Dietary supplementation with ovine serum immunoglobulin is associated with an increased gut luminal mucin concentration in the growing rat

The mucus layer covering the gut epithelium is pivotal to host defence and is affected by various dietary components. Part of the reported beneficial effect of dietary immunoglobulins (Igs) on gut health may be due to effects on the gut mucus layer. The aim was to determine whether orally administered ovine serum Ig influence goblet cell count, mucin gene expression and digesta mucin protein content in the gut of the growing rat. Fourteen Sprague-Dawley male growing rats were used in a 21-day study and were fed either a casein-based control diet (CON; no Ig) or a similar diet but containing freeze-dried ovine Ig (FDOI). Daily food intake and growth rate were not affected by the dietary treatments. When compared to the rats consuming CON diet, those consuming the FDOI diet had significantly (P < 0.05) more intact and cavitated goblet cells in the intestinal villi. A similar result was found for crypt goblet cells in the small intestine and colon. Ileal Muc2, Muc3, Muc4 and stomach Muc5Ac mRNA expressions for the FDOI animals were higher (P < 0.05) compared to the the CON animals. Mucin protein content was higher (P < 0.05) in the stomach, ileum and colonic digesta of rats fed the FDOI diet. In conclusion, orally administered FDOI influenced gut mucins in the growing rat as evidenced by increased mucin gene expression and digesta mucin protein concentrations as well as an increased goblet cell count.     

Dietary supplementation with ovine serum immunoglobulin attenuates acute effects on growth, organ weights, gut morphology and intestinal mucin production in the growing rat challenged with Salmonella enteritidis

The aim was to determine the effect of orally administered ovine serum immunoglobulin (Ig) on growth performance, organ weight, gut morphology and mucin production in the Salmonella enteritidis--gavaged growing rat. Four groups consisted of non-gavaged rats fed a casein-based control basal diet (BD) and three groups of rats gavaged with 1×10(7) CFU S. enteritidis and fed a casein-based diet, a diet containing freeze-dried ovine Ig (FDOI) or a casein-based diet containing inactivated ovine Ig (IOI). The rats were randomly allocated to one of the four groups (n=15/group) and received their respective diets for an 18-day experimental study. Gavaging took place on day 15. Average daily gain and body gain : feed ratio (post-gavage, 3 days) were significantly (P<0.05) higher for the Salmonella-challenged rats fed the FDOI diet compared to those fed the BD and IOI diets. At the end of the study, the small intestine and colon were significantly (P<0.05) heavier for the gavaged rats fed the FDOI diet compared to the gavaged rats fed either the BD or IOI diet. Moreover, the relative weights of the caecum, liver and spleen of the gavaged rats fed the BD or IOI diet were significantly (P<0.05) heavier compared to the gavaged rats fed the FDOI diet. Generally, the gavaged rats fed the FDOI diet had significantly (P<0.05) higher goblet cell counts and luminal mucin protein contents than the gavaged rats fed either the BD or IOI diet and had a more functional gut morphology. Overall, the FDOI fraction prevented the acute effects of S. enteritidis.     

Immunomodulatory effects of ovine serum immunoglobulin in the growing rat

This study aimed to determine whether orally administered ovine serum immunoglobulin (Ig) modulates aspects of immunity such as phagocytosis, lymphocyte proliferation, cytokine production, intestinal and plasma Ig concentrations in growing rats. Forty-five male Sprague-Dawley rats (n = 15/group) were used in the 21-day study, and fed a basal control diet (BD; no Ig) or two test diets: freeze-dried ovine Ig (FDOI) and inactivated ovine Ig (IOI). Phagocytic activity of peripheral blood leukocytes and lymphocyte proliferation in the presence of the mitogen concanavalin A (ConA) was greater (P < 0.05) for the FDOI-fed rats than for the BD- and IOI-fed groups. ConA-stimulated and unstimulated spleen cell culture produced higher (P < 0.05) interferon-γ and interleukin-4, respectively, from rats fed the FDOI than rats fed the BD diet. In the jejunum, ileum and plasma, rats fed FDOI produced higher (P < 0.05) concentrations of secretory IgA (sIgA) than rats fed IOI or BD. Rats fed the FDOI diet had greater jejunal (P = 0.037) and lower plasma (P = 0.025) rat IgG concentrations than rats fed either BD or IOI. In conclusion, an ovine Ig fraction selectively modulated various indices of immune function.     

Comparative effects of exopolysaccharides from lactic acid bacteria and fructo-oligosaccharides on infant gut microbiota tested in an in vitro colonic model with immobilized cells

The aim of this study was to compare the effects of purified exopolysaccharides from Lactobacillus rhamnosus RW-9595M with those of a well-known prebiotic (short-chain fructo-oligosaccharides) on infant colonic microbiota using a new three-stage chemostat model with immobilized infant faecal microbiota. Two continuous cultures with different faecal inocula were tested with different compositions of carbohydrate media. During the first fermentation (F1), fructo-oligosaccharides tested at a concentration of 9.8 g L(-1) increased the number of lactobacilli and decreased coliforms both in gel beads and in effluent from all three reactors, in agreement with data from the literature. During the second fermentation (F2), the effect of fructo-oligosaccharides tested at a lower concentration (7.5 g L(-1)) was reduced compared with F1. Fructo-oligosaccharides also increased total organic acid concentration and decreased ammonia production. Results obtained for exopolysaccharide tested at 1.5 g L(-1) indicate that exopolysaccharides from L. rhamnosus RW-9595M was not metabolized by infant microbiota and lacked any prebiotic effect.     

Effects of alginates on the ingestion and excretion of cholesterol in the rat

The effects of three forms of alginate (free acid, sodium and calcium salts) on ingestion and excretion of cholesterol in the rat were studied. For two weeks, Male Sprague-Dawley rats were fed a cholesterol-rich diet containing 3% alginate from the brown alga Ascophyllum nodosum. The food efficiency of the three types of alginate was: Na-alginate > Ca-alginate > alginic acid. A significant increase in the weight of cecum was also observed in alginate diets. Alginate was not effective in preventing the elevation of serum total cholesterol levels, although irregularly changing patterns were observed. The cholesterol level of liver showed a tendency to decrease with alginate feeding, while fecal excretion of cholesterol increased.     

The effects of short-term fluoride ingestion on bone formation and resorption in the rat femur

Summary The femurs from rats given 120 ppm fluoride in their drinking water for 4 weeks were examined with histological, histochemical, and radiographic methods. Blood removed from the rats prior to sacrifice was analyzed for calcium, phosphorus, and alkaline phosphatase. Results of this study indicated that the ingestion of fluoride produced wide osteoid seams on the periosteal surface of the femoral diaphysis within 4 weeks. The increase in osteoid appeared to be due to an increase in the number of osteoid-producing cells (osteoblasts) along with a subsequent delay in the mineralization of this tissue. The metabolic activity of osteoblasts did not appear to be affected since the intracellular production of acid and alkaline phosphatase was not inhibited. However, due to the high concentration of fluoride ingested, abnormal collagen deposition and a change in bone mineral may have combined to cause a delay in osteoid mineralization. Mineralization was also delayed in the distal femoral epiphyseal plate resulting in an increase in the number of hypertrophied cells. Resorption of metaphyseal trabecular bone, presumably formed prior to fluoride administration, was increased causing a reduction in the amount of trabeculae extending into the shaft of the femur. Concurrent with these changes in bone, the serum levels of calcium, phosphorus, and alkaline phosphatase remained within normal ranges.     

IgA肾病与膜性肾病患者肠道微生物菌群结构分析

【背景】越来越多的证据表明肠道失衡与免疫介导的疾病相关,但肠道菌群和免疫介导的肾脏疾病之间的关系仍不清楚。【目的】通过Illumina高通量测序方法对IgA肾病(immunoglobulin A nephropathy, IgAN)、膜性肾病(membranous nephropathy, MN)患者和健康人群的肠道菌群进行比较。【方法】回顾性选择2020年9月–2021年12月期间,在甘肃省人民医院肾内科行肾穿刺活检并诊断为IgAN及MN患者的新鲜粪便标本,分别编号为IgAN组和MN组,收集体检中心健康人群粪便标本作为健康对照组,每组样本为10例。采用高通量测序技术对粪便样本中所有细菌的16S rRNA基因V3-V4区进行DNA测序,然后进行分类操作单元(operational taxonomic units, OTU)、物种分类、α多样性、β多样性等分析,比较3组之间的肠道菌群差异。【结果】与健康对照组相比,门水平上IgAN组的变形菌门(Proteobacteria)和放线菌门(Actinobacteria)比例明显增高,分别为18%vs. 4%和18.3%vs. 5%;属水平上I...     

Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL particles in the rat

We previously established that proteinuria alters the apolipoprotein content of lipoproteins. This study was conducted to establish whether proteinuria also alters the concentrations of oxidized lipids within lipoprotein density fractions. To this end, we induced passive Heymann nephritis in Sprague Dawley rats and measured an array of alkaline-stable oxylipids in VLDL, LDL, and HDL particles. Proteinuria increased the total oxylipid amounts in the HDL and VLDL fractions. More importantly, these levels were increased when expressed per unit lipoprotein protein, indicating that the oxidized lipid load per particle was increased. Epoxides and diols increased approximately 2-fold in HDL and approximately 5-fold in VLDL, whereas LDL showed approximately 2-fold decreases. The hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids (HODEs) increased >4-fold in HDL and >20-fold in VLDL, whereas LDL showed approximately 2-fold decreases in the HODEs. Therefore, nephrotic syndrome alters the lipoprotein oxylipid composition independently of an increase in total lipoprotein levels. These proteinuria-induced changes may be associated with the cardiovascular risk of lipoprotein oxidation.     

Purification, properties and extended solution structure of the complex formed between human immunoglobulin A1 and human serum albumin by scattering and ultracentrifugation

Immunoglobulin A (IgA) is unique amongst antibodies in being able to form polymeric structures that may possess important functions in the pathology of specific diseases. IgA also forms complexes with other plasma proteins, the IgA1-human serum albumin (HSA) complex (IgA1-HSA) being typical. We have purified this complex using a novel two-step purification based on thiophilic chromatography and gel filtration, and characterised this. HSA is linked covalently to the tailpiece of IgA1 by a disulphide bond between Cys471 in IgA1 and Cys34 in HSA. IgA1-HSA binds to IgA receptors on neutrophils and monocytes, and elicits a respiratory burst that is comparable in magnitude to that of monomeric IgA1. The solution arrangement of IgA1-HSA was identified by X-ray scattering and ultracentrifugation. The radius of gyration R(G) of 7.5(+/-0.3) nm showed that IgA1-HSA is more extended in solution than IgA1 (R(G) of 6.1-6.2 nm). Its distance distribution function P(r) showed two peaks that indicated a well-separated solution structure similar to that for IgA1, and a maximum dimension of 25 nm, which is greater than that of 21 nm for IgA1. Sedimentation equilibrium showed that the IgA1:HSA stoichiometry is 1:1. Sedimentation velocity resulted in a sedimentation coefficient of 6.4S and a frictional ratio of 1.87, which is greater than that of 1.56 for IgA1. The constrained modelling of the IgA1-HSA structure using known structures for IgA1 and HSA generated 2432 conformationally randomised models of which 52 gave good scattering fits. The HSA structure was located at the base of the Fc fragment in IgA1 in an extended arrangement. Such a structure accounts for the functional activity of IgA1-HSA, and supports our previous modelling analysis of the IgA1 solution structure. The IgA1-HSA complex may suggest the potential for creating a new class of targeted therapeutic reagents based on the coupling of IgA1 to carrier proteins.     

生理盐水实验性干预对肉鸡盲肠微生物区系和短链脂肪酸含量的影响

目的研究生理盐水实验性干预对肉鸡盲肠微生物区系和短链脂肪酸含量的影响,以期为早期菌群干预实验的研究提供一定的理论依据。方法选取80只初出壳的小鸡,随机分为2组,分别为对照组(C组)和生理盐水组(S组)。出壳后前2 d,连续每天给S组小鸡灌服0.5 mL灭菌的生理盐水,C组不做处理。第3天,第7天于两组分别随机挑选8只鸡,测定其体重后屠宰取其盲肠内容物,采用Illumina Miseq高通量测序技术对盲肠内容物菌群结构进行测定,并用气相色谱法测定盲肠内容物中短链脂肪酸的含量。结果生理盐水实验性干预对肉鸡早期阶段的平均日增重无显著影响(P>0.05)。在门的水平上,两组肉鸡盲肠菌群占比基本相似,厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)和拟杆菌门(Bacteroidetes)为早期肉鸡肠道内的优势菌门。在属的水平,3日龄时S组肉鸡盲肠中拟杆菌属(Bacteroides)和蓝细菌属(Cyanobacteria_norank)的相对丰度较C组分别提高了160%和143%(P<0.05);7日龄时,两组间盲肠菌属的相对丰度无显著差异。此外,生理盐水实验性干预可极显著降低3日龄肉鸡盲肠内容物中乙酸、丁酸和异戊酸的含量(P<0.01),但7日龄时两组肉鸡盲肠内容物中短链脂肪酸的含量无显著差异(P>0.05)。结论生理盐水实验性干预会对3日龄肉鸡盲肠菌群结构及短链脂肪酸含量产生一定的影响,但这种影响不具有持续性,随着日龄的增加会逐渐消失。     

Effect of Vibrio cholerae non-O1 protease on lysozyme, lactoferrin and secretory immunoglobulin A

Abstract The effect of Vibrio cholerae non-O1 protease on host defense proteins (lysozyme, secretory immunoglobullin A and lactoferrin) was studied in relation to its virulence mechanism. The proteins treated with the protease were analysed by SDS-PAGE. There was no influence of the protease on lysozyme. The protease cleaved lactoferrin into two fragments of 50 kDa and 34 kDa. N-terminal amino acid sequencing of these fragments revealed that the cleavage site was near the hinge region, between serine 420 and serine 421. This cleavage could affect the transition from open to closed configuration which is involved in iron binding and release. The anti-bacterial activity of lactoferrin was not affected by protease treatment. Secretory immunoglobulin A yielded a 42-kDa protein as the cleavage product. The susceptibility of secretory immunoglobulin A to V. cholerae non-O1 protease suggests a mechanism by which bacteria might evade the effect of this immunoglobulin.     

Valproyl-CoA and esterified valproic acid are not found in brains of rats treated with valproic acid,but the brain concentrations of CoA and acetyl-CoA are altered

Sodium valproate and lithium are used to treat bipolar disorder. In rats, both reduce the turnover of arachidonic acid in several brain phospholipids, suggesting that arachidonate turnover is a common target of action of these mood stabilizers. However, the mechanisms by which these drugs reduce arachidonate turnover in brain are not the same. Lithium decreases turnover by reducing the activity and expression of the 85-kDa type IVA cytosolic phospholipase A₂ (cPLA₂); valproate does not affect cPLA₂ activity or expression. To test whether valproate alters neural membrane order by direct esterification into phospholipid or by interrupting intermediary CoA metabolism, we measured valproyl-CoA, esterified valproate, and short chain acyl-CoAs in brains from control rats and rats treated chronically with sodium valproate. Valproyl-CoA and esterified forms of valproate were not found in brain with detection limits of 25 and 37.5 pmol/g brain^–1, respectively. Valproate treatment did result in a 1.4-fold decrease and 1.5-fold increase in the brain concentrations of free CoA and acetyl-CoA when compared to control. Therefore the reduction of brain arachidonic acid turnover by chronic valproate in rats is not related to the formation of valproyl-CoA or esterified valproate, but may involve changes in the intermediary metabolism of CoA and short chain acyl-CoA.     

热休克蛋白90参与糖皮质激素及其受体对气道黏蛋白5AC表达调控的机制

目的:探讨热休克蛋白90(HSP90)在糖皮质激素(GC)信号通路中的作用及其对气道黏蛋白(MUC)5AC表达的调控机制。方法:体外培养气道上皮细胞株BEAS-2B,给予HSP90特异性阻断剂格尔德霉素(GA)和地塞米松(DEX)刺激,比较各组MUC5AC的含量,糖皮质激素受体(GR)的核蛋白表达和GR结合活性。结果:与对照组相比,DEX组的MUC5AC mRNA和蛋白水平降低,伴GR核蛋白水平增高(P0.05);与DEX组相比,GA+DEX组MUC5AC mRNA和蛋白水平升高,GR核蛋白水平降低。放射配体结合实验显示,与对照组相比,GA组的受体最大结合容量(Bmax)降低,平衡解离常数(Kd)升高。结论:HSP90可参与GC及GR的抗气道黏液高分泌效应,其抑制剂可阻断上述效应,该效应是通过降低GR的结合活性来调控的。     

PFG-NMR diffusometry: a tool for investigating the structure and dynamics of noncommercial purified pig gastric mucin in a wide range of concentrations

For the first time, Pulsed Field Gradient-Nuclear Magnetic Resonance, a powerful noninvasive tool for studying the dynamics and structure of complex gels, has been used to measure diffusion of probe molecules in aqueous solutions/gels of noncommercial purified pig gastric mucin (PGM), in a concentration range up to 5 wt %. Complementary data were obtained from rheology measurements. The combination of techniques revealed a strong pH dependency of the structure of the PGM samples while changes in concentration, ionic strength, and temperature appeared to induce less pronounced alterations. Viscosity was found to vary in a nonmonotonous way with pH, with the more viscous solutions found at intermediate pH. We propose that this finding is due to a reduced charge density at lower pH, which is expected to continuously increase the relative importance of hydrophobic associations. The results suggest a loose network of expanded fully charged PGM molecules with considerable mobility at neutral pH (pH 7.4). At intermediate pH (pH 4), a three-dimensional expanded network is favored. At pH 1, the charge density is low and microphase separation occurs since hydrophobic associations prevail. This leads to the formation of clusters concentrated in PGM molecules separated by regions depleted in PGM. The results obtained increase our knowledge about the gastric mucosal layer, which in vivo contains mucin in the same concentration range as that of the samples investigated here.     

Changes in nucleotide concentrations in the erythrocytes of man, rabbit and rat during short-term storage

The $\text{ATP}\text{ADP}$ ratio, measured by high performance liquid chromatography, has been used as an indicator of stability of erythrocyte nucleotides. The nucleotides from human, rabbit and rat whole blood, but not separated erythrocytes were stable for maximum periods of 40, 20 and 15 min respectively after venepuncture. The ratios then declined rapidly from 9 to 5, 12 to 4 and 9 to 1 respectively during 2h storage at room temperature. Similar changes occurred in $\text{GTP}\text{GDP}$ ratios. The relevance of these observations to metabolic studies in intact cells, nucleotide analyses in the clinical situation and comparative studies in other species is discussed.     

Urinary and fecal immunoglobulin A, cortisol and 11-17 dioxoandrostanes, and serum cortisol in metabolic cage housed female cynomolgus monkeys (Macaca fascicularis)

BACKGROUND AND METHODS: Quantitative enzyme-immunoassays of urinary and fecal immunoglobulin A (IgA), cortisol and 11-17-dioxoandrostanes (11,17-DOA), and serum cortisol in eight metabolic-cage-housed female cynomolgus monkeys were performed. The monkeys were divided into two groups, B and NB. Group B animals were blood sampled every 6 hours, whereas Group NB animals were not handled/blood sampled. RESULTS: No differences were recorded between the amounts of feces and urine excreted by the two groups. Group B animals excreted more urinary cortisol than did Group NB animals indicating that restraint-blood sampling resulted in a stress response. Excreted amounts of IgA and 11,17-DOA (urine and feces) did not differ between the groups. CONCLUSIONS: Urinary cortisol was a reliable marker of the stress associated with repeated blood sampling. Declining amounts of excreted urinary cortisol indicated that cynomolgus monkeys acclimated quickly to repeated blood sampling in metabolism cages. Within and between animal variation in amounts of feces voided demonstrated the importance of expressing fecal markers as 'amounts excreted per time unit per kg body weight' rather than just measuring the concentrations in fecal samples.     

Exploring variation in binding of Protein A and Protein G to immunoglobulin type G by isothermal titration calorimetry

Bacterial Protein A (PrtA) and Protein G (PrtG) are widely used for affinity purification of antibodies. An understanding of how PrtA and PrtG bind to different isotypes of immunoglobulin type G (IgG) and to their corresponding Fc fragments is essential for the development of PrtA and PrtG mimetic ligands and for the establishment of generic processes for the purification of various antibodies. In this paper, the interactions between the two IgG-binding proteins and IgG of two different subclasses, IgG1 and IgG4, as well as their analogous Fc fragments have been studied by isothermal titration calorimetry. The results indicate that both protein ligands bind IgG and Fc fragments strongly with Ka values in the range of 10(7) -10(8) M(-1) and for both ligands, the interaction with both IgG isotypes is enthalpically driven though entropically unfavorable. Moreover, variation in the standard entropic and standard enthalpic contribution to binding between the two isotypes as well as between IgG and Fc fragment implies that the specific interaction with PrtA varies according to IgG isotype. In contrast to PrtA, PrtG bound to F(ab')(2) fragment with a Ka value of 5.1 × 10(5) M(-1) ; thus underscoring the usefulness of PrtA as a preferred ligand for generic antibody purification processes.     

Aspirin changes the secretion rate and amino acid composition of human small intestinal mucin in subjects with ileal conduits

The effect of aspirin on the rate of secretion and amino acid composition of human ileal mucin was studied, using subjects with ileal conduits as a model system in which mucin secreted from the ileal conduit tissue is flushed out in the urine and can be measured and analysed. Aspirin (600 mg per day, administered orally) increased the daily mucin output by 37–104% in subjects by days 3 or 4, but thereafter the mucin output declined to below the baseline level by day 10. Mucin samples, purified from the ileal conduit urine during the control period and during aspirin administration, were compared. There were no discernible changes in the degree of polymerisation or the density, but during aspirin administration the amino acid composition was significantly changed, and in particular threonine and proline were enriched. One possible explanation, consistent with the compositional analyses, is that the N- and C-terminal regions of the mucin subunits have been cleaved off and lost during aspirin administration. The observed changes in mucin secretion may have implications for the mechanism of the toxic effects of aspirin on the small intestine by altering the barrier properties of the mucus layer.Abbreviations EGF epidermal growth factor - NSAID non-steroidal anti-inflammatory drug     

The effects of cobalt and iodine supplementation of the pregnant ewe diet on immunoglobulin G, vitamin E, T3 and T4 levels in the progeny

Sixty twin-bearing ewes were allocated to one of four dietary treatments investigating the effects of supplementary iodine or cobalt during late pregnancy on lamb serum immunoglobulin G (IgG), triiodothyronine (T3), thyroxine (T4) and vitamin E concentrations, and lamb IgG absorption efficiency. Ewes were offered grass silage ad libitum supplemented with 800 g per ewe per day of a 190 g/kg crude protein (CP) concentrate from day 126 of gestation until parturition plus one of the following supplements (n = 15 per treatment); no supplement (C); 26.6 mg iodine per day for final 3 weeks pre partum (I-3); 26.6 mg iodine/day for final week pre partum (I-1); 20 mg cobalt/day for final 3 weeks pre partum (Co-3). Lambs were blood sampled at 24 and 72 h post partum for serum IgG and vitamin E concentrations. Ten lambs from C and I-3 were blood sampled at 1 h post partum for serum IgG, vitamin E, T3 and T4 concentrations. There were no differences in serum IgG, vitamin E or T4 values (P > 0.05) at 1 h post partum between lambs born to the C and I-3 ewes. T3 levels were lower in I-3 compared with C progeny (P < 0.05). Supplemental iodine reduced colostral IgG absorption efficiency (P < 0.001) and lamb serum IgG concentrations at 24 and 72 h post partum (P < 0.001). Serum vitamin E concentration in I-3 and I-1 lambs was lower than in Co-3 lambs at 24 h post partum, while at 72 h post partum I-3, I-1 and Co-3 lambs had significantly lower concentrations than C lambs (P < 0.001). Supplementing the ewe's diet with 26.6 mg/day of iodine for the final week of pregnancy reduced lamb serum IgG concentration at 24 and 72 h post partum. The lower total and free T3 values in the progeny of I-3-treated ewes suggest interference in the synthesis and metabolism of thyroid hormones when ewes receive excessive dietary iodine for 3 weeks immediately pre partum. Based on these findings, the indications are that the toxicity level for iodine in the diet of the pregnant ewe should be lowered to 20 mg per ewe per day, equivalent to 40% of its current level. The finding that high-level cobalt supplementation during the final 3 weeks of pregnancy will have a negative effect on serum vitamin E concentration at 72 h post partum is a new and significant finding and previously has not been reported in the literature.     

The effect of acute and prolonged ethanol treatment on the concentrations of coenzyme A, carnitine and their derivatives in rat liver

1. CoA, acetyl-CoA, long-chain acyl-CoA, carnitine, acetylcarnitine and long-chain acylcarnitine were measured in rat liver under various conditions. 2. Starvation caused an increase in the contents of these intermediates, except that of carnitine. 3. A single dose of ethanol had no effect on CoA content, whereas those of acetyl-CoA, acetylcarnitine and carnitine were increased and those of long-chain acyl-CoA and acylcarnitine were decreased. 4. Four weeks' adaptation to ethanol consumption did not change the effect of ethanol administration on these metabolites. 5. It is suggested that ethanol directly increases hepatic fatty acid synthesis and esterification. It is also suggested that this change is reversible and limited to the period of ethanol oxidation. 6. It is demonstrated that ethanol-induced triglyceride accumulation is not related to carnitine deficiency.