Metabolic Biochemistry Research Articles

Impact of Nutritional Status on COVID-19-Induced Olfactory Dysfunction.

Although olfactory dysfunction is one of the most common presenting signs of COVID-19 infection, little is known about which populations are most susceptible. The aim of this study is to evaluate the risk of COVID-19-induced chemosensory dysfunction in malnourished individuals. The N3C database was queried for adults having positive COVID-19 test result, diagnosis of chemosensory dysfunction within 2 weeks of positive test date, and overnutrition or undernutrition (i.e., deficiency or excess of micro- and macronutrients) related diagnoses prior to COVID-19 infection. Individuals previously diagnosed with chemosensory dysfunction were excluded. COVID-19-positive adults without olfactory dysfunction were similarly analyzed. Statistical analysis was performed using odds ratio calculations (95% confidence interval [CI]). Of 3,971,536 patients with COVID-19, 73,211 adults were identified with a diagnosis of undernutrition and 428,747 adults were identified with a diagnosis of overnutrition prior to infection. Of those with undernutrition, 264 (0.36%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. Of those with overnutrition, 2851 (0.66%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. The calculated odds ratio for undernutrition and olfactory dysfunction was 0.731 (p < 0.0001, 95% CI [0.0647, 0.0825]). The calculated odds ratio for overnutrition and olfactory dysfunction was 1.419 (p < 0.0001, 95% CI [1.3359, 1.5081]). Overnutrition may increase the risk of COVID-19-related olfactory dysfunction, while undernutrition may slightly protect. While reasons are unclear, baseline differences in metabolic, inflammatory, and structural biochemistry deserve closer inspection. 3 Laryngoscope, 134:4338-4343, 2024.

Controlling glycolysis to generate characteristic volatile organic compounds of lung cancer cells

Characteristic volatile organic compounds (VOCs) are anticipated to be used for the identification of lung cancer cells. However, to date, consistent biomarkers of VOCs in lung cancer cells have not been obtained through direct comparison between cancer and healthy groups. In this study, we regulated the glycolysis, a common metabolic process in cancer cells, and employed solid phase microextraction gas chromatography mass spectrometry (SPME–GC–MS) combined with untargeted analysis to identify the characteristic VOCs shared by cancer cells. The VOCs released by three types of lung cancer cells (A549, PC-9, NCI-H460) and one normal lung epithelial cell (BEAS-2B) were detected using SPME–GC–MS, both in their resting state and after treatment with glycolysis inhibitors (2-Deoxy-d-glucose, 2-DG/3-Bromopyruvic acid, 3-BrPA). Untargeted analysis methods were employed to compare the VOC profiles between each type of cancer cell and normal cells before and after glycolysis regulation. Our findings revealed that compared to normal cells, the three types of lung cancer cells exhibited three common differential VOCs in their resting state: ethyl propionate, acetoin, and 3-decen-5-one. Furthermore, under glycolysis control, a single common differential VOC—acetoin was identified. Notably, acetoin levels increased by 2.60–3.29-fold in all three lung cancer cell lines upon the application of glycolysis inhibitors while remaining relatively stable in normal cells. To further elucidate the formation mechanism of acetoin, we investigated its production by blocking glutaminolysis. This interdisciplinary approach combining metabolic biochemistry with MS analysis through interventional synthetic VOCs holds great potential for revolutionizing the identification of lung cancer cells and paving the way for novel cytological examination techniques.

Implementation of a lifestyle and life‐skills intervention to prevent weight‐gain and cardiometabolic abnormalities in young people with first‐episode psychosis as part of routine care: The Keeping the Body in Mind program

AbstractObjectivesIn 2013, a cluster‐controlled pilot study found the 12‐week Keeping the Body in Mind (KBIM) lifestyle and life skills intervention was able to prevent weight gain in a small sample of youth experiencing first‐episode psychosis (FEP) with fewer than 4 weeks of antipsychotic exposure. This study aims to evaluate the effectiveness of KBIM as routine care on anthropometry and metabolic biochemistry in a larger sample of youth with FEP across three community mental health services.MethodThis retrospective chart audit was conducted on youth with FEP, prescribed a therapeutic dose of antipsychotic medication, and who engaged with KBIM between 2015 and 2019. Primary outcomes were weight and waist circumference. Secondary outcomes were blood pressure, blood glucose, and blood lipids. Outcomes were collected in at baseline and at 12 weeks. Data on program engagement were obtained from the participant's medical file.ResultsOne‐hundred and eighty‐two people met inclusion criteria, and up to 134 people had baseline and 12‐week data on one or more outcome. Mean number of sessions attended was 11.1 (SD = 7.3). Increases in weight and waist circumference were limited to 1.5 kg (SD = 5.3, t(133) = 3.2, p = .002) and 0.7 cm (SD = 5.8, t(109) = 1.2, p = .23) respectively. Eighty‐one percent of participants did not experience clinically significant weight gain (&gt;7% of baseline weight). There were no significant changes in blood pressure or metabolic biochemistry.ConclusionThe prevention of substantial gains in weight and waist circumference observed in the initial pilot study was maintained with implementation of KBIM as part of routine clinical care for youth with FEP.

Efficiency of protein combinations in diets for Rhamdia quelen: growth, digestive and metabolic biochemistry and nutrient deposition.

This study was conducted to determine the best combination of protein sources in diets for jundiá, based on growth, metabolism, and nutrient deposition. Five protein combinations were tested: casein + fish meal (control), casein + gelatin, casein + albumin, casein + albumin + fish meal, and albumin + fish meal, in diets containing 370 g Kg-1 of crude protein and 13.4 MJ Kg-1 of digestible energy. The fish (9.38 ± 0.12 g) were allocated in a water recirculation system at a density of 3.35 g L-1 per experimental unit and fed until apparent satiety for 40 days with the diets. The fish fed with the control diet had the highest final weight, specific growth rate, protein and feed efficiency ratio, protein retention, and best apparent feed conversion. On the other hand, fish that received casein + albumin and albumin + fish meal diets showed worse results in growth and body protein retention, low trypsin and chymotrypsin activity, and high intestinal amylase activity. Therefore, the combination referred to as control (casein + fish meal) conclusively provides the best rhythm for nutrient digestion and metabolism processes, enabling fish to reach greater growth and retention of body protein with low whole-fish fat content.

Chemical composition of Tithonia diversifolia (Hemsl.) and its effect on growth performance, feed efficiency and metabolic biochemistry of juvenile hybrid tilapia Oreochromis mossambicus × Oreochromis niloticus

The aquaculture due to the high cost and continued shortage of animal protein sources, the development of alternative plant protein sources has been one of the main challenges to establish sustainable aquaculture as economically viable. Objective of this investigation was to determine the chemical composition and effect of Tithonia diversifolia on the growth performance, feed efficiency and metabolic biochemistry of juveniles of Oreochromis mossambicus × Oreochromis niloticus. Five treatments were used: 0% (control), 4, 8, 12 and 16% levels of inclusion of T. diversifolia flour in diet to feed juvenile fish cultured in 15 plastic aquariums at a density of 15 fish/aquarium. The assay lasted eight weeks. The T. diversifolia flour was characterized for showing adequate levels of crude protein (21%), with low crude fat (4.5%) levels, neutral detergent fiber levels: 43.03% and acid detergent fiber: 24.40%. The growth performance presented significant differences (p˂0.05), for weight gain, day average weight gain (DAW), length gain, day average length gain (DAL), specific growth rate (SGR), feed efficiency (FE), protein efficiency ratio (PER) and feed conversion ratio (FCR). In treatment with 16% of inclusion of T. diversifolia flour, values obtained for weight gain, DAW, SGR, FE and PER (15.88 g, 0.28 g. day-1, 2.03 %, 0.34 g.g-1 and 0.98, respectively), which did not differ with the control treatment, highlighting the benefits of T diversifolia flour. The metabolic biochemistry parameters experienced a decrease with the increase of T. diversifolia in diet, where the highest values of triglycerides, cholesterol, and glucose were for the control treatment (p &lt;0.05), while the protein increased to 4% of the flour. T. diversifolia flour presents an adequate balance of nutrients for its chemical composition and amino acids, without causing negative effects on the growth performance, weight-length relationship, feed efficiency, survival and metabolic biochemistry.

Cross-sectional audit assessing the quality of dried bloodspot specimens received by UK metabolic biochemistry laboratories for the biochemical monitoring of individuals with Phenylketonuria.

Sapropterin has been approved as a treatment option for individuals with Phenylketonuria in the United Kingdom. Individuals are assessed as responsive to Sapropterin by a ≥30% reduction in Phenylalanine (Phe) concentrations using dried blood spot (DBS) specimens. DBS quality is critical for accurate and precise measurement of Phe. Currently, UK national guidelines for DBS specimen acceptance do not exist for patient-collected DBS specimens. We adopted evidence-based guidelines for specimen acceptance criteria and retrospectively assessed the impact of introducing these guidelines on specimen rejection rates. Methods: Laboratories were invited to audit the quality of DBS specimens routinely received for Phe monitoring using: (1) existing acceptance/rejection criteria and (2) proposed national guidelines. Ten laboratories audited 2111 specimens from 1094 individuals. Using existing local guidelines, the median rejection rate was 4.0% (IQR 1.5-7.2%). This increased to 21.9% (IQR 10.0-33.0%) using the proposed guidelines. Where reason(s) for rejection were provided (n = 299); 211/299 (70.6%) of DBS specimens were too small or multi-spotted. 380 individuals had more than one sample evaluated; 231/380 (60.8%) provided specimens of acceptable quality, 37/380 (9.7%) consistently provided poor-quality DBS specimens. There is significant variability in the quality of patient-collected DBS specimens. If unacceptable specimens are not rejected, imprecise/inaccurate results will be used in clinical decision making. Using annual workload data for England, this equates to 12,410 incorrect results. Individuals and parents/carers should receive ongoing training in blood collection technique to ensure use of evidence-based acceptability criteria does not cause undue distress from increased sample rejection rates.

UK National audit of the measurement of ammonia.

Severe hyperammonaemia is associated with significant morbidity and mortality. Rapid analysis and reporting of ammonia results is essential to prevent patient harm. The aim was to investigate the laboratory sample acceptance criteria, ammonia analysis and the reporting of ammonia results. A questionnaire was distributed to clinical biochemistry laboratories in the United Kingdom. The results were collated and compared to updated best practice guidelines on hyperammonaemia issued by the Metabolic Biochemistry Network (MetBio.net). Seventy-six laboratories responded to the audit questionnaire. Although 83% laboratories are aware of the updated MetBio.net hyperammonaemia guidelines, most laboratories continue to reject samples for ammonia that are 'too old' for analysis (64%), haemolysed (72%) or not sent on ice (24%). Rapid ammonia analysis is available in 96% laboratories and all laboratories offer ammonia analysis on a 24/7 basis. Nearly all laboratories had implemented critical phoning limits for ammonia. Laboratories are rejecting samples for ammonia analysis that have not been collected/transported in an optimal manner. Laboratories should review their sample acceptance criteria for ammonia and accept all samples in order to avoid delaying the diagnosis and management of hyperammonaemia.

18F-FDG PET/MRI Imaging in a Preclinical Rat Model of Cardiorenal Syndrome—An Exploratory Study

Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.

Polyphenols and Small Phenolic Acids as Cellular Metabolic Regulators.

Polyphenols and representative small phenolic acids and molecules derived from larger constituents are dietary antioxidants from fruits, vegetables and largely other plant-based sources that have ability to scavenge free radicals. What is often neglected in polyphenol metabolism is bioavailability and the role of the gut microbiota (GMB), which has an essential role in health and disease and participates in co-metabolism with the host. The composition of the gut microbiota is in constant flux and is modified by multiple intrinsic and extrinsic factors, including antibiotics. Dietary or other factors are key modulators of the host gut milieu. In this review, we explore the role of polyphenols and select phenolic compounds as metabolic or intrinsic biochemistry regulators and explore this relationship in the context of the microbiota–gut–target organ axis in health and disease.

Implementation of a lifestyle and life-skills intervention to prevent weight-gain and cardiometabolic abnormalities in people with first-episode psychosis: the Keeping the Body in Mind program

IntroductionThe development of obesity and metabolic abnormalities that seed future ill-health occur early with antipsychotic treatment. In 2013, the 12-week Keeping the Body in Mind (KBIM) pilot lifestyle intervention was delivered to a small sample of youth experiencing first-episode psychosis (FEP) with &lt;4 weeks of antipsychotic exposure in a cluster-controlled design. The control group experienced significant increases in weight (mean 7.8kg) and waist circumference (mean 7.1cm) compared to non-significant increases (mean 1.8kg) in the KBIM group.ObjectivesTo evaluate the effect of KBIM as routine care on anthropometry and metabolic biochemistry in a larger sample of youth with FEP across three mental health services.MethodsThis retrospective chart audit was conducted on youth with FEP, prescribed a therapeutic dose of antipsychotic medication, and who engaged with KBIM between 2015 and 2019. Primary outcomes were weight and waist circumference. Secondary outcomes were blood pressure, blood glucose and blood lipids. Outcomes were collected in a pre-post design. Implementation elements were also obtained from the participant’s medical file.ResultsOne-hundred and eighty-two people met inclusion criteria. Follow-up data were available on up to 134 people for individual outcomes. Mean number of sessions attended was 11.1 (SD=7.3). Weight and waist changes were limited to 1.5kg (SD=5.3, t(133)=3.2, p=0.002) and 0.7cm (SD=5.8, t(109)=1.2, p=0.23). Nineteen percent experienced clinically significant weight gain. There were no changes to blood pressure or metabolic biochemistry.ConclusionsThe positive outcomes for weight and waist circumference found in the initial pilot study were maintained with implementation as routine care.DisclosureNo significant relationships.

Potential Effects of Anthocyanin-Rich Roselle (Hibiscus sabdariffa L.) Extract on the Growth, Intestinal Histomorphology, Blood Biochemical Parameters, and the Immune Status of Broiler Chickens.

The potential effects of anthocyanin-rich roselle, Hibiscus sabdariffa L. extract (ARRE) on the growth, carcass traits, intestinal histomorphology, breast muscle composition, blood biochemical parameters, antioxidant activity, and immune status of broiler chickens were evaluated. In the present study, Hibiscus acidified ethanolic extract was reported to have a total anthocyanin content of about 359.3 mg cyanidin 3-glucoside/100 g DW, total polyphenol concentration (TPC) of about 598 mg gallic acid equivalent (GAE)/100 g DW, and total flavonoids (TFs) of about 100 mg quercetin equivalent (QE)/100 g DW. Two-hundred-fifty one-day-old chicks (Ross 308 broiler) (87.85 gm ± 0.32) were randomly allotted to five experimental groups and fed on basal diets supplemented with five levels of ARRE: 0, 50, 100, 200, and 400 mg Kg−1 for 35 days. Dietary ARRE addition did not improve the birds’ growth and carcass traits. Supplemental ARRE increased the n-3 polyunsaturated fatty acids (PUFA) (ω-3) percentage in the breast muscle. Dietary ARRE increased the villous height, and the ARRE100 group raised the villus height to crypt depth ratio. Dietary ARRE increased the immunoexpression of immunoglobulin G (IgG) in the spleen. The serum thyroxine hormone (T4) level was higher in the ARRE200 group. The serum growth hormone level was increased by ARRE addition in a level-dependent manner. According to the broken-line regression analysis, the optimum inclusion level of ARRE was 280 mg Kg−1. All levels of supplemental ARRE decreased the serum triglyceride level. The serum total antioxidant capacity (TAC) was increased in the ARRE100-ARRE400 groups, the serum superoxide dismutase (SOD) level was increased in the ARRE200 group, and the serum malondialdehyde (MDA) level was decreased by increasing the ARRE level. Supplemental ARRE significantly increased the serum levels of lysozymes and IL10. The serum complement 3 (C3) level was increased in ARRE200 and ARRE400 groups. It can be concluded that dietary ARRE addition had many beneficial effects represented by the improvements in the bird’s metabolic functions, blood biochemistry, intestinal morphology, antioxidant activity, immune status, and higher ω-3 content in the breast muscles. However, it had no improving effect on the birds’ growth.

Early Exposure to High-Sucrose Diet Leads to Deteriorated Ovarian Health.

BackgroundThe metabolic syndrome (MetS) is correlated with disorders of the reproductive system, such as the polycystic ovary syndrome (PCOS). While consumption of a diet rich in carbohydrates is linked to the development of MetS, it is still unclear if this diet leads to ovarian dysfunction and PCOS.ObjectivesWe investigated the influence of a high-sucrose diet (HSD) on the ovarian milieu of Wistar rats and studied the correlation between high consumption of sugary drinks and the prevalence of PCOS in women.MethodsWistar rats were given a standard laboratory diet (CTR, 10% sucrose, n = 8) or HSD (HSD, 25% sucrose, n = 8) from postnatal day 21 to 120. Animals were evaluated weekly to calculate food intake, feed efficiency and weight gain. Both onset of puberty and estrous cycle were monitored. Metabolic serum biochemistry, organ morphometry and ovarian histology were performed upon euthanasia. In parallel, a fixed-effects multiple linear regression analysis was performed using data from Brazilian states (459 state-year observations) to test the correlation between the consumption of sugar-sweetened beverages (surrogate for HSD intake) and the prevalence of PCOS (surrogate for ovarian dysfunction).ResultsHSD animals showed increased adipose tissue accumulation, hyperglycaemia and insulin resistance when compared to CTR. Interestingly HSD rats also entered puberty earlier than CTR. Moreover, ovaries from HSD animals had an increased number of atretic antral follicles and cystic follicles, which were correlated with the hypertrophy of periovarian adipocytes. Finally, there was a positive correlation between the intake of sugary drinks and prevalence of PCOS in women of reproductive age.ConclusionsHSD ingestion leads to ovarian dysfunction in rats and could be correlated with PCOS in women, suggesting these alterations could lead to public health issues. Therefore, we reinforce the deleterious impact of HSD to the ovarian system and suggest that the reduction of added sugars intake could be beneficial to ovarian health.

Nutritional Physiology and Biochemistry of Dairy Cattle under the Influence of Heat Stress: Consequences and Opportunities.

Simple SummaryModern dairy cows have elevated internal heat loads caused by high milk production, and the effects of accumulating incremental heat are exacerbated when temperature and humidity increases in the surroundings. To shed this additional heat, cows initiate a variety of adaptive mechanisms including increased respiration rate, panting, sweating, reduced milk yield, vasodilatation, and decreased reproductive performance. Hormonal changes based on reciprocal alterations to the energetic metabolism are particularly accountable for reduced efficiency of the dairy production under the heat stress. As animals experience negative energy balance; glucose, which is also a precursor of milk lactose, becomes the preferential energy fuel. In the absence of proper mitigations, heat stress possesses potential risk of economic losses to dairy sector. Besides physical measures for the timely prediction of the actual heat stress coupled with its proper amelioration, nutritional mitigation strategies should target modulating energetic metabolism and rumen environment.Higher milk yield and prolificacy of the modern dairy cattle requires high metabolism activities to support them. It causes high heat production by the body, which coupled with increasing environmental temperatures results in heat stress (HS). Production, health, and welfare of modern cattle are severely jeopardized due to their low adaptability to hot conditions. Animal activates a variety of physiological, endocrine, and behavioral mechanisms to cope with HS. Traditionally, decreased feed intake is considered as the major factor towards negative energy balance (NEBAL) leading to a decline in milk production. However, reciprocal changes related to insulin; glucose metabolism; failure of adipose mobilization; and skeletal muscle metabolism have appeared to be the major culprits behind HS specific NEBAL. There exists high insulin activity and glucose become preferential energy fuel. Physiological biochemistry of the heat stressed cows is characterized by low-fat reserves derived NEFA (non-esterified fatty acids) response, despite high energy demands. Besides these, physiological and gut-associated changes and poor feeding practices can further compromise the welfare and production of the heat-stressed cows. Better understanding of HS specific nutritional physiology and metabolic biochemistry of the dairy cattle will primarily help to devise practical interventions in this context. Proper assessment of the HS in cattle and thereby applying relevant cooling measures at dairy seems to be the basic mitigation approach. Score of the nutritional strategies be applied in the eve of HS should target supporting physiological responses of abatement and fulfilling the deficiencies possessed, such as water and minerals. Second line of abatement constitutes proper feeding, which could augment metabolic activities and synergizes energy support. The third line of supplemental supports should be directed towards modulating the metabolic (propionates, thiazolidinediones, dietary buffers, probiotics, and fermentates) and antioxidant responses (vitamins). Comprehensive understanding of the energetic metabolism dynamics under the impact of incremental heat load and complete outlook of pros and cons of the dietary ameliorating substances together with the discovery of the newer relevant supplementations constitutes the future avenues in this context.

Quantitative proteomic, physiological and biochemical analysis of cotyledon, embryo, leaf and pod reveals the effects of high temperature and humidity stress on seed vigor formation in soybean

BackgroundSoybean developing seed is susceptible to high temperature and humidity (HTH) stress in the field, resulting in vigor reduction. Actually, the HTH in the field during soybean seed growth and development would also stress the whole plant, especially on leaf and pod, which in turn affect seed growth and development as well as vigor formation through nutrient supply and protection.ResultsIn the present study, using a pair of pre-harvest seed deterioration-sensitive and -resistant cultivars Ningzhen No. 1 and Xiangdou No. 3, the comprehensive effects of HTH stress on seed vigor formation during physiological maturity were investigated by analyzing cotyledon, embryo, leaf, and pod at the levels of protein, ultrastructure, and physiology and biochemistry. There were 247, 179, and 517 differentially abundant proteins (DAPs) identified in cotyledon, embryo, and leaf of cv. Xiangdou No. 3 under HTH stress, while 235, 366, and 479 DAPs were identified in cotyledon, embryo, and leaf of cv. Ningzhen No. 1. Moreover, 120, 144, and 438 DAPs between the two cultivars were identified in cotyledon, embryo, and leaf under HTH stress, respectively. Moreover, 120, 144, and 438 DAPs between the two cultivars were identified in cotyledon, embryo, and leaf under HTH stress, respectively. Most of the DAPs identified were found to be involved in major metabolic pathways and cellular processes, including signal transduction, tricarboxylic acid cycle, fatty acid metabolism, photosynthesis, protein processing, folding and assembly, protein biosynthesis or degradation, plant-pathogen interaction, starch and sucrose metabolism, and oxidative stress response. The HTH stress had less negative effects on metabolic pathways, cell ultrastructure, and physiology and biochemistry in the four organs of Xiangdou No. 3 than in those of Ningzhen No. 1, leading to produce higher vigor seeds in the former.ConclusionHigh seed vigor formation is enhanced by increasing protein biosynthesis and nutrient storage in cotyledon, stronger stability and viability in embryo, more powerful photosynthetic capacity and nutrient supply in leaf, and stronger protection in pod under HTH stress. These results provide comprehensive characteristics of leaf, pod and seed (cotyledon and embryo) under HTH stress, and some of them can be used as selection index in high seed vigor breeding program in soybean.

Lower Serum Magnesium Concentrations are associated With Specific Heavy Drinking Markers, Pro-Inflammatory Response and Early-Stage Alcohol-associated Liver Injury§.

Chronic heavy alcohol intake frequently causes liver inflammation/injury, and altered mineral metabolism may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking, changes in serum magnesium levels and biochemical evidence of liver injury in alcohol-use-disorder (AUD) patients who had no clinical signs or symptoms of liver injury. We also aimed to identify any sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. 114 heavy drinking alcohol-dependent (AD) female and male patients aged 21-65years without clinical manifestations of liver injury, who were admitted to an alcohol treatment program, were grouped by alanine aminotransaminase (ALT) levels: ≤ 40IU/L, as no liver injury (GR.1), and ALT>40IU/L as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic biochemistry results, fatty acid panel, serum magnesium and drinking history data were collected at admission; and study-specific measures were evaluated. In all AD patients, lower magnesium was significantly associated with the heavy drinking marker and heavy drinking days past 90days (HDD90). A lower serum magnesium concentration was observed in AD patients with mild liver injury. Females of both groups had mean levels of magnesium in the deficient range. A clinically significant drop in magnesium levels was observed only in the GR.2 (mild liver injury) male AD patients. Females showed a significant association between low magnesium levels and the ω6:ω3 polyunsaturated fatty acids (PUFAs) ratio. Specific heavy drinking markers showed an association with lower magnesium levels. Low serum magnesium levels are common in subjects with AUD and appear to be associated with the onset of liver injury.

O tutor como agente facilitador no processo de ensino e aprendizagem: uma experiência na disciplina de Bioquímica Metabólica

A tutoria faz parte dos programas acadêmicos oferecidos pela Universidade Federal da Paraíba (UFPB), com objetivo de auxiliar os discentes a partir da implementação de estratégias que facilitem o percurso dos estudantes pelas disciplinas com maiores índices de reprovação e evasão. Este trabalho teve como objetivo avaliar o papel do tutor como agente no processo de ensino e aprendizagem na disciplina de Bioquímica Metabólica, na UFPB. Para tanto, os tutores dessa disciplina aplicaram quatro estudos dirigidos e um jogo didático nas turmas dos períodos letivos 2016.2 (Grupo 1/n= 27) e 2017.1 (Grupo 2/n= 23). O desempenho dos discentes que usufruíram dos recursos didáticos foi satisfatório e significativamente maior do que o grupo que não participou. A partir da avaliação da tutoria pelos discentes por meio de um questionário online, respondeu-se unanimemente que a disciplina de Bioquímica Metabólica precisa ofertar tutores, declarando que os mesmos são facilitadores importantes no processo de ensino e aprendizagem.

1793-P: Dopamine D1 plus D2 Receptor Coactivation Ameliorates Metabolic Syndrome (MS) and Nonalcoholic Fatty Liver Disease (NAFLD) in Mice

The peak in circadian dopaminergic activity at the biological clock area, suprachiasmatic nucleus is diminished in insulin resistant states and daily co-administration of dopamine D1 and D2 receptor agonists to restore this circadian peak of hypothalamic dopaminergic activity reverses this insulin resistance (IR) in genetic animal models of MS. However, the impact of such dopamine D1D2 receptor agonist therapy on NAFLD in an obesogenic animal model of the disease has never been investigated and such was the focus of the present study. C57B6 mice were maintained on a 40% kcal fat and 29% kcal sucrose diet with 5% fructose in the drinking water for 12 weeks and then randomized to daily treatment with bromocriptine (BC, a D2 agonist) (10 mg/kg), SKF38393 (S, a D1 agonist) (10 mg/kg), BC + S, or vehicle (N=7-8/gr) for 3 weeks while maintained on the diet. At the end of treatment, animals were sacrificed for analyses of metabolic parameters and liver biochemistry. D1D2 but neither D1 nor D2 agonist therapy maximally improved IR, obesity, and NAFLD. The D1D2 improvement in NAFLD was associated with reduced hepatic expression of lipogenic, inflammatory, insulin resistance-inducing, and FFA oxidative genes while normalizing antioxidant gene expressions (Table). This study suggests that circadian-timed daily dopamine D1D2 agonist therapy may be a means of treating both type 2 diabetes and NAFLD. Disclosure M. Ezrokhi: Employee; Self; VeroScience LLC. S. Luo: Employee; Self; VeroScience LLC. N. Cominos: Employee; Self; VeroScience LLC. B. Raiche: Employee; Self; VeroScience LLC. M. Gustafson: Employee; Self; VeroScience LLC. A.H. Cincotta: Employee; Self; VeroScience LLC.

Why Is It So Hard to Lose Fat? Because It Has to Get Out through Your Nose! A Lab Based Activity on Oxygen Consumption, Metabolic Equations, and the Futility of Exercise‐Only Weight Loss Plans

Daily physical activity and exercise programs are often thought to be an effective method for overweight individuals to quickly lose substantial fat mass. However, few people have realistic expectations for the amount of exercise‐induced fat loss that can be achieved for the average person. Even fewer understand the biochemistry that occurs in the body when fat is “lost” and where the lost mass has gone. Understanding that fat is “burned” with the help of inhaled oxygen, and most of the mass lost must be exhaled from the body as carbon dioxide might help people have more realistic expectations for weight loss. Therefore, the purpose of this study was to design a lab‐based activity that provided students with a basic understanding of metabolic biochemistry and engaged them with collection of their own data to determine a realistic time scale for exercise‐induced fat loss.Prior to the lab component a brief presentation is given and questions are asked (e.g. “When you lose weight, where does it go? Literally, where is the mass you lost?”) to help students understand the chemistry of the breakdown of fat stores with inhaled oxygen and subsequent carbon dioxide exhalation. Students are tasked with completing 10 minutes worth of exercise, walking or running, on a measured track and at a pace he/she could maintain for one hour. Each student records the distance and time. The relationship of walking and running to physics concepts of work and energy are presented with the concept of “calorie burn” and relationship to oxygen consumption. Metabolic equations that allow calculation of oxygen consumption based on speed of walking or running are introduced. Students calculate the oxygen consumed and calories burned during his/her exercise. Finally, the amount of energy (i.e. calories) in one pound of fat is discussed, and students calculate how long he/she would have had to exercise at the pace walked or run to burn 10 pounds of fat. For a person of average size and fitness, 60+ hours of exercise (1 hour per day, 5 days per week, for 12 weeks) is necessary to burn 10 pounds of fat. A subsequent lab activity using a metabolic cart reinforces these concepts and proves the validity of the calculations used in this activity.This activity has been done with 2 exercise physiology classes (n = 32) with pre‐ and post‐activity follow up questions. Prior to the lab, nearly all students believe exercise is an effective method for most people to lose substantial weight (29/32). Very few students know that fat lost is converted to carbon dioxide and water (2/32). Immediately upon completing the lesson, discovering how long it would take to lose 10 pounds of fat with exercise alone, students are astonished, engaged, and excited to ask follow‐up questions. Long‐term follow‐up indicates the activity was memorable. On end of semester evaluations, a majority of students indicate this was the most memorable laboratory activity (18/32) and the concepts learned in this specific lab were the concepts they were most likely to tell someone about outside of class (19/32). Nearly all students were able to answer the question “Where does fat go when it is ‘lost’?” (30/32) and know that substantial weight loss through exercise alone will take months of dedicated, daily exercise (26/32).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats.

This study evaluated the preventative effects of metformin (Met) on glucocorticoid (GC)-induced osteoporosis in a rat model, compared with alendronate (Aln). Twenty-eight 3-month-old female Sprague-Dawley rats were randomly assigned into four groups: normal control (Ctr), methylprednisolone (MP, 13mg/kg/day, sc, 5days per week), MP plus Aln orally (1mg/kg/day), and MP plus Met orally (200mg/kg/day). After 9weeks, serum bone metabolic biochemistry, bone densitometry and histomorphometry were performed. The GC-induced osteoporosis model was characterized by decreased osteocalcin, increased tartrate-resistant acid phosphatase-5b (TRAP-5b), and decreased bone mineral density (BMD) in the femur and fifth lumbar vertebra (L5). Histomorphometrically, MP significantly decreased trabecular bone volume, decreased bone formation and increased bone resorption in proximal metaphysis, compared with the controls. Aln and Met increased the BMDs of femur (0.305 ± 0.011 vs. 0.280 ± 0.012, P < 0.05; 0.304 ± 0.019 vs. 0.280 ± 0.012, P < 0.05) and L5 (0.399 ± 0.029 vs. 0.358 ± 0.022, P < 0.05; 0.397 ± 0.022 vs. 0.358 ± 0.022, P < 0.05), compared with the model group. Met increased osteocalcin and decreased TRAP-5b, but Aln only decreased TRAP-5b, compared with model group. In histomorphometry of tibial proximal metaphysis, Aln and Met increased trabecular bone volume (39.21 ± 2.46 vs. 30.98 ± 5.83, P < 0.05; 38.97 ± 5.56 vs. 30.98 ± 5.83, P < 0.05), while Met increased the bone formation dynamic parameters and decreased bone resorption dynamic parameters, but Aln just decreased bone resorption dynamic parameters, compared with model group significantly. These findings suggest that metformin prevents GC-induced bone loss by suppressing bone resorption and stimulating bone formation in trabecular bone. The action mode of metformin was different from alendronate, which only suppressed bone resorption.

Effects of saccharicterpenin on antioxidant status and urinary metabolic profile of rats.

Saccharicterpenin is a new green additive agent that is derived from the extract of Theaceae plants and has the ability to improve immunity and meat quality, increase the digestive enzyme activity, and enhance the intestinal development and growth of animals. However, the antioxidant status and systematic changes in metabolic biochemistry associated with saccharicterpenin supplementation in animals are still unknown. This study examined the effects of saccharicterpenin on the antioxidant status and urinary metabolic profile of rats. Sixteen rats were randomly distributed to 2 groups. One group was treated with 400 mg/kg body weight of saccharicterpenin, and the other group was treated with equal amount of saline. Results revealed that saccharicterpenin significantly increased the capacities of anti-hydroxyl radical (13.18%) and anti-superoxide anion (14.36%), the total antioxidant capacity (48.27%), and the activities of total superoxide dismutase (3.68%), catalase (21.52%), glutathione peroxidase (5.83%) and glutathione S-transferase (29.59%) (P < 0.05). By contrast, the contents of malondialdehyde and glutathione were not significantly affected by saccharicterpenin (P > 0.05). Saccharicterpenin supplementation significantly increased the urinary levels of bile acids, ethanol, α-ketoglutarate, and α-hydroxybutyrate but decreased the level of N-acetylglutamate (P < 0.05). In summary, saccharicterpenin can enhance the antioxidant capacity and modulate the metabolism in rats.