Animal Metabolism Research Articles

Determination of marker residues of quinoxaline-1,4-di-N-oxides and its prototype identification by liquid chromatography tandem mass spectrometry

Quinoxaline-1,4-di-N-oxides (QdNOs), such as carbadox, olaquindox, mequindox, quinocetone, etc. are a class of antibacterial drugs. Prototype drugs residues can not be detected due to their rapid metabolism in animals. Quinoxaline-2-carboxylic acid (QCA) and 3-methyl-QCA (MQCA) are their common marker residues, so it has been always a challenge to trace the specific QdNOs drug used in food animal production. Herein, a liquid chromatography tandem mass spectrometry method was developed to determine QCA and MQCA, and meanwhile, the prototype drugs were identified by analyzing bis-desoxy QdNOs metabolites in single ion-pair monitoring mode. The method indicated that the average recoveries for QCA and MQCA were from 90 % to 105 % with relative standard deviations below 10 %, and the limits of quantification were 1.0 μg/kg. The limits of detection of five bis-desoxy QdNOs (qualitative markers) reached 0.5 μg/kg. This new analytical strategy can effectively solve the identification problem of QdNOs drugs in animal-derived food.

Comparison of LC-MS-based methods for the determination of carboxylic acids in animal matrices

Carboxylic acids (CAs) are key players in human and animal metabolism. As they are hardly retained under reversed-phase liquid chromatography (RP-LC) conditions in their native form, derivatization is an option to make them accessible to RP-LC and simultaneously increase their response for mass spectrometric detection. In this work, two RP-LC tandem mass spectrometry-based methods using aniline or 3-nitrophenylhydrazine (3-NPH) as derivatization agents were compared with respect to several factors including completeness of derivatization, apparent recoveries (RAs) in both cow feces and ruminal fluid, and concentrations obtained in feces and ruminal fluid of cows. Anion exchange chromatography coupled to high-resolution mass spectrometry (AIC-HR-MS) served as reference method. Derivatization efficiencies were close to 100% for 3-NPH derivatization but variable (20–100%) and different in solvent solutions and matrix extracts for aniline derivatization. Likewise, average RAs of 13C-labeled short-chain fatty acids as internal standards were around 100% for 3-NPH derivatization but only 45% for aniline derivatization. Quantification of CAs in feces and ruminal fluid of cows initially fed a forage-only diet and then transitioned to a 65% high-grain diet which yielded similar concentrations for 3-NPH derivatization and AIC-HR-MS, but concentrations determined by aniline derivatization were on average five times lower. For these reasons, derivatization with aniline is not recommended for the quantitative analysis of CAs in animal samples.Graphical abstract

The polyketide to fatty acid transition in the evolution of animal lipid metabolism

Animals synthesize simple lipids using a distinct fatty acid synthase (FAS) related to the type I polyketide synthase (PKS) enzymes that produce complex specialized metabolites. The evolutionary origin of the animal FAS and its relationship to the diversity of PKSs remain unclear despite the critical role of lipid synthesis in cellular metabolism. Recently, an animal FAS-like PKS (AFPK) was identified in sacoglossan molluscs. Here, we explore the phylogenetic distribution of AFPKs and other PKS and FAS enzymes across the tree of life. We found AFPKs widely distributed in arthropods and molluscs (>6300 newly described AFPK sequences). The AFPKs form a clade with the animal FAS, providing an evolutionary link bridging the type I PKSs and the animal FAS. We found molluscan AFPK diversification correlated with shell loss, suggesting AFPKs provide a chemical defense. Arthropods have few or no PKSs, but our results indicate AFPKs contributed to their ecological and evolutionary success by facilitating branched hydrocarbon and pheromone biosynthesis. Although animal metabolism is well studied, surprising new metabolic enzyme classes such as AFPKs await discovery.

Cherries with Different Geographical Origins Regulate Neuroprotection in a Photoperiod-Dependent Manner in F344 Rats.

The photoperiod is the main environmental cue that drives seasonal adaptive responses in reproduction, behavior, and metabolism in seasonal animals. Increasing evidence suggests that (poly)phenols contained in fruits can also modulate seasonal rhythms. (Poly)phenol-rich diets are associated with an improvement in cognitive function and neuroprotection due to their anti-inflammatory and antioxidative properties. However, it is unknown whether cherries affect neuroprotection in a photoperiod-dependent manner. To test this, F344 rats were exposed to L6 (6 h light/day), L12 (12 h light/day) and L18 (18 h light/day) photoperiods and fed a standard chow diet supplemented with either a control, lyophilized cherry 1 or cherry 2 with distinctive phenolic hallmarks. Physiological parameters (body weight, eating pattern index (EPI), testosterone, T4/T3) and hypothalamic key genes (Dio2, Dio3, Raldh1 and Ghrh) were strongly regulated by the photoperiod and/or fruit consumption. Importantly, we show for the first time that neurotrophs (Bdnf, Sod1 and Gpx1) in the hippocampus are also regulated by the photoperiod. Furthermore, the consumption of cherry 2, which was richer in total flavonols, but not cherry 1, which was richer in total anthocyanins and flavanols, enhanced neuroprotection in the hippocampus. Our results show that the seasonal consumption of cherry with a specific phenolic composition plays an important role in the hippocampal activation of neuroprotection in a photoperiod-dependent manner.

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows

Abstract Study objectives were to determine the effects of mitoquinol (MitoQ, a mitochondrial-targeted antioxidant) on biomarkers of metabolism and inflammation during acute heat stress (HS). Crossbred barrows [n = 32; 59.0 ± 5.6 kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCon), 2) TN and MitoQ (n = 8; TNMitoQ), 3) HS control (n = 8; HSCon), or 4) HS and MitoQ (n = 8; HSMitoQ). Pigs were acclimated for 6 d to individual pens before study initiation. The trial consisted of two experimental periods (P). During P1 (2 d), pigs were fed ad libitum and housed in TN conditions (20.6 ± 0.8 °C). During P2 (24 h), HSCon and HSMitoQ pigs were exposed to continuous HS (35.2 ± 0.2 °C), while TNCon and TNMitoQ remained in TN conditions. MitoQ (40 mg/d) was orally administered twice daily (0700 and 1800 hours) during P1 and P2. Pigs exposed to HS had increased rectal temperature, skin temperature, and respiration rate (+1.5 °C, +6.8 °C, and +101 breaths per minute, respectively; P < 0.01) compared to their TN counterparts. Acute HS markedly decreased feed intake (FI; 67%; P < 0.01); however, FI tended to be increased in HSMitoQ relative to HSCon pigs (1.5 kg vs. 0.9 kg, respectively; P = 0.08). Heat-stressed pigs lost BW compared to their TN counterparts (−4.7 kg vs. +1.6 kg, respectively; P < 0.01); however, the reduction in BW was attenuated in HSMitoQ compared to HSCon pigs (−3.9 kg vs. −5.5 kg, respectively; P < 0.01). Total gastrointestinal tract weight (empty tissue and luminal contents) was decreased in HS pigs relative to their TN counterparts (6.2 kg vs. 8.6 kg, respectively; P < 0.01). Blood glucose increased in HSMitoQ relative to HSCon pigs (15%; P = 0.04). Circulating non-esterified fatty acids (NEFA) increased in HS compared to TN pigs (P < 0.01), although this difference was disproportionately influenced by elevated NEFA in HSCon relative to HSMitoQ pigs (251 μEq/L vs. 142 μEq/L; P < 0.01). Heat-stressed pigs had decreased circulating insulin relative to their TN counterparts (47%; P = 0.04); however, the insulin:FI ratio tended to increase in HS relative to TN pigs (P = 0.09). Overall, circulating leukocytes were similar across treatments (P > 0.10). Plasma C-reactive protein remained similar among treatments; however, haptoglobin increased in HS relative to TN pigs (48%; P = 0.03). In conclusion, acute HS exposure negatively altered animal performance, inflammation, and metabolism, which were partially ameliorated by MitoQ.

Gas chromatography-mass spectrometry-based quantitative method using tert-butyldimethylsilyl derivatization for plasma levels of free amino acids and related metabolites in Japanese Black cattle.

The quantification of amino acid and related metabolite levels is important for evaluating amino acid metabolism and function in animals. However, a useful quantitative method is not enough. In this study, we developed and validated tert-butyldimethylsilyl derivatization method using gas chromatography-mass spectrometry to quantify plasma levels of free amino acids and related metabolites in Japanese Black cattle. Of the 51 metabolites examined, 24, including 20 amino acids, one amine, and three keto acids, could be quantified. Compared with the trimethylsilyl derivatization method using gas chromatography-mass spectrometry, which has been used for untargeted metabolomic analysis, the present method had higher analytical reliability. This method is advantageous for assessing branched-chain amino acid (BCAA) metabolism because it enables the quantification of not only BCAA levels (valine, leucine, and isoleucine) but also their bioactive metabolite keto acid levels (2-ketoisovaleric acid, 2-ketoisocaproic acid, and 2-keto-3-methylvaleric acid) in the plasma. In addition, this method can quantify the plasma levels of not only tryptophan but also its bioactive metabolites kynurenine and serotonin. These results suggest that this quantitative method has the potential to further our understanding of amino acid metabolic processes and their functions in Japanese Black cattle.

Показатели белкового обмена у жвачных животных при кормлении отходами соевого производства

The article presents the results of a zootechnical analysis of soybean waste (straw and forage waste), used as the main diet for sheep during the active feeding period. It was concluded on the basis of clinical and biochemical parameters of blood that there was an increase in the level of protein metabolism in experimental animals.

Porphyra Polysaccharides Alleviated High‐Carbohydrate Diet‐Induced Growth Retardation, Lipid Deposition, Impairment of Immune and Antioxidant Functions, and Intestinal Morphology in Rabbitfish (Siganus canaliculatus)

Porphyra polysaccharide (PPS), derived from marine red seaweeds of the Porphyra genus, has been reported to improve growth performance, lipid metabolism, and antioxidant capability in animals. The present study investigated the effects of PPS supplementation to a high‐carbohydrate diet on growth performance, lipid metabolism, immunity, antioxidant capacity, intestinal morphology, and microbial composition in rabbitfish (Siganus canaliculatus). Rabbitfish were fed a basal starch diet (BSD, 15% starch) and high‐starch diets (HSD, 25% starch) supplemented with varying levels of PPS (0%, 1.25%, 2.5%, and 5%) for 8 weeks. The results showed that HSD intake significantly decreased body weight and increased hepatosomatic index compared to rabbitfish fed BSD. But all dietary levels of PPS reversed these two indicators of fish fed HSD. In addition, the supplementation of 2.5% and 5% PPS significantly reduced the higher lipid contents in whole fish and abdominal muscle of fish fed HSD. Notably, 2.5% PPS reduced lipid droplets in the liver, possibly through the downregulation of genes associated with lipid synthesis and the upregulation of genes associated with lipid catabolism. Moreover, all levels of PPS supplementation decreased the higher serum alanine aminotransferase activity in fish fed HSD, indicating the alleviation of HSD‐induced liver impairment. Additionally, PPS inclusion significantly increased the activity of serum lysozyme, superoxide dismutase, and catalase while decreasing serum malondialdehyde in fish fed HSD, suggesting improvements in immunity and antioxidant capacity. Furthermore, PPS inclusion mitigated damage to intestinal villi induced by HSD. Interestingly, 2.5% PPS increased the abundance of Bacteroidetes and Tenericutes while reducing the abundance of Proteobacteria and Spirochetes, indicating the reshaping of gut microbiota. In summary, dietary PPS alleviated the negative effects of HSD on growth performance, lipid metabolism, immunity, antioxidant capacity, and intestinal morphology and altered microbial composition in rabbitfish. This highlighted the beneficial effects of dietary PPS in fish and suggested it could contribute to the new strategies for treating metabolic syndrome and health impacts in aquatic animals.

Copper metabolism and its implications for canine nutrition.

Canine copper nutrition has received increased attention due to recent reports of apparent copper-associated hepatitis in the USA and European Union. In order to properly address the need to modify the U.S. National Research Council and Association of American Feed Control Officials canine copper recommendations that will have implications for all dogs, it is important to understand the complexities of copper metabolism, confounding variables affecting copper status, and the available research on this topic in dogs. Recent trends in consumer preference for dog diets, supplements, and functional treats introduce another layer of complexity, as most ingredients used in these formulations provide vastly different proportions of essential nutrients, thus resulting in great variation in nutrient profiles available to the animal. Although controlled research addressing copper metabolism in dogs is limited, there are lessons to be learned from other monogastric species as well as canine case studies that can provide a base for increasing knowledge to address this issue. Copper metabolism and status in animals is affected by a multitude of factors including absorption, storage, excretion, and nutrient interactions. Given its vital role in many physiological processes, it is important that both nutritional deficiencies and toxicities be avoided. Additionally, another challenge for proper copper nutrition in dogs is the known genetic predispositions of some breeds for copper storage and excretion abnormalities. Therefore, it is imperative that veterinarians, nutritionists, and pet food manufacturers collaborate with the shared goal of providing dog food options that supply the essential nutrients at adequate concentrations to support an active and healthy life. Many questions remain regarding copper metabolism and proper diet formulation for dogs. Future research efforts should focus on discovering reliable, non-invasive methods for evaluating canine copper status, a deeper understanding of genetic predispositions of certain breeds, increased knowledge of copper contributions from various ingredients, and the role of unpredictable physiological stressors on copper metabolism.

Conducting biological tests in the development of self-emulsifying drug delivery systems with simvastatin

The aim of the study was to compare the hypolipidemic activity of the developed self-emulsifying drug delivery systems with simvastatin with reference samples of the substance and the finished drug product of industrial production. Materials and methods. The substance of simvastatin (India, s. DK40-2005021, 99.09 %, introduced into the composition of self-emulsifying compositions based on castor oil (Ukraine), polyethylene glycol 40 hydrogenated castor oil (India), Tween 80 (Ukraine), glycerol monostearate (Gustav Heess GmbH, Germany) or polyethylene glycol 100 stearate (ERCA, Italy). Reference samples were Simvastatin-Sandoz (Salutas Pharma, Germany, series LX5161) and simvastatin in pure form. The experimental animals were Syrian hamsters aged 2 months. Hyperlipidemia was modeled by means of an alimentary load. To assess the state of lipid metabolism in animals, the content of triacylglycerols, total cholesterol, low-density lipoprotein and high-density lipoprotein in the blood serum was determined by colorimetric enzymatic methods using the appropriate standard reagent kits "Triacylglycerols F" HP022.02, "Cholesterol F" HP026.02, "Cholesterol-LDL F" HP026.05 and "Cholesterol-HDL F" HP026.04 (LLC SPE "Filicit-Diagnostics", Ukraine) on a semi-automatic biochemical analyzer MapLab Plus (BSI, Italy). Results. The reference samples had similar dose-dependent efficacy parameters. At the same time, the test samples, also having similar dose-dependent effects, in absolute terms at the maximum concentration reduced the amount of low-density lipoprotein and total cholesterol more effectively than the reference samples. When using the test samples in their average concentration, the level of triglycerols was significantly reduced, which is rather a concomitant effect of simvastatin. Conclusions. The improvement of the overall efficacy of simvastatin when it is introduced into self-emulsifying drug delivery systems has been proved, which is associated with the modification of pharmacokinetic parameters by improving the solubility of the substance in the aqueous environment of the gastrointestinal tract

A Nonlinear Dynamical View of Kleiber's Law on the Metabolism of Plants and Animals.

Kleiber's empirical law, which describes that metabolism increases as the mass to the power 3/4, has arguably remained life sciences' enigma since its formal uncovering in 1930. Why is this behavior sustained over many orders of magnitude? There have been quantitative rationalizations put forward for both plants and animals based on realistic mechanisms. However, universality in scaling laws of this kind, like in critical phenomena, has not yet received substantiation. Here, we provide an account, with quantitative reproduction of the available data, of the metabolism for these two biology kingdoms by means of broad arguments based on statistical mechanics and nonlinear dynamics. We consider iterated renormalization group (RG) fixed-point maps that are associated with an extensive generalized (Tsallis) entropy. We find two unique universality classes that satisfy the 3/4 power law. One corresponds to preferential attachment processes-rich gets richer-and the other to critical processes that suppress the effort for motion. We discuss and generalize our findings to other empirical laws that exhibit similar situations, using data based on general but different concepts that form a conjugate pair that gives rise to the same power-law exponents.

EXPLORING THE SYNERGY: ESSENTIAL OILS IN ANIMAL NUTRITION AND THEIR ROLE IN ENHANCING PRODUCTION

Animal nutrition plays a pivotal role in the global livestock industry, influencing production efficiency, animal health, and overall economic sustainability. As a growing awareness of the importance of natural and sustainable practices emerges, essential oils have garnered attention as potential feed additives with multifaceted benefits. This article provides an in-depth exploration of the integration of essential oils into animal nutrition, elucidating their mechanisms of action, effects on animal health, and contributions to enhanced production outcomes. The paper outlies the historical context of essential oil usage in animal nutrition and the objectives of this review. It delves into the chemical composition of essential oils, paving the way for a comprehensive understanding of their role. Mechanisms of action are elucidated, highlighting how essential oils interact with the digestive system and metabolism of animals, ultimately improving nutrient utilization and gut health. These mechanisms are the cornerstone of their potential to enhance production. Beyond their physiological effects, essential oils' impact on animal health is thoroughly examined. A review of relevant studies showcases their effectiveness in preventing and managing common diseases, underscoring their holistic benefits. The article then delves into their tangible effects on production parameters, such as growth rate, feed efficiency, and reproductive performance, drawing insights from case studies and experimental data.
 However, challenges and considerations are not overlooked. The review highlights potential limitations and the need for judicious and evidence-based use of essential oils in animal nutrition. It emphasizes the importance of responsible practices and sustainability in the livestock industry. In conclusion, this review synthesizes the current knowledge surrounding the integration of essential oils into animal nutrition and their profound potential to enhance production outcomes. It underscores the critical role of essential oils as a natural and sustainable approach to optimizing animal nutrition and, by extension, advancing the global livestock industry. The exploration of this synergy paves the way for future research and innovation in this evolving field.

The effect of selenium supplements on selenium metabolism, performance and intestinal microbiome in farm animals (review)

Selenium is one of the most important essential elements for immune function and general health of cattle. The role of selenium in maintaining animal health is primarily based on the functions of selenocysteine-containing proteins, many of which have antioxidant activity. Role of selenium in Animal Health is primarily based on the functions of selenocysteine-containing proteins, many of which possess antioxidant activity. Insufficient selenium intake can be accompanied by subclinical diseases, which leads to a decrease in productivity. It was determined that the inclusion of additional sources of selenium has a significant effect on live weight gain, quality characteristics of meat, as well as the intestinal microbiome in cattle and other types of farm animals (pigs, poultry). However, despite the rather high level of knowledge of the selenium role in the implementation of the functional traits in farm animals, there is still no consensus in the scientific community on the optimal dosages and methods of feeding selenium, which reduces the effectiveness of the use of selenium-containing preparations in practical animal husbandry.

Effects of different chronic restraint stress periods on anxiety- and depression-like behaviors and tryptophan-kynurenine metabolism along the brain-gut axis in C57BL/6N mice

Chronic restraint stress (CRS) is a widely used stimulus to induce anxiety- and depression-like behaviors, linked to alterations in tryptophan-kynurenine (TRP-KYN) metabolism in animals. This study assessed the effects of different CRS periods on anxiety- or depression-like behaviors and TRP-KYN metabolism along brain-gut axis in C57BL/6N mice. Results showed that one-week CRS decreased the open arm entries of mice in elevated plus maze and delayed latency of feeding in novelty suppressed feeding test. Four-week CRS reduced sucrose preference, increases forced swimming immobility time, and also induced anxiety-like behaviors of mice. UPLC-MS/MS analysis revealed decreased levels of the neurotoxic 3-hydroxykynurenine (3-HK) and quinolinic acid (QA), and an increase in the neuroprotective kynurenic acid (KA) in the hippocampus of one-week CRS mice; meanwhile, four-week CRS mice displayed a reduction in KA and increases in 3-HK and QA. In the colon, both one-week and four-week CRS mice exhibited significant reductions in 3-HK and QA, with a marked increase of KA exclusively in four-week CRS mice. Briefly, one-week CRS only induced anxiety-like behaviors with hippocampal neuroprotection in TRP-KYN metabolism, whereas four-week CRS caused anxiety- and depression-like behaviors with neurotoxicity. In the colon, during both CRS periods, KYN was metabolized in the direction of NAD+ production. However, four-week CRS triggered intestinal inflammation risk with increased KA. Summarily, slightly short-term stress has beneficial effects on mice, while prolonged chronic stress can lead to pathological changes. This study offers valuable insights into stress-induced emotional disturbances.

Effect of Injection Vitamin B-Complex on Diet for Consumption, Feed Rate Conversion and Average Daily Weight Gain of Bali Cattle in the Growing Phase

The use of Vitamin B-complex injection is considered more practical, low cost, and easier in the implementation process, and the role of Vitamin B-complex is as a cofactor in the metabolic process and stimulates voluntary consumption. The aim of this study is to find out the effect of injecting different cc (ml) of B-Complex vitamins on diet intake, feed conversion, and average daily weight gain of Bali cattle in the growing phase. This study was carried out in the municipality of Bobonaro, with a duration of 81 days. The experimental method was used with T-test statistics. The independent groups represent two groups of male cattle and each group is composed of 5 male cattle. The groups are called A, and B, therefore, group A receives an injection of Vitamin B-Complex according to the initial weight of each animal, and group B as a control without Vitamin-B-Complex injection. Both groups received the same diet which is composed of Leucaena leucocephala, Gliricydia spium, Panicum maximum, and rice straw (Oryza sativa Lin). The results of the statistical analysis revealed that there was no difference (P>0.05) between the two groups, mainly in dry matter intake, feed conversion, and average daily weight gain. Therefore, the injection of Vitamin B-Complex should be less necessary to promote the growth of ruminant animals, mainly cattle, due to the degradation of the vitamins in the rumen, in addition to the fact that the vitamin acts by competitive inhibition at different points in the metabolism process, in addition to its participation, it is also fundamental in the oxidation of substrates and energy supply in the animal's metabolism process.

Thermosensation and Temperature Preference: From Molecules to Neuronal Circuits in Drosophila.

Temperature has a significant effect on all physiological processes of animals. Suitable temperatures promote responsiveness, movement, metabolism, growth, and reproduction in animals, whereas extreme temperatures can cause injury or even death. Thus, thermosensation is important for survival in all animals. However, mechanisms regulating thermosensation remain unexplored, mostly because of the complexity of mammalian neural circuits. The fruit fly Drosophila melanogaster achieves a desirable body temperature through ambient temperature fluctuations, sunlight exposure, and behavioral strategies. The availability of extensive genetic tools and resources for studying Drosophila have enabled scientists to unravel the mechanisms underlying their temperature preference. Over the past 20 years, Drosophila has become an ideal model for studying temperature-related genes and circuits. This review provides a comprehensive overview of our current understanding of thermosensation and temperature preference in Drosophila. It encompasses various aspects, such as the mechanisms by which flies sense temperature, the effects of internal and external factors on temperature preference, and the adaptive strategies employed by flies in extreme-temperature environments. Understanding the regulating mechanisms of thermosensation and temperature preference in Drosophila can provide fundamental insights into the underlying molecular and neural mechanisms that control body temperature and temperature-related behavioral changes in other animals.

MnO2 nanoparticles trigger hepatic lipotoxicity and mitophagy via mtROS-dependent Hsf1Ser326 phosphorylation

Manganese (Mn) is an essential element for maintaining normal metabolism in vertebrates. Mn dioxide nanoparticles (MnO2 NPs), a novel Mn source, have shown great potentials in biological and biomedical applications due to their distinct physical and chemical properties. However, little is known about potential adverse effects on animal or cellular metabolism. Here, we investigated whether and how dietary MnO2 NPs affect hepatic lipid metabolism in vertebrates. We found that, excessive MnO2 NPs intake increased hepatic and mitochondrial Mn content, promoted hepatic lipotoxic disease and lipogenesis, and inhibited hepatic lipolysis and fatty acid β-oxidation. Moreover, excessive MnO2 NPs intake induced hepatic mitochondrial oxidative stress, damaged mitochondrial function, disrupted mitochondrial dynamics and activated mitophagy. Importantly, we uncovered that mtROS-activated phosphorylation of heat shock factor 1 (Hsf1) at Ser326 residue mediated MnO2 NPs-induced hepatic lipotoxic disease and mitophagy. Mechanistically, MnO2 NPs-induced lipotoxicity and mitophagy were via mtROS-induced phosphorylation and nucleus translocation of Hsf1 and its DNA binding capacity to plin2/dgat1 and bnip3 promoters, respectively. Overall, our findings uncover novel mechanisms by which mtROS-mediated mitochondrial dysfunction and phosphorylation of Hsf1S326 contribute to MnO2 NPs-induced hepatic lipotoxicity and mitophagy, which provide new insights into the effects of metal oxides nanoparticles on hepatotoxicity in vertebrates.

VETERINARY AND SANITARY ASSESSMENT OF THE CONTENT OF TECHNOLOGICALLY HARMFUL SUBSTANCES IN MILK AND THEIR REMOVAL FROM THE ANIMAL BODY

Тhe unfavorable ecological situation in the zones of man-made pollution is due to non-compliance with the requirements for the treatment of plants with toxic chemicals, the uncontrollable excess of emissions from industrial enterprises and motor vehicles, man-made disasters caused by the war of liberation, etc. As a result, particularly toxic substances, compounds of lead, cadmium, mercury, strontium and other heavy metals enter the atmosphere. Heavy metals, which are part of herbicides and fungicides, medicines, fertilizers, plant growth stimulants and poisons for their protection, accumulate in the environment, in particular in feed, enter the atmosphere with combustion products, respectively, have a negative impact on the well-being of animals, quality and safety of livestock products, in particular milk. Therefore, the priority direction, under conditions of increased man-made load on the environment and animals, was and is the monitoring of heavy metals in the trophic chain: soil-plant-feed-animal-product-human. According to a number of authors, a significant amount of toxic substances, including heavy metals that enter the animal's body with feed, water and by air are removed from it through the alimentary canal, kidneys, skin and mammary gland. According to Kovalchuk I.I., Fedoruka R.S. (Kovalchuk, Fedoruk, 2006), the content of heavy metals in the milk of cows under conditions of increased technogenic load on the environment depends on the intensity of harmful emissions, the content of heavy metals in them, the set of fodder in the diet and its balance, as well as the season of keeping, the period of lactation and the level of productivity. Therefore, an important task should be a scientific and practical in-depth study of man-made environmental pollution, which would include various studies of heavy metals, toxic chemicals in soil and feed, means of correcting their impact on the metabolism of productive animals.

Methylation of the leptin gene promoter is associated with a negative correlation between leptin concentration and body fat in Tupaia belangeri

AimsLeptin is a signaling protein secreted by white adipose tissue encoded by the obesity gene, and its main function is to regulate the food intake and energy metabolism in mammals. Previous studies had found that animal leptin concentration was positively correlated with its body fat, but the leptin concentration of Tupaia belangeri was negatively correlated with its body fat mass. The present study attempted to investigate the mechanisms of leptin concentration negatively correlated with its body fat mass in T. belangeri. Material and methodsWe measured the leptin concentration of the two groups of animals by enzyme linked immunosorbent assay (ELISA) and quantified the leptin mRNA expression by qPCR. Then, the histological, transcriptomic, and bisulfite sequencing of the two groups of animals were studied. Moreover, to investigate the energy metabolism under the negative correlation, we also analyzed the metabolomics and metabolic rate in T. belangeri. Key findingsWe revealed the negative correlation was mediated by leptin gene methylation of subcutaneous adipose tissue. Further, we also found that T. belangeri increased energy metabolism with leptin decreased. SignificanceWe challenge the traditional view that leptin concentration was positively correlated with body fat mass, and further revealed its molecular mechanism and energy metabolism strategy. This special leptin secretion mechanism and energy metabolism strategy enriched our understanding of energy metabolism of animals, which provided an opportunity for the clinical transformation of metabolic diseases.

Regulation of hormonal receptors of the hypothalamic-pituitary-gonadal axis by ghrelin in ovary of grass carp (Ctenopharyngodon idella)

Ghrelin has been well known as an orexigenic hormone that regulates appetite and energy metabolism in animals. Recent studies imply the regulatory function of ghrelin on ovary development, however, the mechanism about the effects of ghrelin on key hormonal receptors in ovary is far away from systematically understood. The present study aimed to analyze the tissue distribution of ghrelin and related genes and elucidate the regulation of ghrelin on key hormonal receptors in ovary of grass carp (Ctenopharyngodon idella). High expression of ghrelin and ghrelin O-acyltransferase (GOAT) was found in the ovary compared to heart, kidney, spleen, muscle, brain, liver, gill and intestine. To understand the regulatory function of ghrelin on ovarian development, the effects of ghrelin on the key hormone receptors participated in ovarian maturation were determined by ghrelin, acyl-ghrelin and octanoic acid (substrate in the ghrelin acylation system) treatments with 1, 10 and 100 nM concentration. The in vivo study showed that all the 1, 10 and 100 nM ghrelin treatment stimulated follicle-stimulating hormone receptor (FSHR) expression compared to the control. Estrogen Receptor-α (ERα) was depressed by 10 nM acyl-ghrelin compared to the control, while ERβ1 and ERβ2 could be inhibited by 1 nM and 10 nM octanoic acid treatment compared to the control, respectively. The present results for the first time provided novel information about the regulatory role of ghrelin on key hormonal receptors in ovarian of grass carp providing potential new ideas for cultivating of grass carp broodstock.