scholarly journals Metabolomics of human fasting: new insights about old questions

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200176 ◽  
Author(s):  
Hiroshi Kondoh ◽  
Takayuki Teruya ◽  
Mitsuhiro Yanagida
Keyword(s):  
Pentose Phosphate Pathway ◽  
Weight Reduction ◽  
Glycogen Storage ◽  
Pentose Phosphate ◽  
Prolonged Fasting ◽  
Obese People ◽  
Transcriptional Modulators ◽  
Obese Subjects ◽  
Antioxidative Metabolites ◽  
Metabolomic Approach

Since ancient days, human fasting has been performed for religious or political reasons. More recently, fasting has been employed as an effective therapy for weight reduction by obese people, and numerous studies have investigated the physiology of fasting by obese subjects. Well-established fasting markers (butyrates, BCAAs and carnitines) were considered essential energy substitutes after glycogen storage depletion. However, a recently developed metabolomic approach has unravelled previously unappreciated aspects of fasting. Surprisingly, one-third (44) of 120 metabolites investigated increase during 58 h of fasting, including antioxidative metabolites (carnosine, ophthalmic acid, ergothioneine and urates) and metabolites of entire pathways, such as the pentose phosphate pathway. Signalling metabolites (3-hydroxybutyrate and 2-oxoglutarate) and purines/pyrimidines may also serve as transcriptional modulators. Thus, prolonged fasting activates both global catabolism and anabolism, reprogramming metabolic homeostasis.

Weight Change and Development of Subclinical Carotid Atherosclerosis Among Metabolically Healthy Adults: A Cohort Study

2019 ◽  
Vol 105 (3) ◽  
pp. e410-e416
Author(s):  
Dong Hyun Sinn ◽  
Danbee Kang ◽  
Soo Jin Cho ◽  
Yoosoo Chang ◽  
Seungho Ryu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Weight Change ◽  
Weight Reduction ◽  
Carotid Atherosclerosis ◽  
No Reduction ◽  
Cvd Risk ◽  
Obese People ◽  
Obese Subjects ◽  
Metabolically Healthy

Abstract Background The benefit of weight loss for reducing cardiovascular disease (CVD) risk in metabolically healthy obese people is unknown. Objectives We evaluated the association between weight change and incident subclinical carotid atherosclerosis (SCA) in metabolically healthy but overweight or obese subjects. Methods Cohort study of 3117 metabolically healthy overweight or obese adults who did not have any metabolic syndrome components or insulin resistance at baseline. SCA was assessed using carotid artery ultrasonography. The study outcome was the development of incident SCA among participants free of the disease at baseline. Results During 12 248 person-years of follow-up (median 3.42 years), 747 participants developed SCA. The proportions of participants with no reduction or increased weight, reduction in weight from 0.1% to 4.9%, and reduction in weight ≥ 5% during follow-up were 47.0%, 44.4%, and 8.6%, respectively. The fully-adjusted hazard ratios (HRs) for incident SCA in participants with a reduction in weight of 0.1% to 4.9% and ≥ 5% compared with those with no reduction or increased weight were 0.84 (95% CI, 0.72–0.98) and 0.66 (95% CI, 0.50–0.87), respectively. Conclusions In a large cohort study of metabolically healthy but overweight or obese adult men and women, weight reduction was associated with a lower incidence of SCA. Our findings suggest that metabolically healthy overweight or obese subjects may benefit from weight reduction in terms of CVD risk.

scholarly journals Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway

Cell Reports ◽  
2020 ◽  
Vol 30 (5) ◽  
pp. 1417-1433.e7 ◽  
Author(s):  
Michael M. Dubreuil ◽  
David W. Morgens ◽  
Kanji Okumoto ◽  
Masanori Honsho ◽  
Kévin Contrepois ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Systematic Identification

scholarly journals Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kazuya Matsuo ◽  
Kohkichi Hosoda ◽  
Jun Tanaka ◽  
Yusuke Yamamoto ◽  
Taichiro Imahori ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Pentose Phosphate Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pentose Phosphate ◽  
Cerebral Ischemia Reperfusion ◽  
Hsp27 Phosphorylation ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Preliminary Study

Abstract Background We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia–reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia–reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. Methods In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography–mass spectrometry to identify ischemia–reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia–reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. Results Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia–reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia–reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia–reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). Conclusions As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia–reperfusion injury.

scholarly journals Pentose Phosphate Pathway Reactions in Photosynthesizing Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1547
Author(s):  
Thomas D. Sharkey
Keyword(s):  
Pentose Phosphate Pathway ◽  
Strong Association ◽  
Pentose Phosphate ◽  
Critical Component ◽  
Reaction Sequence ◽  
Response To Stress ◽  
Labeling Pattern

The pentose phosphate pathway (PPP) is divided into an oxidative branch that makes pentose phosphates and a non-oxidative branch that consumes pentose phosphates, though the non-oxidative branch is considered reversible. A modified version of the non-oxidative branch is a critical component of the Calvin–Benson cycle that converts CO2 into sugar. The reaction sequence in the Calvin–Benson cycle is from triose phosphates to pentose phosphates, the opposite of the typical direction of the non-oxidative PPP. The photosynthetic direction is favored by replacing the transaldolase step of the normal non-oxidative PPP with a second aldolase reaction plus sedoheptulose-1,7-bisphosphatase. This can be considered an anabolic version of the non-oxidative PPP and is found in a few situations other than photosynthesis. In addition to the strong association of the non-oxidative PPP with photosynthesis metabolism, there is recent evidence that the oxidative PPP reactions are also important in photosynthesizing cells. These reactions can form a shunt around the non-oxidative PPP section of the Calvin–Benson cycle, consuming three ATP per glucose 6-phosphate consumed. A constitutive operation of this shunt occurs in the cytosol and gives rise to an unusual labeling pattern of photosynthetic metabolites while an inducible shunt in the stroma may occur in response to stress.

scholarly journals Fine tuning the glycolytic flux ratio of EP-bifido pathway for mevalonate production by enhancing glucose-6-phosphate dehydrogenase (Zwf) and CRISPRi suppressing 6-phosphofructose kinase (PfkA) in Escherichia coli

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying Li ◽  
He Xian ◽  
Ya Xu ◽  
Yuan Zhu ◽  
Zhijie Sun ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Conversion Rate ◽  
Metabolic Flux ◽  
Flux Ratio ◽  
Reducing Power ◽  
Pentose Phosphate ◽  
Fine Tuning ◽  
High Yield ◽  
Glycolytic Flux ◽  
Acetyl Coa

Abstract Background Natural glycolysis encounters the decarboxylation of glucose partial oxidation product pyruvate into acetyl-CoA, where one-third of the carbon is lost at CO2. We previously constructed a carbon saving pathway, EP-bifido pathway by combining Embden-Meyerhof-Parnas Pathway, Pentose Phosphate Pathway and “bifid shunt”, to generate high yield acetyl-CoA from glucose. However, the carbon conversion rate and reducing power of this pathway was not optimal, the flux ratio of EMP pathway and pentose phosphate pathway (PPP) needs to be precisely and dynamically adjusted to improve the production of mevalonate (MVA). Result Here, we finely tuned the glycolytic flux ratio in two ways. First, we enhanced PPP flux for NADPH supply by replacing the promoter of zwf on the genome with a set of different strength promoters. Compared with the previous EP-bifido strains, the zwf-modified strains showed obvious differences in NADPH, NADH, and ATP synthesis levels. Among them, strain BP10BF accumulated 11.2 g/L of MVA after 72 h of fermentation and the molar conversion rate from glucose reached 62.2%. Second, pfkA was finely down-regulated by the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system. The MVA yield of the regulated strain BiB1F was 8.53 g/L, and the conversion rate from glucose reached 68.7%. Conclusion This is the highest MVA conversion rate reported in shaken flask fermentation. The CRISPRi and promoter fine-tuning provided an effective strategy for metabolic flux redistribution in many metabolic pathways and promotes the chemicals production.

scholarly journals The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Guotai Sheng ◽  
Nan Peng ◽  
Chong Hu ◽  
Ling Zhong ◽  
Mingchun Zhong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Fatty Liver Disease ◽  
Chinese Population ◽  
Independent Predictor ◽  
Multiple Regression Model ◽  
Obese People ◽  
Alcoholic Fatty Liver ◽  
Obese Subjects ◽  
Alcoholic Fatty Liver Disease

Abstract Background The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. Methods The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. Results The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. Conclusions This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

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