Decreases in serum apolipoprotein B-100 and A-I concentrations in cows with milk fever and downer cows

Milk fever occurring during the peripartum period has been suggested to be caused by fatty liver developed during the nonlactating stage because diseased cows have increased serum concentrations of non-esterified fatty acids (NEFA) and show hepatic lipidosis. In cows with fatty liver and related diseases such as ketosis, serum concentrations of apolipoprotein (apo) B-100 and apoA-I are decreased. The purpose of the present study was to examine whether apoB-100 and apoA-I concentrations are similarly decreased in cows with milk fever. Apolipoprotein concentrations were also measured in cows with downer syndrome, which has been suggested to be related, at least in part, to milk fever. Compared with healthy cows during early lactation, apoB-100 and apoA-I concentrations were decreased in cows with milk fever and also in downer cows. In cows with milk fever, the decreases in apoB-100 and apoA-I concentrations were associated with increased NEFA and decreased cholesterol and phospholipid concentrations. However, in downer cows, serum lipid concentration changes were not as distinct as in cows with milk fever. These results, coupled with previous findings on the decreases in apoB-100 and apoA-I concentrations of cows with fatty liver-related diseases, suggest that fatty liver is involved in the development of milk fever and partly in that of downer cow syndrome.     

Determination of Bovine Serum Low-density Lipoprotein Cholesterol using the N-geneous Method

The N-geneous method is a recently developed method for determination of low-density lipoprotein cholesterol (LDL-C) in human serum. In the present study, we attempted to adapt this method to bovine serum. The values of LDL-C obtained using the N-geneous method were highly correlated with those from the method using ultracentrifugation and heparin sepharose affinity chromatography (r = 0.934, p < 0.001). The reproducibility of this method was acceptable (intra-assay CV 4.2%, inter-assay CV 7.6%) for clinical use. Using the N-geneous method, serum LDL-C was evaluated in cows around parturition, and in cows with fatty liver induced by fasting. The concentration of LDL-C decreased significantly in cows close to parturition. A reduced concentration of LDL-C was also observed in cows with fatty liver. In both cases, the changes of LDL-C were similar to those of apolipoprotein B (apoB)-100, and the values of LDL-C were highly correlated (r = 0.876, p < 0.001) with those of apoB-100. These results suggest that the concentration of LDL-C reflects the level of apoB-100. The N-geneous method is simple and rapid, and might to be a useful tool to elucidate the clinical significance of LDL-C in bovine serum.     

Concentrations of apolipoprotein C-III in healthy cows during the peripartum period and cows with milk fever.

Apolipoprotein (apo) C-III is a low-molecular-mass protein mainly distributed in the high-density lipoprotein fraction in cattle serum. We have recently shown that the apoC-III concentration is decreased in cows with fatty liver, ketosis, left displacement of the abomasum, retained placenta and milk fever. The decrease was most distinct in milk fever, thereby suggesting that apoC-III is particularly relevant to the development of milk fever and also that apoC-III is a candidate diagnostic marker for this disease. The purpose of the present study was to examine whether the apoC-III concentration in healthy cows is altered during the peripartum period, to assess the usefulness of apoC-III as a marker for milk fever. ApoC-III concentrations in 17 cows were monitored during the peripartum period (-48 to +12 days from parturition). Of the 17 cows, 14 were apparently healthy during the period. The apoC-III concentrations in the 14 healthy cows were unaltered during the period from -48 to -21 days, but thereafter showed individual variations. Compared with values during the period from -48 to -21 days, the apoC-III concentration was increased (137%) in 5 cows during the period from +1 to +12 days, whereas it decreased (60.7%) in 9 cows. Three cows suffered from milk fever at -3 to +10 days. Decreased apoC-III concentrations in diseased cows (15 to 37% of controls) were more distinct than in the 9 healthy cows. The apoC-III concentration was correlated with lecithin:cholesterol acyltransferase activity in cows with milk fever, but not in healthy cows. Correlation analysis also indicated that apoC-III and apoB-100 concentrations were negatively correlated in 5 healthy cows with increased apoC-III concentrations, but positively in 9 healthy cows with decreased concentrations and cows with milk fever. Determination of the apoC-III concentration during the peripartum period is suggested to be helpful in diagnosing milk fever. The possible relevance of apoC-III and apoB-100 in the development of milk fever is also implied.     

Decreases of apolipoprotein B-100 and A-I concentrations and induction of haptoglobin and serum amyloid A in nonfed calves

Reduced feed intake near parturition is suggested to be one of the major causal factors for the development of fatty liver in cows, and nonfeeding has been used as an experimental model for fatty liver. In cows with fatty liver, concentrations of lipoprotein lipids and proteins are decreased. In addition, the acute-phase protein haptoglobin is induced. The purpose of the present study was to examine whether the decrease of lipoprotein concentrations and the induction of acute-phase proteins were similarly reproduced by non-feeding. Holstein female calves (n=5) were nonfed for 3 days and thereafter refed. Serum concentrations of nonesterified fatty acids and beta-hydroxybutyric acid were initially increased by the nonfeeding, and followed by decreases in concentrations of cholesteryl esters, phospholipids, apolipoprotein (apo) B-100 and apoA-I. The apoC-III concentration was not distinctly decreased. Haptoglobin and serum amyloid A were induced during the nonfeeding and refeeding process. Haptoglobin was distributed in different proportions in the high-density lipoprotein, very high-density lipoprotein and the lipoprotein-deficient fractions, whereas almost all serum amyloid A was associated with the high-density lipoprotein fraction. These results suggest that the decreases in lipoprotein concentrations and induction of acute-phase proteins found in cows with fatty liver and those with fatty liver-related diseases such as ketosis are primarily due to the reduced feed intake near parturition.     

Decreased serum apolipoprotein A-I concentrations in cows infected with Salmonella typhimurium.

Serum apolipoprotein A-I concentrations in cows infected with Salmonella Typhimurium were evaluated to assess its relevance in salmonellosis. Apolipoprotein A-I has been shown in rats to be secreted by the intestine as well as the liver. Clinical symptoms such as diarrhea revealed an outbreak of salmonellosis in 22 cows on a farm, and sera were obtained at 6 (acute phase), 16, 28 (convalescent period) and 42 d (postconvalescent period) after the outbreak. Apolipoprotein A-I concentrations (mean +/- SD, mg/mL), determined by ELISA, were 0.598 +/- 0.497 (day 6), 0.111 +/- 0.060 (day 16), 0.432 +/- 0.311 (day 28) and 0.727 +/- 0.516 (day 42). Compared with the concentration at day 42, those at 16 and 28 d were significantly (P < 0.01, P < 0.05) lower, but that at day 6 was not. The serum concentration of apolipoprotein B-100 (of liver origin in cattle) was unaltered during the course of salmonellosis. The concentration of apolipoprotein A-I was positively correlated with those of serum total cholesterol (r = 0.589, P < 0.01) and phospholipids (r = 0.590, P < 0.01). These results suggest that apolipoprotein A-I in cattle is in part of intestinal origin, and also that its decreased serum concentration in salmonellosis can be attributed to the reduced intestinal synthesis or secretion of this apolipoprotein. Moreover, as a potential carrier for dietary lipids such as cholesterol, determination of serum apolipoprotein A-I concentration is suggested to be useful when assessing the nutritional status of the affected cows.     

Macromineral status of dairy cows with concurrent left abomasal displacement and fatty liver

Abstract

AIM: To evaluate the macromineral status of field cases of dairy cows surgically treated for left abomasal displacement (LDA), with concurrent fatty liver of different severity, and compare this for animals that died or recovered.

METHODS: Sixty-eight Holstein dairy cows with LDA and 110 control cows, from 28 farms, were used in the study. Blood samples and liver biopsies were obtained during standing surgery for correction of LDA, and from control cows. The concentration of macrominerals in serum, and of total lipids (tLPD) and triglycerides (TG) in liver were determined. Liver was examined histologically, and classified for its severity of fatty liver. Cows with LDA were grouped according to severity of fatty liver. Cows in Groups 1 to 3 recovered, whereas those in Group 4 died within 4 weeks of surgery. Group 1=mild (n=4) or moderate (n=6 cows, n=4 heifers) fatty liver, Group 2 = moderate to severe fatty liver (n=13), Group 3=severe fatty liver (n=15 cows, n=5 heifers), Group 4 = severe fatty liver (n=17 cows, n=4 heifers).

RESULTS: The concentration of macrominerals in serum was affected by the concurrence of fatty liver and LDA; Ca, K and Mg were significantly (p<0.05) lower in animals that died than those that survived. For cows with severe fatty liver, concentrations of tLD and TG were higher in the animals that died compared with those that recovered (p<0.01). Cows with LDA and severe fatty liver that died were earlier in lactation (median days in milk (DIM) 13 days) compared with the other cows with LDA (median DIM 21–26 days) (p<0.05); they were also significantly older (median 6 years old) than cows in the other groups (median 4 or 5 years old) (p–0.05).

CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of macrominerals in serum were influenced by the concurrence of LDA and fatty liver. Animals with low concentrations of Ca, K and Mg had a guarded prognosis. The concentration of K should always be evaluated in cows with LDA and concurrent fatty liver when providing a prognosis. Most cows with severe fatty liver were detected in the first 4 weeks of lactation, but older animals and those that had more recently calved had a worse prognosis.     

Utilization of intestinal triglyceride-rich lipoproteins in mammary gland of cows

Elution profiles of total lipoproteins, apolipoprotein B (apoB) concentrations in lipoproteins, and plasma triglyceride (TG) levels were examined in early-, late-, and non-lactating cows. Additionally, arteriovenous (A-V) differences were also measured to elucidate the uptake of TG and apoB-containing lipoproteins in mammary gland. Non-lactating cows showed three major peaks corresponding to triglyceride-rich lipoprotein (TRL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fraction, whereas both early- and late-lactating cows revealed two peaks corresponding to TRL and HDL. The peak area of TRL in early- and late-lactating cows were significantly (p < 0.05) smaller than that in non-lactating cows. The plasma TG levels and apoB-48 concentrations of TRL in early- and late-lactating cows were also significantly (p < 0.01) lower. Furthermore, early lactating cows showed significantly (p < 0.05) larger A-V differences in both plasma TG and apoB-48 concentration of TRL than those in late- and non-lactating cows. These results suggested that TG in exogenous (intestinal) TRL was utilized for milk fat synthesis in lactating mammary gland of cows by the receptor-mediated uptake.     

Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia.

The metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.     

Decreased Serum Lecithin:Cholesterol Acyltransferase Activity in Spontaneous Cases of Fatty Liver in Cows

Nakagawa, H., Oikawa, S., Oohashi, T. and Katoh, N., 1997. Decreased serum lecithin:cholesterol acyltransferase activity in spontaneous cases of fatty liver in cows. Veterinary Research Communications, 21 (1), 1-8. Lecithin:cholesterol acyltransferase (LCAT) activity in serum was evaluated in spontaneous cases of fatty liver in cows. The enzyme activity of 631 ± 62 U (mean ± SEM, decrease in nmol of free cholesterol per h per ml of serum) in cows with fatty liver (n = 16) was significantly (p < 0.01) lower than that in cows without fatty liver (979 ± 22 U; n = 16). In addition to the decrease in LCAT activity, the concentrations of phosphatidylcholine (a fatty aryl donor for esterification of free cholesterol) and of cholesteryl esters (products of the LCAT reaction) were reduced in the high-density lipoprotein fractions from cows with fatty livers. The concentration in the serum of apolipoprotein A-I, an activator of LCAT, was also reduced in cows with fatty livers. These results suggest that the decreased LCAT activity, which may be attributable to impaired hepatic secretion or to the suppression of the activity in the plasma by reduced concentrations of phosphatidylcholine and apolipoprotein A-I, resulted in the lower concentrations of cholesteryl esters. Because cholesteryl esters are utilized in steroidogenic tissues for the synthesis of steroid hormones such as progesterone and glucocorticoids, an insufficient supply of the cholesterols may be of relevance to the reduced fertility and immune competence observed in cows with fatty livers.     

Decreased concentration of serum apolipoprotein C-III in cows with fatty liver, ketosis, left displacement of the abomasum, milk fever and retained placenta

Apolipoprotein (apo) C-III is a low molecular mass protein mainly distributed in the high-density lipoprotein (HDL) fraction. In cows with postparturient diseases such as ketosis, concentrations of cholesterol, phospholipids and apoA-I and the activity of lecithin:cholesterol acyltransferase, which are mainly distributed in or functionally associated with HDL, are reduced. The purpose of the present study was to examine whether the serum concentration of apoC-III was similarly decreased in the postparturient diseases. Compared with healthy controls, the apoC-III concentration was significantly (P<0.01) decreased in cows with fatty liver, ketosis, left displacement of the abomasum, milk fever and retained placenta. Concentrations of apoC-III in the HDL fractions from diseased cows were also lower than in controls. Of the diseased cows, the decreased apoC-III concentration was particularly distinct in cows with milk fever. Increased nonesterified fatty acid and reduced free cholesterol, cholesteryl ester and phospholipid concentrations were observed in cows with milk fever, as in the other diseased cows. The decrease in the apoC-III concentration is suggested to be closely associated with the postparturient disorders, in particular with milk fever.     

The activity of lecithin: Cholesterol acyltransferase in the serum of cows at parturition or with fatty liver

The activity of lecithin: cholesterol acyltransferase (LCAT), which is responsible for esterification of plasma cholesterol, was evaluated in bovine serum. It was associated with the high-density lipoprotein fraction that contains apolipoprotein A–I, an activator of LCAT. In lactating cows, the activity was around 1000 U (decrease in nmol of free cholesterol per h per ml of serum), slightly higher than in 1-month-old calves. LCAT activity decreased around parturition, at which the time the serum concentrations of cholesteryl esters and free cholesterol were concomitantly decreased. A reduced LCAT activity was also found in cows with fatty livers induced by the administration of ethionine. In the cows with fatty livers, the serum concentration of cholesteryl esters was markedly decreased, whereas that of free cholesterol was only slightly decreased, thereby increasing the free- to esterified-cholesterol ratio. These results suggest that the decrease in LCAT activity may be involved in the reduction in fertility associated with fatty liver because esterification of cholesterol by LCAT is essential for its transport from the liver to peripheral tissues, such as the corpus luteum, and because cholesterol serves as the source of progesterone synthesis in the latter organ.Abbreviations apoA–I apolipoprotein A–I - CE cholesteryl esters - CM chylomicron - FC free cholesterol - HDL high-density lipoprotein - IDL intermediate-density lipoprotein - LCAT lecithin:cholesterol acyltransferase - LDL low-density lipoprotein - VHDL very high-density lipoprotein - VLDL very low-density lipoprotein     

Reduced concentrations of apolipoproteins B-100 and A-I in serum from cows with retained placenta.

The purpose of the present study was to evaluate apolipoprotein B-100 and A-I concentrations in cows with retained placenta. Animals used were cows with retained placenta alone (n = 10), those with both retained placenta and ketosis (n = 7), and controls (n = 10). Apolipoprotein B-100 concentrations at 2 to 4 d after parturition were significantly (P < 0.01) decreased in cows with retained placenta alone (mean +/- SD, 0.084 +/- 0.029 mg/ML of serum) when compared with those in control cows (0.154 +/- 0.022 mg/mL). Apolipoprotein A-I concentrations (0.713 +/- 0.177 mg/ML) were also significantly (P < 0.05) lower than those of controls (0.895 +/- 0.159 mg/mL). These decreases were more distinct for apolipoproteins B-100 (55% of controls) than A-I concentrations (80% of controls). Concentrations of apolipoprotein B-100 (0.071 +/- 0.032 mg/mL; P < 0.01) and A-I (0.708 +/- 0.189 mg/mL; P < 0.05) in the cows with both retained placenta and ketosis were also reduced, when compared with values in controls. Other than apolipoproteins, cows with retained placenta alone had significantly (P < 0.01) higher serum nonesterified fatty acids, and lower triglyceride concentrations. Significantly (P < 0.01) higher nonesterified fatty acids and lower triglyceride concentrations were similarly observed in cows with both retained placenta and ketosis.     

Relevance of apolipoproteins in the development of fatty liver and fatty liver-related peripartum diseases in dairy cows

Most metabolic diseases in dairy cows occur during the peripartum period and are suggested to be derived from fatty liver initially developed during the nonlactating stage. Fatty liver is induced by hepatic uptake of nonesterified fatty acids that are released in excess by adipose tissues attributable to negative energy balance. The fatty accumulation leads to impairment of lipoprotein metabolism in the liver, and the impairment in turn influences other metabolic pathways in extrahepatic tissues such as the steroid hormone production by the corpus luteum. Detailed understanding of the impaired lipoprotein metabolism is crucial for elucidation of the mechanistic bases of the development of fatty liver and fatty liver-related peripartum diseases. This review summarizes results on evaluation of lipoprotein lipid and protein concentrations and enzyme activity in cows with fatty liver and those with ketosis, left displacement of the abomasum, milk fever, downer syndrome and retained placenta. Obtained data strongly suggest that decreases in serum concentrations of apolipoprotein B-100, apolipoprotein A-I and apolipoprotein C-III, a reduction in activity of lecithin:cholesterol acyltransferase and induction of haptoglobin and serum amyloid A are intimately related to the development of fatty liver and fatty liver-related diseases. Moreover, determination of the apolipoprotein concentrations and enzyme activity during the peripartum period is useful for early diagnoses of these diseases.     

肝脏极低密度脂蛋白合成和分泌的研究进展

肝脏中极低密度脂蛋白(very low-density lipoprotein,VLDL)的过量沉积是引起脂质代谢紊乱进而形成脂肪肝的主要原因.本文综述了VLDL组装过程的最新特点以及肝脏中VLDL合成和分泌的影响因素,包括与VLDL合成相关的载脂蛋白B- 100( apoB-100)的结构和功能、微粒体甘油三酯转运蛋...     

Changes of serum 3-methylhistidine concentration and energy-associated metabolites in dairy cows with ketosis

The present study examined the Serum 3-methylhistidine concentrations and energy-associated variables of 5 healthy Holstein cows and 5 Holstein cows with ketosis. The serum total cholesterol and apolipoprotein B-100 concentrations and lecithin-cholesterol acyltransferase (LCAT) activity of the ketotic cows were lower than those of the healthy cows 14 days before parturition. The serum non-esterified fatty acid (NEFA) concentration on the day of parturition and 3-methylhistidine concentration 14 days after parturition were higher in the ketotic cows. The serum 3-methylhistidine concentration 14 days after parturition was negatively correlated with the serum LCAT activity 14 days before parturition and was positively correlated with the serum NEFA concentration on the day of parturition. Insufficiency of cholesterol metabolism and acceleration of body fat degradation occur before parturition in cows with ketosis, and these characteristics are correlated with acceleration of protein degradation after parturition.     

Efficacy of sodium borate in the prevention of fatty liver in dairy cows

The effects of sodium borate (100 mg/kg body weight, p.o., 15 days) from a month before expected calving until a month after calving were evaluated in dairy cows susceptible to fatty liver. Cows received either sodium borate (n = 13) or no treatment (n = 10). All cows had mild fatty livers and increased plasma triglycerides and very low density lipoprotein (VLDL) concentrations at the beginning of the experiment. The control group of cows developed significant fatty liver after calving, and 2 of them had severe fatty liver associated with clinical and biochemical abnormalities. There were no clinicopathological signs related to sodium borate administration. Serum triglycerides and VLDL concentrations before calving decreased significantly at calving and after calving in controls, and they were within the normal range only after calving. There were significant alterations during the experiment in some hematological and chemical variables between groups, within period, but they were within the normal range. Unlike treated cows, serum triglycerides and VLDL concentrations correlated with liver fat content after calving in untreated cows. Our results document that sodium borate decreases the degree of fatty liver in dairy cows during early lactation.     

Induction of fatty liver in cows by ethionine administration and concomitant decreases of serum apolipoproteins B-100 and A-I concentrations.

Ethionine, an analogue of methionine, induces fatty liver in rats by inhibiting protein synthesis, including that of apolipoproteins in liver. Ethionine was administered to cows to elucidate the participation in fatty liver development of impaired triglyceride secretion from liver attributable to decreased apolipoprotein synthesis. The administration resulted in a significant increase of liver triglyceride contents. Several apolipoproteins were found to have decreased concentrations. In particular, apolipoprotein B-100 in very low-density (0.95 to 1.006 g/ml) lipoprotein and in low-density (1.006 to 1.063 g/ml) lipoprotein fractions was greatly reduced. The decreases of apolipoprotein B-100 concentrations in the 2 lipoprotein fractions were at least partly correlated to the decreased triglyceride concentrations in the respective fractions. Decreased concentrations of apolipoprotein A-I in high-density (1.063 to 1.210 g/ml) lipoprotein were also observed, although not as distinctly as with apolipoprotein B-100. Total cholesterol and phospholipid concentrations in low- and high-density lipoprotein fractions were decreased. The decrease in cholesterol was attributed to reduced concentrations of cholesteryl esters. It was suggested that the impaired lipid secretion from liver attributable to the decreased apolipoprotein concentrations has a role in ethionine-induced fatty liver of cows.     

Fatty acid profiles in relation to triglyceride level in the liver of dairy cows

To elucidate possible relationships between triglyceride (TG) levels and fatty acid composition in bovine liver, hepatic TG and seven individual fatty acids were measured in 23 Holstein dairy cows, of them 6 are healthy. Liver TG level was greater than 3 % in 12 cows which were ruled fatty liver. Palmitic and oleic acid proportions were significantly higher in fatty liver cows than in the healthy cows, while stearic acid was lower in fatty liver cows. With increased liver TG, stearic acid proportions decreased dramatically. Results indicate that hepatic lipidosis markedly alters the proportions of the various fatty acids in the liver of dairy cows.     

Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis

This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P < 0.01). In the liver, the hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.     

Relationship between serum TNF activity and insulin resistance in dairy cows affected with naturally occurring fatty liver

To clarity the relationship between tumor necrosis factor (TNF) and insulin resistance in dairy cows affected with fatty liver, naturally occurring cases were investigated. The affected cows were classified into following three groups according to histopathologic findings of the liver: mild fat droplet deposition (group 1; n=11), severe fat droplet deposition (group 2; n=10), and cloudy swelling (group 3; n=8). Serum TNF activities in Group 2 (8.67 +/- 2.16 U/ml) and Group 3 (11.65 +/- 1.92 U/ml) were significantly higher than that in Group 1 (3.57 +/- 0.81 U/ml) (p<0.05). The insulin-tolerance tests showed that the insulin-stimulated glucose disposal rates (GDR) in Group 2 (27.6 +/- 7.8%) and Group 3 (15.8 +/- 9.1%) were significantly lower than that in Group 1 (41.7 +/- 9.8%). There was a significant negative correlation between serum TNF activity and GDR in affected cows (r=-0.56, p<0.01). These results indicate that serum TNF activity is correlated with insulin resistance in cows with fatty liver.