<i>ALAS1</i> gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice

Oliveri, Leda; Davio, Carlos; Batlle, Alcira; Gerez, Esther Noemí

doi:10.1042/bj20111005

Cited by 26 publications

(21 citation statements)

References 53 publications

(62 reference statements)

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“…Furthermore, losing weight can be very difficult for these patients due to the risk of attacks induced by fasting. 28 In the present study, the results for BIA were higher in the porphyric patients than in the control.…”

Section: Discussioncontrasting

confidence: 44%

“…Acute porphyrias attacks can be triggered by fasting or carbohydrate restriction and are usually treated by the administration of glucose. 2 , 28 The therapeutic intake of carbohydrates leads patients with AIP gaining weight. Furthermore, losing weight can be very difficult for these patients due to the risk of attacks induced by fasting.…”

Section: Discussionmentioning

confidence: 99%

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Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria Patients

et al. 2015

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The porphyrias are a group of rare metabolic disorders. The incidence and prevalence are low because the acute intermittent porphyria (AIP) is rare. Our aim was to assess the use of anthropometric and quality-of-life parameters in porphyric patients in order to identify predictor factors that might help in characterizing AIP patients.Sixteen AIP patients from Murcia (Spain) were recruited from local health centers in 2008 and 2009. A control group of 16 healthy people was established. Body composition was assessed by bioelectrical impedance analysis (BIA) and anthropometric measurements: body weight; height; knee-heel height; waist, hip, upper arm and calf circumferences (CCs); biacromion and biiliac diameters; bicondylar and biepicondylar width; and triceps, subscapular, supraspinale, and calf skinfold thickness. Anthropometric indicators were obtained from anthropometric measurements. A quality-of-life evaluation was carried out using the EuroQol-5D (EQ-5D) questionnaire and Barthel and Katz indexes. Significant differences in means were tested by unpaired Student t test. Group differences in anthropometric measurements were tested with a 2-way analysis of variance (group × condition: age group, overweight, and adiposity degree). Relative frequencies were obtained for noncontinuous variables. Significant differences in prevalence were calculated by means of χ2.AIP patients showed statistically significant differences in terms of knee-heel height, biiliac diameter, CC, triceps skinfold thickness, BIA, ponderal index, endomorphy, and ectomorphy. Only 1 quality-of-life indicator, visual analog scale, in the EQ-5D questionnaire showed significant differences between porphyric and control groups.Some anthropometric parameters and the EQ-5D questionnaire could be used to appreciate the presence or follow the evolution of the disease in AIP patients.

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Section: Discussioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria Patients

et al. 2015

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“…Furthermore, the following genes are involved in diabetes and insulin signaling: MDH2 [ 57 ], PPP1CA [ 58 ] and HRAS [ 59 ]. Also, within the 10 genes which expression significantly correlated with BMI fold change during the weight maintenance phase ( Table 3 ), GNG2 [ 60 ] is involved in diabetes pathways, while ALAS1 has been shown to be induced in diabetes in mice [ 30 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

Network Analysis of Metabolite GWAS Hits: Implication of CPS1 and the Urea Cycle in Weight Maintenance

Matone¹,

Scott-Boyer²,

Carayol³

et al. 2016

PLoS ONE

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Background and ScopeWeight loss success is dependent on the ability to refrain from regaining the lost weight in time. This feature was shown to be largely variable among individuals, and these differences, with their underlying molecular processes, are diverse and not completely elucidated. Altered plasma metabolites concentration could partly explain weight loss maintenance mechanisms. In the present work, a systems biology approach has been applied to investigate the potential mechanisms involved in weight loss maintenance within the Diogenes weight-loss intervention study.Methods and ResultsA genome wide association study identified SNPs associated with plasma glycine levels within the CPS1 (Carbamoyl-Phosphate Synthase 1) gene (rs10206976, p-value = 4.709e-11 and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tissue showed that CPS1 expression levels were associated with successful weight maintenance and with several SNPs within CPS1 (cis-eQTL). In order to contextualize these results, a gene-metabolite interaction network of CPS1 and glycine has been built and analyzed, showing functional enrichment in genes involved in lipid metabolism and one carbon pool by folate pathways.ConclusionsCPS1 is the rate-limiting enzyme for the urea cycle, catalyzing carbamoyl phosphate from ammonia and bicarbonate in the mitochondria. Glycine and CPS1 are connected through the one-carbon pool by the folate pathway and the urea cycle. Furthermore, glycine could be linked to metabolic health and insulin sensitivity through the betaine osmolyte. These considerations, and the results from the present study, highlight a possible role of CPS1 and related pathways in weight loss maintenance, suggesting that it might be partly genetically determined in humans.

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“…It is important to point out that the activity and cellular distribution of FoxO1 is regulated by Akt [39]. FoxO1 is a transcriptional factor that controls the expression of ALAS1 [33], [40]. ALAS1 controls the rate-limiting step in heme biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Uridine Affects Liver Protein Glycosylation, Insulin Signaling, and Heme Biosynthesis

Urasaki

Pizzorno

2014

PLoS ONE

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Purines and pyrimidines are complementary bases of the genetic code. The roles of purines and their derivatives in cellular signal transduction and energy metabolism are well-known. In contrast, the roles of pyrimidines and their derivatives in cellular function remain poorly understood. In this study, the roles of uridine, a pyrimidine nucleoside, in liver metabolism are examined in mice. We report that short-term uridine administration in C57BL/6J mice increases liver protein glycosylation profiles, reduces phosphorylation level of insulin signaling proteins, and activates the HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. Short-term uridine administration is also associated with reduced liver hemin level and reduced ability for insulin-stimulated blood glucose removal during an insulin tolerance test. Some of the short-term effects of exogenous uridine in C57BL/6J mice are conserved in transgenic UPase1 −/− mice with long-term elevation of endogenous uridine level. UPase1 −/− mice exhibit activation of the liver HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. UPase1 −/− mice also exhibit impaired ability for insulin-stimulated blood glucose removal. However, other short-term effects of exogenous uridine in C57BL/6J mice are not conserved in UPase1 −/− mice. UPase1 −/− mice exhibit normal phosphorylation level of liver insulin signaling proteins and increased liver hemin concentration compared to untreated control C57BL/6J mice. Contrasting short-term and long-term consequences of uridine on liver metabolism suggest that uridine exerts transient effects and elicits adaptive responses. Taken together, our data support potential roles of pyrimidines and their derivatives in the regulation of liver metabolism.

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ALAS1 gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice

Cited by 26 publications

References 53 publications

Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria Patients

Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria Patients

Network Analysis of Metabolite GWAS Hits: Implication of CPS1 and the Urea Cycle in Weight Maintenance

Uridine Affects Liver Protein Glycosylation, Insulin Signaling, and Heme Biosynthesis

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