beta oxidation
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2022 ◽  
Author(s):  
Berra Erkosar ◽  
Cindy Dupuis ◽  
Fanny Cavigliasso ◽  
Loriane Savary ◽  
Hector Gallart-Ayala ◽  
...  

Juveniles are often first to suffer from nutrient shortage, and juvenile undernutrition is likely an important force of natural selection shaping animal physiology, with consequences potentially extending into adulthood. We combined RNAseq, targeted metabolomics and genomics to study the consequences of experimental evolution under juvenile undernutrition for metabolism of reproductively active adult females of Drosophila melanogaster. Compared to six Control populations maintained on standard diet, six Selected populations evolved for over 230 generations on a nutrient-poor larval diet showed major changes in adult gene expression and metabolite abundance. In particular, Selected flies were relatively deficient in essential amino acids and purine nucleotides, but showed overabundance of several non-essential amino-acids involved in purine synthesis and overexpression of multiple enzymes catalyzing this pathway. Selected flies also accumulated medium-chain acylcarnitines suggestive of congestion in beta-oxidation, possibly linked to deficiency of electron transporters. Some aspects of the metabolic profile of Selected flies resembled that of flies subject to starvation. Furthermore, differences between Selected and Control populations in adult gene expression were in general positively correlated with differences in larval expression, consistent with pleiotropy in gene regulation between the life stages. Finally, Selected flies were less fit in terms of fecundity than Controls even when both were raised under the conditions under which the Selected populations evolved. These results suggest that evolutionary adaptation to juvenile undernutrition has large pleiotropic consequences for adult metabolism, and that they are costly rather than adaptive for adult fitness.


2021 ◽  
Author(s):  
Daniel Antonelo ◽  
Mariane Beline ◽  
Saulo L. Silva ◽  
Juan F. M. Gómez ◽  
Christina Ferreira ◽  
...  

Muscle from cattle reared under different finishing regime (grain vs. forage) and growth rate may have divergent metabolic signatures that are reflective of their inherent differences in biochemical processes that may impact its subsequent transformation into high quality beef. Differences in muscle lipid profiles were characterized in Angus x Nellore crossbred steers, using multiple reaction monitoring (MRM)-profiling, to identify potential metabolic signatures correlated to beef color and tenderness in the longissimus thoracis muscle of cattle fed in either a feedlot- or pasture-based system programmed to achieve either a high or low growth rate. A total of 440 MRMs were significant, which were related mainly to triglycerides and phosphatidylcholine lipids. Distinct clusters between feeding strategies for the lipid dataset were revealed, which affected glycerolipid metabolism (P = 0.004), phospholipid metabolism (P = 0.009), sphingolipid metabolism (P = 0.050) and mitochondrial beta-oxidation of long chain saturated fatty acids (P = 0.073) pathways. Lipid content and profile differed to feeding strategies, which were related to L*, a*, and tenderness. These findings provide a comprehensive and in-depth understanding of lipidomic profiling of beef cattle finished under different feeding strategies and provides a basis for the relationship between lipid content and profiles and beef quality development.


2021 ◽  
Author(s):  
Yan Chen ◽  
Yang Liu ◽  
Yucen Bai ◽  
Shaogang Xu ◽  
Xiaofei Yang ◽  
...  

Abstract Changes in the metabolic profile within the intestine of lenok (Brachymystax lenok) when challenged to acute and lethal heat stress (HS) are studied using no-target HPLC-MS/MS metabonomic analysis. Of 51 differentially expressed metabolites identified in response to HS, 34 occurred in the positive ion mode and 17 in negative ion mode (VIP > 1, P < 0.05). Changes in metabolites (i.e. alpha-D-glucose, stachyose and L-lactate) related to carbohydrate and glycolysis are identified in HS-treated lenok. Fatty acid β-oxidation in HS-treated lenok was inhibited by accumulation of acetyl carnitine, palmitoylcarnitine, carnitine, and erucic acid. Many amino acids (L-tryptophan, D-proline, L-leucine, L-phenylalanine, L-aspartate, L-tyrosine, L-methionine, L-histidine and L-glutamine) decreased to support energy demands in HS-treated lenok. Oxidative damage in HS-treated lenok was indicated by decreased glycerophospholipid metabolites (i.e. glycerophosphocholine, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine, 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine, and 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine), and increased oxylipin production (12-HETE and 9R, 10S-EpOME). Oxidative stress increased formation of eicosanoids and dicarboxylic acids, overwhelming the mitochondrial β-oxidation pathway, while minor oxidative pathways (omega-oxidation and peroxisomal beta-oxidation) were likely to be activated in HS-treated lenok.


2021 ◽  
pp. 110-117
Author(s):  
M. E. Statsenko ◽  
S. V. Turkina ◽  
Yu. E. Lopushkova

The article reviews the efficacy of meldonium in patients with various diseases, which are based on secondary mitochondrial dysfunction. Mitochondria are complex cellular organelles that control many metabolic processes, including fatty acid oxidation, the Krebs cycle, oxidative phosphorylation in the electron transport chain, and many other processes. Many conditions can lead to secondary mitochondrial dysfunction and affect other diseases. Damage to mitochondria can promote the activation of free radical processes and the  initiation of  the  mechanisms of  programmed cell death, mitochondrial dysfunction decrease in the immune response, increase in the activity of the body’s inflammatory response in various infections. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. The article presents data on the effectiveness of using meldonium as a drug that helps to arrest pathological processes in mitochondria. The main mechanism of action of meldonium is based on a decrease in L-carnitine levels and increase of peroxisomes activity in the cytosol Meldonium was designed as a inhibitor of carnitine biosynthesis aimed to prevent accumulation of cytotoxic intermediate products of fatty acid beta- oxidation in ischemic tissues and to block this highly oxygen- consuming process. It is based on the correction of the energy metabolism of the cell. There was a positive trend in the use of meldonium in patients with diseases of the cardiovascular system (chronic ischemic diseases, chronic heart failure, arterial hypertension, etc.), neurological disorders (stroke, cerebrovascular insufficiency, etc.), respiratory diseases. The data on the beneficial effect of meldonium on the immune response in patients with coronavirus, bronchial asthma, chronic obstructive pulmonary disease, during vaccination with anti-influenza serum are presented. A decrease in asthenia was noted against the background of the use of meldonium in patients who had undergone coronavirus infection.


2021 ◽  
pp. 101298
Author(s):  
Sebastiaan van Liempd ◽  
Diana Cabrera ◽  
Carolin Pilzner ◽  
Heike Kollmus ◽  
Klaus Schughart ◽  
...  
Keyword(s):  

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Cristina M Arenaz ◽  
Gaurav Baranwal ◽  
Bethany L Goodlett ◽  
Joseph M Rutkowski ◽  
Robert C Alaniz ◽  
...  

Recent studies suggest that the microbiome plays a key role in hypertension and associated inflammation. Microbiota produce metabolites that may lead to activated pro-inflammatory immune cells and contribute to hypertension; however, the altered metabolites in multiple models of hypertension is currently unknown. We hypothesized that there are significant differences in metabolomic profiles between normotensive and hypertensive mice. We utilized two mouse models of hypertension: L-arginine methyl ester hydrochloride (L-NAME)/high salt diet induced hypertension (LSHTN) and angiotensin II induced hypertension (A2HTN). Serum and fecal samples were collected at the end of the treatment period. Ultra-high performance liquid chromatography and tandem mass spectrometry were performed to identify the biochemical composition of each sample. Random Forest Analysis was performed to classify each sample based on similarities and differences in metabolite composition. These procedures were performed by Metabolon, Inc. A total of 1,066 and 1,028 biochemicals were measured in serum and feces, respectively. There were 263 biochemicals in LSHTN serum and 122 biochemicals in A2HTN serum that were statistically different from controls (p≤0.05). There were 298 biochemicals in LSHTN feces and 64 biochemicals in A2HTN feces that were statistically different from controls (p≤0.05). Five biochemical metabolite groups were shown to have significant differences between hypertensive groups and controls: aromatic amino acids, bile acids and sterols, benzoates, fatty acids, and diacylglycerols. Tryptophan metabolites were significantly reduced in the serum of LSHTN mice but not in the serum of A2HTN mice. Serum tyrosine and benzoate metabolites showed varied differences between the two hypertensive groups. Serum fatty acid beta oxidation metabolites were significantly reduced in both hypertensive models but were significantly increased in the feces of mice with LSHTN. In conclusion, this study provided significant analysis of metabolite changes in two hypertension mouse models. Further investigation of the roles these metabolites play in hypertension may lead to targeted therapeutic interventions.


Pathology ◽  
2021 ◽  
Author(s):  
Yuji Sekine ◽  
Kouhei Yamamoto ◽  
Morito Kurata ◽  
Ayaka Honda ◽  
Iichiroh Onishi ◽  
...  

2021 ◽  
Author(s):  
Qiang Yan ◽  
William Cordell ◽  
Michael Jindra ◽  
Dylan Courtney ◽  
Madeline Kuckuk ◽  
...  

Abstract Microbial lipid metabolism is an attractive route for producing aliphatic chemicals, commonly referred to as oleochemicals. The predominant metabolic engineering strategy centers on heterologous thioesterases capable of producing fatty acids of desired size. To convert acids to desired oleochemicals (e.g. fatty alcohols, ketones), metabolic engineers modify cells to block beta-oxidation, reactivate fatty acids as coenzyme-A thioesters, and redirect flux towards termination enzymes with broad substrate utilization ability. These genetic modifications narrow the substrate pool available for the termination enzyme but cost one ATP per reactivation - an expense that could be saved if the acyl-chain was directly transferred from ACP- to CoA-thioester. In this work, we demonstrate an alternative acyl-transferase strategy for producing medium-chain oleochemicals. Through bioprospecting, mutagenesis, and metabolic engineering, we developed strains of Escherichia coli capable of producing over 1 g/L of medium-chain free fatty acids, fatty alcohols, and methyl ketones using the transacylase strategy.


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