MS). The principal component discriminant analysis (PCA-DA), partial least-squares discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used for multivariate analysis. Moreover, free amino acids in serum were determined by high-performance liquid chromatography with fluorescence detector (HPLC-FLD). Additionally, oxidative stress and inflammatory cytokines were evaluated. Eleven potential metabolite biomarkers, which are mainly related to the coagulation, lipid metabolism, and amino acid metabolism, have been identified. PCA-DA scores plots indicated that biochemical changes in diabetic rats were gradually restored to normal after administration of PTIF. Furthermore, the levels of BCAAs, glutamate, arginine, and tyrosine were significantly increased in diabetic rats. Treatment with PTIF could regulate the disturbed amino acid metabolism. Consequently, PTIF has great therapeutic potential in the treatment of DM by improving metabolism disorders and inhibiting oxidative damage.

scholarly journals Sex-specific Metabolic Characterization of Serum and Liver of Mice with High-fat Diet

2020 ◽  
Author(s):  
Yi Zhou ◽  
Chen Li ◽  
Xinyi Wang ◽  
Qinbo Chen ◽  
Pengxi Deng ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Male Mice ◽  
High Fat ◽  
Metabolic Pattern ◽  
Male And Female ◽  
Female Mice

Abstract Background: Obesity exhibit sex differences is well established, but its metabolic mechanism remains unclear. Thus, investigation of metabolic pattern of male and female mice with high-fat diet (HFD) is of substantial importance for explore the potential mechanism linking gender differences in obesity.Methods: In the present study, we analyzed the metabolic changes in serum and liver of male and female mice with high-fat diet using nuclear magnetic resonance-based metabolomic approach.Results: Principle component analysis show that the metabolic pattern of serum and liver of male mice with HFD was significantly distinguished from the other groups. Furthermore, the accumulation of low-density lipoprotein/very low-density lipoprotein was found in the serum of male mice with HFD. Moreover, metabolomic results of liver reveal that tricarboxylic acid cycle and amino acid metabolism are increased in female mice with HFD.Conclusion: In conclusion, our results suggest that the differences in energy and amino acid metabolism of males and females were most likely influence the predisposition to obesity.

scholarly journals Ginsenoside Rb1 ameliorates Glycemic Disorder in Mice With High Fat Diet-Induced Obesity via Regulating Gut Microbiota and Amino Acid Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueyuan Yang ◽  
Bangjian Dong ◽  
Lijun An ◽  
Qi Zhang ◽  
Yao Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sequencing Analysis ◽  
Ginsenoside Rb1 ◽  
High Fat ◽  
The Impact

Accumulating evidences suggested an association between gut microbiome dysbiosis and impaired glycemic control. Ginsenoside Rb1 (Rb1) is a biologically active substance of ginseng, which serves anti-diabetic effects. However, its working mechanism especially interaction with gut microbes remains elusive in detail. In this study, we investigated the impact of Rb1 oral supplementation on high fat diet (HFD) induced obesity mice, and explored its mechanism in regulating blood glucose. The results showed that higher liver weight and lower cecum weight were observed in HFD fed mice, which was maintained by Rb1 administration. In addition, Rb1 ameliorated HFD induced blood lipid abnormality and improved insulin sensitivity. Several mRNA expressions in the liver were measured by quantitative real-time PCR, of which UCP2, Nr1H4, and Fiaf were reversed by Rb1 treatment. 16S rRNA sequencing analysis indicated that Rb1 significantly altered gut microbiota composition and increased the abundance of mucin-degrading bacterium Akkermansia spp. compared to HFD mice. As suggested via functional prediction, amino acid metabolism was modulated by Rb1 supplementation. Subsequent serum amino acids investigation indicated that several diabetes associated amino acids, like branched-chain amino acids, tryptophan and alanine, were altered in company with Rb1 supplementation. Moreover, correlation analysis firstly implied that the circulation level of alanine was related to Akkermansia spp.. In summary, Rb1 supplementation improved HFD induced insulin resistance in mice, and was associated with profound changes in microbial composition and amino acid metabolism.

Plasma homocysteine level and hepatic sulfur amino acid metabolism in mice fed a high-fat diet

2012 ◽  
Vol 52 (1) ◽  
pp. 127-134 ◽  
Author(s):  
Kang Uk Yun ◽  
Chang Seon Ryu ◽  
Jung Min Oh ◽  
Chung Hyun Kim ◽  
Kye Sook Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Fat Diet ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Homocysteine Level ◽  
Plasma Homocysteine ◽  
Sulfur Amino Acid ◽  
High Fat ◽  
Plasma Homocysteine Level

scholarly journals Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5390
Author(s):  
Qianhui Zeng ◽  
Nannan Wang ◽  
Yaru Zhang ◽  
Yuxuan Yang ◽  
Shuangshuang Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Glycolipid Metabolism ◽  
Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

scholarly journals Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet (Running Title: Sdc4 Deficiency Affects Metabolic Phenotypes)

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2810 ◽  
Author(s):  
Maria De Luca ◽  
Denise Vecchie’ ◽  
Baskaran Athmanathan ◽  
Sreejit Gopalkrishna ◽  
Jennifer A. Valcin ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Serum Triglyceride ◽  
Independent Study ◽  
Whole Body ◽  
Elderly Subjects ◽  
Sensitivity Index ◽  
High Fat ◽  
Metabolic Phenotypes

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

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