2-oxoglutarate Research Articles

Castration alters the cecal microbiota and inhibits growth in Holstein cattle.

To determine the effects of castration on growth performance, serum hormone levels, cecal microbiota composition, and metabolites in cattle. A total of 18 Holstein bulls and steers were divided into bull and steer groups and randomly assigned to 3 pens (3 cattle per pen, and each cattle were separated by a fence) to determine the average daily gain (ADG), daily dry matter intake (DMI), and feed efficiency (G/F). After the finishing trial, six cattle per group were randomly slaughtered. Serum was collected to measure the hormone concentration, and the cecal content was collected to measure the pH, short-chain fatty acids, and digestive enzyme activities. Metagenome sequencing and untargeted metabolomics were used to investigate the microbiota composition, functional profiles, and differential metabolites of the cecal contents. We found that castration significantly decreased ADG, DMI, and G/F in cattle (P < 0.05). The serum testosterone, thyroxine, growth hormone (P < 0.05), and triiodothyronine (P < 0.01) concentrations significantly decreased in the steer group when compared to those of the bull group. The activities of cellulase, xylanase, pectinase, and β-glucosidase (P < 0.05) significantly decreased in the steer group, whereas the activities of lipase and α-amylase significantly increased. Moreover, castration significantly decreased the relative abundance of Ruminococcaceae_bacterium, Treponema_porcinum, Oscillibacter_sp. (P < 0.05), and Alistipes_senegalensis (P < 0.01), whereas the relative abundance of Phocaeicola_plebeius (P < 0.05) was significantly increased. Also, the relative abundance of Phocaeicola_plebeius was negatively correlated with testosterone levels, and the function of the cecal microbiota was enriched in the GH29 and GH97 families in the steer group. Metabolomic analysis indicated that castration increased the levels of L-valine, L-phenylalanine, L-aspartic acid, L-isoleucine, L-lysine, methionine, L-glutamic acid, and L-leucine, while decreasing the levels of α-ketoglutaric acid through the 2-oxocarboxylic acid metabolism pathway. In addition, α-ketoglutaric acid was negatively correlated with Oscillibacter_sp. (P < 0.01). Overall, castration can inhibit cattle growth by altering the composition of the cecal microbiota. Therefore, this study provides a theoretical and practical basis for improving the growth performance of steers.

L-lactic and 2-ketoglutaric Acids, Odors from Human Skin, Govern Attraction and Landing in Host-Seeking Female Aedes aegypti Mosquitoes

Aedes aegypti, presented with a source of L-lactic and 2-ketoglutaric acid in a wind-tunnel bioassay, takeoff, fly upwind, and land on the odorant substrate at rates comparable to those exhibited by mosquitoes presented with a skin-odor stimulus. Addition of carbon dioxide decreased takeoff latency but was not required to elicit upwind flight nor landings. Ketoglutaric acid, a recently identified component of human skin odor, combined with lactic acid elicits the full repertoire of mosquito host-seeking behaviors.

LBODP019 Vitamin D Levels In A Population With Type 2 Diabetes

Abstract Background Little is known about the impact of over-the-counter ketone supplementation, used by patients to promote weight loss, on ketosis and serum ketone values. Recent literature suggests that acute ingestion of exogenous ketones leads to increased blood beta-hydroxybutyrate and decreased blood glucose1. Clinical Case A 61-year-old man with a history of type 2 diabetes mellitus, atrial fibrillation, hypertension, and hyperlipidemia presented as a transfer to the neurocritical care ICU from an outside hospital for subarachnoid hemorrhage secondary to intracranial saccular aneurysm. His admission hemoglobin A1c was 9.9% (ref 4.4-5.6), blood glucose was 205 mg/dL (ref 70-99), beta-hydroxybutyrate was markedly elevated at 26.2 mg/dL (ref 0-3), and urinalysis showed 80mg/dL ketones (ref 0). Serum toxicology screen was notable for detectable acetone 8mg/dL (ref: none detected). His lactate was 2 mmol/L (ref 0.5-1.9), Cr 0.99mg/dL (0.67-1.17), and HCO3 22 mmol/L (ref 22-27). Arterial blood gas showed pH of 7.37 (ref 7.38-7.47), and an anion gap metabolic acidosis (AGMA) of 15 mmol/L (ref &amp;lt;12). Given the patient's profound ketosis, hyperglycemia, and mild AGMA, the patient was started on an insulin drip for presumed diabetic ketoacidosis (DKA). After 4 hours, the patient's anion gap had decreased to 12mmcol/L. The following day, he was transitioned to basal/bolus insulin, and underwent embolization of his cerebral aneurysm. After further recovery, Endocrinology was consulted for insulin recommendations. The patient denied any prior history of DKA or use of any SGLT2-inhibitors, and denied decreased oral intake or vomiting prior to admission. He did report taking ketone supplements, "Keto Strong: Ketogenic Weight Management – Advanced Formulation," two tabs (700mg "proprietary keto blend") BID for 2-3 years with ingredients listed as: sodium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, medium chain triglyceride oil, L-arginine, alpha-ketoglutaric acid, and 7-keto-dehydroepiandrosterone. Given a lack of acidosis, mild hyperglycemia, and mild lactic acidosis without risk factors for euglycemic DKA, it was suspected his profound ketosis out of proportion to clinical picture was secondary to ketone supplementation with a misdiagnosis of DKA. Conclusion This is one of the first cases to report profound ketosis in a hospitalized patient likely secondary to exogenous ketone supplementation. Ketosis secondary to nutritional supplementation should be considered once more common etiologies are ruled out. Additional research is needed to determine the role of exogenous ketone use on metabolism and glycemic control.

LBODP035 When Is Ketosis Just Ketosis?

Abstract Background Little is known about the impact of over-the-counter ketone supplementation, used by patients to promote weight loss, on ketosis and serum ketone values. Recent literature suggests that acute ingestion of exogenous ketones leads to increased blood beta-hydroxybutyrate and decreased blood glucose1. Clinical Case A 61-year-old man with a history of type 2 diabetes mellitus, atrial fibrillation, hypertension, and hyperlipidemia presented as a transfer to the neurocritical care ICU from an outside hospital for subarachnoid hemorrhage secondary to intracranial saccular aneurysm. His admission hemoglobin A1c was 9.9% (ref 4.4-5.6), blood glucose was 205 mg/dL (ref 70-99), beta-hydroxybutyrate was markedly elevated at 26.2 mg/dL (ref 0-3), and urinalysis showed 80mg/dL ketones (ref 0). Serum toxicology screen was notable for detectable acetone 8mg/dL (ref: none detected). His lactate was 2 mmol/L (ref 0.5-1.9), Cr 0.99mg/dL (0.67-1.17), and HCO3 22 mmol/L (ref 22-27). Arterial blood gas showed pH of 7.37 (ref 7.38-7.47), and an anion gap metabolic acidosis (AGMA) of 15 mmol/L (ref &amp;lt;12). Given the patient's profound ketosis, hyperglycemia, and mild AGMA, the patient was started on an insulin drip for presumed diabetic ketoacidosis (DKA). After 4 hours, the patient's anion gap had decreased to 12mmcol/L. The following day, he was transitioned to basal/bolus insulin, and underwent embolization of his cerebral aneurysm. After further recovery, Endocrinology was consulted for insulin recommendations. The patient denied any prior history of DKA or use of any SGLT2-inhibitors, and denied decreased oral intake or vomiting prior to admission. He did report taking ketone supplements, "Keto Strong: Ketogenic Weight Management – Advanced Formulation," two tabs (700mg "proprietary keto blend") BID for 2-3 years with ingredients listed as: sodium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, medium chain triglyceride oil, L-arginine, alpha-ketoglutaric acid, and 7-keto-dehydroepiandrosterone. Given a lack of acidosis, mild hyperglycemia, and mild lactic acidosis without risk factors for euglycemic DKA, it was suspected his profound ketosis out of proportion to clinical picture was secondary to ketone supplementation with a misdiagnosis of DKA. Conclusion This is one of the first cases to report profound ketosis in a hospitalized patient likely secondary to exogenous ketone supplementation. Ketosis secondary to nutritional supplementation should be considered once more common etiologies are ruled out. Additional research is needed to determine the role of exogenous ketone use on metabolism and glycemic control.

Inheritance of Fruit Weight, Size and Organic Acid Content in a Distant Hybrid Population of Longan ‘Huanongzao’ and Lychee ‘Ziniangxi’

The type and content of organic acids in fruits are important factors that determine the traits, such as the nutrition and flavor of fruits. Fruit weight and size are also very important economic characters in fruit breeding research. To investigate the inheritance patterns in longan, fruit organic acid contents, weight, and size were measured in the distant hybridization progenies of longan ‘Huanongzao’ and lychee ‘Ziniangxi’. The results revealed that the malic acid accumulation exhibited mid-parent heterosis, citric acid content showed a tendency towards depression, and oxalic acid, ketoglutaric acid, fumaric acid, gallic acid, and total acid contents exhibited transgressive inheritance. The inheritance patterns in fruit weight, length and diameter tended towards smaller and degraded. The coefficient of variation (CV) for the organic acids ranged from 35.77–90.20%, and the heritability (H2) was 72.35–97.44%. High CV (55.44%) coupled with medium H2 (28.72%) were observed in fruit weight, however, low CV (12.29% and 12.50%) coupled with high H2 (68.95% and 69.25%) were shown in fruit length and diameter. In this study, the genetic variation of acid contents, fruit weight and size in the F1 population of longan and lychee were analyzed for the first time, providing an informative and theoretical basis for the selection and breeding of longan cultivars.

Effects of In Ovo Injection of α-Ketoglutaric Acid on Hatchability, Growth, Plasma Metabolites, and Antioxidant Status of Broilers.

Recently, α-ketoglutaric acid (AKG) has gained importance as an antioxidant. Its dietary supplementation in animals and humans has proved beneficial. Moreover, an extensive group of studies on in ovo feeding has proved that it produces better day-old chicks and overall performance. Combining the two, we hypothesized that in ovo feeding of AKG could improve the antioxidant status in addition to chick quality and broiler performance. At 17.5 days of incubation, eggs were divided into one of five groups: eggs that received (i) no injection (U-CON), (ii) distilled water (DDW) only (0 AKG), (iii) 0.5% AKG dissolved in DDW (0.5 AKG), (iv) 1.0% AKG dissolved in DDW (1.0 AKG), or (v) 1.5% AKG dissolved in DDW (1.5 AKG). Chicks were raised until 21 days of age. Biological samples were collected on day 0 and day 21. Body weight (p = 0.020), average daily gain (p = 0.025), and average daily feed intake (p = 0.036) were found to quadratically increase with the amount of AKG during the grower phase. At day 0, the absolute (p = 0.040) and relative weight (p = 0.035) of the liver increased linearly with an increasing amount of AKG. The 0.5 AKG group had significantly higher plasma protein (p = 0.025), absolute and relative heart indices at day 0 (p = 0.006). An in ovo feeding of AKG improved the plasma antioxidant capacity of chicks at day 0 as compared to 0 AKG. AKG effect was seen on the plasma antioxidant balance, which increased linearly with the increasing dose of in ovo AKG. Furthermore, 1.0 AKG and 1.5 AKG showed a significant (p = 0.002) upregulation of the hepatic mRNA expression of nuclear factor erythroid 2-related factor (NRF2) in comparison to 0 AKG. The results imply that without negatively affecting hatchability performance, in ovo feeding of AKG has beneficial effects on the antioxidant status of broilers.

Metabolomics and lipidomics profiles related to intramuscular fat content and flavor precursors between Laiwu and Yorkshire pigs

Chinese indigenous pig breeds have higher intramuscular fat content (IMF) and better meat quality than Western commercial pigs. The differential metabolites and lipids in the skeletal muscle associated with IMF contents and meat flavor in Laiwu and Yorkshire pigs were investigated in this study. As a result, 113 differential metabolites and 54 differential lipids were discovered. Lipidomics revealed that the Laiwu pig had a fast lipid droplet formation and contained more triglyceride than the Yorkshire pig, which was corresponded to its high IMF contents. Both the lipidomics and metabolomics results indicated that the Laiwu pig had a higher mitochondrial content and aerobic respiration, due to its larger percentage of oxidative fibers. In addition, differential metabolites, such as oxoglutaric acid, fumarate, and l-aspartate, were thought to be important flavor precursors contributing to the Laiwu pig’s improved pork taste.

The α-Ketoglutarate Dehydrogenase Complex as a Hub of Plasticity in Neurodegeneration and Regeneration.

Abnormal glucose metabolism is central to neurodegeneration, and considerable evidence suggests that abnormalities in key enzymes of the tricarboxylic acid (TCA) cycle underlie the metabolic deficits. Significant recent advances in the role of metabolism in cancer provide new insight that facilitates our understanding of the role of metabolism in neurodegeneration. Research indicates that the rate-limiting step of the TCA cycle, the α-ketoglutarate dehydrogenase complex (KGDHC) and its substrate alpha ketoglutarate (KG), serve as a signaling hub that regulates multiple cellular processes: (1) is the rate-limiting step of the TCA cycle, (2) is sensitive to reactive oxygen species (ROS) and produces ROS, (3) determines whether KG is used for energy or synthesis of compounds to support growth, (4) regulates the cellular responses to hypoxia, (5) controls the post-translational modification of hundreds of cell proteins in the mitochondria, cytosol, and nucleus through succinylation, (6) controls critical aspects of transcription, (7) modulates protein signaling within cells, and (8) modulates cellular calcium. The primary focus of this review is to understand how reductions in KGDHC are translated to pathologically important changes that underlie both neurodegeneration and cancer. An understanding of each role is necessary to develop new therapeutic strategies to treat neurodegenerative disease.

Comprehensive Evaluation of 24 Red Raspberry Varieties in Northeast China Based on Nutrition and Taste

Red raspberry is a kind of fruit with high nutritional values. To evaluate the comprehensive quality of 24 red raspberry varieties in Northeast China, physicochemical properties, bioactive compounds and sensory characteristics were measured, followed by principal component analysis (PCA) and cluster analysis (CA). Altogether, eight important property indexes for processing attributes were selected out using PCA, including titratable acidity (TAC), sugar-acid ratio (SAR), pH, length, diameter, weight, sucrose and citric acid. Six individual sugars, including l-rhamnose monohydrate, fructose, glucose, sucrose, maltose and d-trehalose anhydrous, as well as eight organic acids, including oxalic acid, tartaric acid, malic acid, α-ketoglutaric acid, lactic acid, citric acid, fumaric acid and succinic acid, were identified in red raspberry. The two main clusters according to individual sugar, organic acids and SAR indicated that varieties including ‘European red’, ‘DNS9’, ‘Bulgaskc’, ‘Canby’ and ‘Samodiva’ were suitable for fresh-eating or processing to juice or other products directly because they had suitable SAR; other varieties with relatively low SAR were unsuitable for fresh-eating and need to adjust their excessive sour taste during processing.

Bifidobacterium breve MCC1274 Supplementation Increased the Plasma Levels of Metabolites with Potential Anti-Oxidative Activity in APP Knock-In Mice.

We previously reported the effects of a probiotic strain, Bifidobacterium breve MCC1274, in improving cognitive function in preclinical and clinical studies. Recently, we demonstrated that supplementation of this strain led to decreased amyloid-β production, attenuated microglial activation, and suppressed inflammation reaction in the brain of APP knock-in (AppNL-G-F) mice. In this study, we investigated the plasma metabolites to reveal the mechanism of action of this probiotic strain in this Alzheimer's disease (AD)-like model. Three-month-old mice were orally supplemented with B. breve MCC1274 or saline for four months and their plasma metabolites were comprehensively analyzed using CE-FTMS and LC-TOFMS. Principal component analysis showed a significant difference in the plasma metabolites between the probiotic and control groups (PERMANOVA, p = 0.03). The levels of soy isoflavones (e.g., genistein) and indole derivatives of tryptophan (e.g., 5-methoxyindoleacetic acid), metabolites with potent anti-oxidative activities were significantly increased in the probiotic group. Moreover, there were increased levels of glutathione-related metabolites (e.g., glutathione (GSSG)_divalent, ophthalmic acid) and TCA cycle-related metabolites (e.g., 2-Oxoglutaric acid, succinic acid levels) in the probiotic group. Similar alternations were observed in the wild-type mice by the probiotic supplementation. These results suggest that the supplementation of B. breve MCC1274 enhanced the bioavailability of potential anti-oxidative metabolites from the gut and addressed critical gaps in our understanding of the gut-brain axis underlying the mechanisms of the probiotic action of this strain in the improvement of cognitive function.

Red algae industrial residues as a sustainable carbon platform for the co-production of poly-3-hydroxybutyrate and gluconic acid by Halomonas boliviensis.

Polyhydroxyalkanoate (PHA) production using halophilic bacteria has been revisited because less severe operational conditions with respect to sterility can be applied, also alleviating production costs. Halomonas boliviensis was selected because it is a moderate halophile able to grow and attain high poly-3-hydroxybutyrate (P3HB) contents under 5–45 g/L NaCl concentrations, conditions that discourage microbial contamination. Industrial residues of the red alga Gelidium corneum after agar extraction were used as sugar platform to reduce costs associated with the carbon source. These residues still comprise a high carbohydrate content (30–40% w/w) of mainly cellulose, and their hydrolysates can be used as substrates for the bioproduction of value-added products. Preliminary assays using glucose were carried out to determine the best conditions for growth and P3HB production by H. boliviensis in bioreactor fed-batch cultivations. Two strategies were addressed, namely nitrogen or phosphorus limitation, to promote polymer accumulation. Similar P3HB cell contents of 50% (gpolymer/gCDW) and yields Y P3HB/glucose of 0.11–0.15 g polymer/g glucose were attained under both conditions. However, higher specific productivities were reached under P-limitation, and thus, this strategy was adopted in the subsequent study. Two organic acids, resulting from glucose metabolism, were identified to be gluconic and 2-oxoglutaric acid. Reducing the oxygen concentration in the cultivation medium to 5% sat was found to minimize organic acid production and enhance the yield of polymer on sugar to 0.20 gP3HB/gglucose. Finally, fed-batch cultivations using G. corneum hydrolysates as the only C-source achieved an overall volumetric productivity of 0.47 g/(L.h), 40% polymer accumulation, and negligible gluconic acid production.

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.

Effects of pH value on stachydrine biosynthesis of hydroponic Leonurus japonicus and its physiological mechanism

The present study explored the physiological mechanism of the effects of different pH treatments on the growth, physiological characteristics, and stachydrine biosynthesis of Leonurus japonicus to provide references for the cultivation and quality control of L. japonicus. Under hydroponic conditions, different pH treatments(pH 5,6,7,8) were set up. The growth, physiology, and the content of stachydrine and total alkaloids of L. japonicus, as well as the content of key intermediate products in stachydrine biosynthesis pathway(i.e., pyruvic acid, α-ketoglutaric acid, glutamic acid, and ornithine) were monitored to explore the physiological mechanism of the effects of pH on the growth and active components of L. japonicus. The results showed that L. japonicus. could grow normally in the pH 5-8 solution. The pH treatment of neutral acidity was more conducive to the accumulation of photosynthetic pigments and the increase in soluble protein in leaves of L. japonicus. to promote its growth and yield. However, since stachydrine is a nitrogen-containing pyrrolidine alkaloid, its synthesis involves the two key rate-limiting steps of nitrogen addition: reductive ammoniation reaction and Schiff base formation reaction. High pH treatments promote the synthesis and accumulation of substrates and products of the above two reactions, indicating that the alkaline environment can promote the nitrogen addition reaction, thereby promoting the biosynthesis and accumulation of stachydrine.

An overview about the approaches used in the production of alpha-ketoglutaric acid with their applications

Abstract Alpha ketoglutaric acid is a biological compound found naturally in the human body. It plays an important role in the cell metabolism and has a role in various metabolic pathways including Kreb’s cycle, protein metabolism and so on. Keto glutaric acid is chemically prepared from succinic acid and oxalic acid. It is a direct precursor of glutamic acid and triazines. It can be produced by oxidative decarboxylation of isocitrate by isocitrate dehydrogenase. The yeast Yarrowia lipolytica is used as a prospective producer of alpha ketoglutaric acid from ethanol. The capability to synthesize Keto glutaric acid has so far been investigated for many microorganisms such as Pseudomonas fluoroscens , Bacillus subtilis etc. P. fluoroscens have the ability to synthesize a huge amount of alpha ketoglutaric acid in a glycerol medium supplemented with manganese (Mn). The Mangnese has a significant impact on glycerol metabolism resulting in the buildup of alpha ketoglutaric acid. The metabolism of succinate may result in the production of alpha ketoglutarate. Despite its importance in TCA cycle, alpha ketoglutaric acid buildup as an intermediate product of bacterial glucose oxidation. Along with chemical synthesis and microbial fermentation, enzymatic transformation can also be used to produce alpha ketoglutaric acid. Biodiesel waste is considered as cheap and renewable carbon source for the development of alpha ketoglutaric acid. Alpha ketoglutarate is used for kidney disease, intestinal and stomach disorders and many other conditions. It also plays an important role in the food industry as food and nutrient enhancers. The review is covering all the aspects related with the Alpha ketoglutaric acid production, utilization and product recovery.

PSVI-4 Serum Metabolomic Characterization of Birth Weight and Neonatal Nutrient Restriction on Piglet Growth and Development

Abstract The objective was to characterize developmental differences in low birth weight (LBW) and normal birth weight (NBW) piglets with or without nutrient restriction using serum metabolomic profile analysis. After farrowing, 112 piglets were selected as LBW (1.22 ± 0.28 kg) or NBW (1.70 ± 0.27 kg) and were categorized to receive normal nutrition (NN) or restricted nutrition (RN - 6 h/day no suckling) until d 28 when the pigs were weaned onto a common diet until d 56. Blood samples were taken on d 28 and d 56 (n=8 pigs/treatment) and were analyzed using quantitative metabolomics via a combination of direct injection mass spectrometry with a reverse-phase LC-MS/MS custom assay (TMIC prime). Data were normalized using logarithmic transformation and auto-scaling. Partial least squares discriminant analysis (PLS-DA) was carried out to further explore the differential metabolites among the treatments (metaboanalyst.ca) with an integrated enrichment and pathway topography analysis. The results suggest that at d 28, LBW piglets had decreased metabolites associated with fatty acid oxidation, glycolysis and TCA cycle metabolites, and essential amino acids such as valine, leucine, arginine. These indicate a decrease utilization of gluconeogenic, and TCA cycle pathways compared with the NBW group. On d 56, LBW piglets had increased utilization of fatty acids, exhibited by increased production of serum acetoacetate, B-hydroxybutyrate, glycerol, compared with NBW. Additionally, the LBW piglets had decreased glucose utilization, pyruvate, succinate, citrate, a-ketoglutaric acid, and lactate compared with the NBW piglets. Due to low utilization of glycolysis and the TCA cycle, associated amino acids were less in LBW piglets, except for a increased glycerol which may indicate impairments in glucose tolerance. In summary, LBW piglets appear to have more metabolic deficiencies in early life, which is not resolved with nutrition in early life, but may be responsive to a tailored nutritional intervention post-weaning.

PSVIII-B-8 Effects of Habituation to Livestock Trailer and Extended Transportation on Plasma Metabolomic Profiles in Goats

Abstract Goats raised for meat production are often transported long distances. Twelve-month-old male Spanish goats were used to determine the effects of habituation to trailers on plasma metabolomic profiles when transported for long periods. In a split-plot design, 168 goats were separated into two treatment (TRT; whole plot) groups and maintained on two different paddocks. Concentrate supplement was fed to one group inside two livestock trailers (habituated group, H), while the other group received the same quantity of concentrate, but not inside the trailers (non-habituated, NH). Goats were subjected to a 10-hour transportation stress in 4 replicates (n = 21 goats/replicate/TRT) after 4 weeks of habituation period. Blood samples were collected prior to loading (Preload), 20 min after loading (0 h), and at 2, 4, 6, 8, and 10 h of transportation (Time; subplot). A targeted quantitative metabolomics approach was employed to analyze the samples using a combination of direct injection mass spectrometry with a reverse-phase LC–MS/MS custom assay. The data were analyzed using R software. Several amino acids (alanine, serine, glycine, histidine, glutamate, trans-hydroxyproline, asparagine, threonine, methylhistidine, ornithine, proline, leucine, tryptophan) were higher (P &amp;lt; 0.05) in the H group compared to the NH group. Five diacylphosphotidyl cholines, 10 lysophosphotidyl cholines, and several other sphingomyelins were higher (P &amp;lt; 0.05) in the NH group compared to the H group. Butyric acid, propionic acid, alpha-ketoglutaric acid, and beta-hydroxybutyric acid concentrations were lower (P &amp;lt; 0.05) in the NH goats compared to the H goats. In general, amino acid concentrations decreased and acylcarnitine levels increased with transportation time (P&amp;lt;0.05). Habituation to trailers can be beneficial in enhancing stress coping abilities in goats due to higher concentrations of metabolites that support energy homeostasis and antioxidant activities. Fatty acid metabolism may be the main energy pathway in goats during long-distance transportation.

Compounds from human odor induce attraction and landing in female yellow fever mosquitoes (Aedes aegypti)

The female Aedes aegypti mosquito is a vector of many human diseases such as yellow fever, dengue, and Zika. Transmission of these viruses occurs when an infected female mosquito locates a suitable human host, alights, and blood feeds. Aedes aegypti use human-emitted odors, as well as heat and visual cues, for host location. However, none of the previously identified human-produced compounds induce significant orientation and landing on a human host. Here we show that female yellow fever mosquitoes orient to and land on a mixture of compounds identified from human skin rubbings. Using odor collection, extraction, a two-choice, bioassay-guided fractionation, and chemical analysis, we identified mixtures of 2-ketoglutaric acid and L-lactic acid as landing attractants for female Ae. aegypti. The mixture of pyruvic acid and L-lactic acid were also found to be weakly attractive. Using ratio-response assays, we found that the attraction and alighting behaviors of the mosquitoes were directly related to the ratio of these compounds presented on the surface of the glass assay beads, suggesting that these compounds could mediate landing on a human host even at sub-nanogram dosages. The newly identified compounds fill a gap in our knowledge of odor-mediated attraction of Ae. aegypti and may lead to the development of new attractant-based mosquito control tactics.

AKG induces cell apoptosis by inducing reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing PI3K/AKT/mTOR-mediated autophagy in renal cell carcinoma.

Alpha-ketoglutarate (AKG) or 2-oxoglutarate is a key substance in the tricarboxylic acid cycle (TCA) and has been known to play an important role in cancerogenesis and tumor progression. Renal cell carcinoma (RCC) is the most common type of kidney cancer, and it has a high mortality rate. Autophagy is a phenomenon of self-digestion, and its significance in tumor genesis and progression remains debatable. However, the mechanisms underlying how AKG regulates autophagy in RCC remain unknown. Thus, the purpose of this study was to assess the therapeutic efficacy of AKG and its molecular mechanisms. RCC cell lines 786O and ACHN were treated with varying doses of AKG for 24 h. CCK-8, Transwell, and scratch wound healing assays were utilized to evaluate the role of AKG in RCC cells. Autophagy protein and PI3K/AKT/mTOR pathway protein levels were analyzed by Western blot. AKG inhibited the proliferation of RCC cells 786O and ACHN in a dose-dependent manner according to the CCK-8 assay. In addition, flow cytometry and Western blot analysis revealed that AKG dose-dependently triggered apoptosis and autophagy in RCC cells. By promoting cell apoptosis and autophagy, AKG dramatically suppressed tumor growth. Mechanistically, AKG induces autophagy by promoting ROS generation and inhibiting the PI3K/AKT/mTOR pathway. The anti-tumor effect of AKG promotes autophagy in renal cancer cells via mediating ROS-PI3K/Akt/mTOR, and may be used as a potential anticancer drug for kidney cancer.

Dynamic transcriptome and LC-MS/MS analysis revealed the important roles of taurine and glutamine metabolism in response to environmental salinity changes in gills of rainbow trout (Oncorhynchus mykiss)

Recently, the frequent salinity fluctuation has become a growing threat to fishes. However, the dynamic patterns of gene expression in response to salinity changes remain largely unexplored. In the present study, 18 RNA-Seq datasets were generated from gills of rainbow trout at different salinities, including 0 ‰, 6 ‰, 12 ‰, 18 ‰, 24 ‰ and 30 ‰. Based on the strict thresholds, we have identified 63, 1411, 2096, 1031 and 1041 differentially expressed genes in gills of rainbow trout through pairwise comparisons. Additionally, weighted gene co-expression network analysis was performed to construct 18 independent modules with distinct expression patterns. Of them, green and tan modules were found to be tightly related to salinity changes, several hub genes of which are known as the important regulators in taurine and glutamine metabolism. To further investigate their potential roles in response to salinity changes, taurine, glutamine, and their metabolism-related glutamic acid and α-ketoglutaric acid were accurately quantitated using liquid chromatography-tandem mass spectrometry analysis. Results clearly showed that their concentrations were closely associated with salinity changes. These findings suggested that taurine and glutamine play important roles in response to salinity changes in gills of rainbow trout, providing new insights into the molecular mechanism of fishes in salinity adaptation.

Liang-Ge decoction ameliorates acute lung injury in septic model rats through reducing inflammatory response, oxidative stress, apoptosis, and modulating host metabolism.

Liang-Ge decoction (LG) has been used in the treatment of early stage of spesis and can ameliorate sepsis-associated lung injury. However, the mechanism of LG on sepsis-associated lung injury remains unknown. In this study, we established a rat model of sepsis-associated lung injury using the cecal ligation and puncture (CLP) method, and investigated the therapeutic effects of LG on lung injury in rats with sepsis. In addition, the anti-inflammatory, anti-oxidative and anti-apoptotic effects of LG on sepsis-associated lung injury model rats were evaluated. Besides, untargeted metabolomics was used to investigate the regulation of metabolites in rats with sepsis-associated lung injury after LG treatment. Our results showed that LG could decrease the wet/dry (W/D) ratio in lung and the total cell count and total protein concentration in bronchoalveolar lavage fluid (BALF) in septic model rats. Hematoxylin and eosin (HE) staining showed that LG reduced the infiltration of pro-inflammatory cells in lung. In addition, LG treatmment down-regulated the gene and protein expression of pro-inflammatory cytokins in lung tissue and BALF. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were increased and the level of methane dicarboxylic aldehyde (MDA) was decreased in lung tissue homogenate in septic model rats after LG treament. Moreover, the numbers of apoptotic cells in lung were reduced and the activity of lactic dehydrogenase (LDH) in BALF was decreased in septic model rats after LG treament. Untargeted metabolomics analysis showed that LG treatment affected the levels of 23 metabolites in lung in septic model rats such as citric acid, methionine, threonine, alpha-ketoglutaric acid, and inositol, these metabolites were associated with the glycine, serine and threonine metabolism, cysteine and methionine metabolism, inositol phosphate metabolism and citrate cycle (TCA cycle) pathways. In conclusion, our study demonstrated the therapeutic effetcts of LG on sepsis-associated lung injury model rats. Moreover, LG could inhibit the inflammatory response, oxidative stress, apoptosis and regulate metabolites related to glycine, serine and threonine metabolism, cysteine and methionine metabolism, inositol phosphate metabolism and TCA cycle in lung in sepsis-associated lung injury model rats.