Ketone Body Concentrations Research Articles

Effect of Medium-Chain Triglycerides on Postprandial Concentrations of Remnant-Like Particles in Healthy Men.

A high concentration of remnant-like particles (RLP) has shown to be an arteriosclerosis risk factor that strongly reflects disorders of chylomicron and VLDL metabolism in patients with hyperlipidemia. The purpose of this study was to determine the serum concentrations of RLP-cholesterol after intake of meals containing medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) in 29 healthy men. Test meals were prepared by a nationally registered dietitian as a pilaf containing 10 g of MCT or LCT and commercial clear soup. Blood samples were collected at 0, 2, 3, 4, 6 and 8 h after intake of the test meals. The concentrations of serum triglyceride, chylomicrons, chylomicron-triglyceride, RLP-cholesterol, VLDL-cholesterol, and VLDL-triglyceride after intake of MCT were lower than those after intake of the same amount of LCT. Moreover, the areas under the time-concentration curves of triglyceride, chylomicrons and RLP-cholesterol after intake of MCT were significantly lower than those after intake of LCT. The increases in concentrations of serum insulin and total ketone bodies after intake of MCT were significantly greater than those after intake of LCT. These results suggest that MCT may reduce the risk of coronary arteriosclerotic disease by attenuating the postprandial increase of RLP that is closely correlated with arteriosclerosis.

Intracranial administration of transforming growth factor-beta3 increases fat oxidation in rats.

The effects of intracranial transforming growth factor (TGF)-beta3 on spontaneous motor activity and energy metabolism were examined in rats. After injection of TGF-beta3 into the cisterna magna of the rat, spontaneous motor activity decreased significantly for 1 h. The intracranial injection of TGF-beta3 produced an immediate decrease in respiratory exchange ratio (RER). No significant changes were observed in energy expenditure. TGF-beta3 induced a significant increase in total fat oxidation and a decrease in total carbohydrate oxidation. Furthermore, the serum substrates associated with fat metabolism were significantly altered in rats injected with TGF-beta3. Both lipoprotein lipase activity in skeletal muscle and the concentration of serum ketone bodies increased, suggesting that the increase in fat oxidation caused by TGF-beta3 may have occurred in the liver and muscle. Intracranial injection of TGF-beta3 appeared to evoke a switch in the energy substrates accessed in energy expenditure. These results suggest that the release of TGF-beta3 in the brain by exercise is a signal for regulating energy consumption.

Fuel use and metabolic response to endurance exercise: a wind tunnel study of a long-distance migrant shorebird

This study examines fuel use and metabolism in a group of long-distance migrating birds, red knots Calidris canutus (Scolopacidae), flying under controlled conditions in a wind tunnel for up to 10 h. Data are compared with values for resting birds fasting for the same time. Plasma levels of free fatty acids, glycerol and uric acid were elevated during flight, irrespective of flight duration (1-10 h). Triglyceride levels, the estimated concentration of very-low-density lipoproteins (VLDLs) and beta-hydroxybutyrate levels were lower during flight, while glucose levels did not change. In flying birds, plasma levels of uric acid and lipid catabolites were positively correlated with the residual variation in body mass loss, and lipid catabolites with energy expenditure (as measured using the doubly labelled water method), after removing the effect of initial body mass. The plasma metabolite levels indicate: (i) that the rates of catabolism of lipids from adipose tissue and of protein are higher during flight; (ii) that low ketone body concentrations probably facilitate fatty acid release from adipose tissue; (iii) that low triglyceride and VLDL levels do not indicate the use of an additional pathway of fatty acid delivery, as found in small birds; and (iv) that the relationships between energy expenditure, body mass loss and metabolic pattern suggest that a higher individual energy expenditure entails a higher rate of catabolism of both lipids and protein and not a shift in fuel substrate.

Relationship between concentration of citrate and ketone bodies in cow's milk.

The authors' hypothesis is that the members of the tricarboxylic acid cycle (TCA cycle) such as citrate decrease in association with increased ketone body formation. To prove this hypothesis the connection between ketone bodies and citrate formation of milk was studied. A fluorimetric method was used to determine citrate and a headspace sampling gas chromatographic (GC) method was developed for determination of ketone bodies. Under real conditions of milk sampling, transport and storage, preserved milk samples of 119 clinically healthy dairy cows obtained in the 48 hours after milking were investigated. A low level of acetoacetate (ACAC) was found in all samples. This fact can be explained by the spontaneous decarboxylation of acetoacetate during sample storage (previously decarboxylised acetoacetate = pdACAC) and, consequently, the majority of the amount of acetoacetate in the samples (AC + pdACAC) appeared in the measured acetone concentrations. Based on the measured acetone concentration of milk samples two groups were formed retrospectively: HA (high-acetone) group (n = 41) with an AC + pdACAC concentration of > 0.4 mmol/l and a LA (low-acetone) group (n = 78) with an AC + pdACAC level of < or = 0.4 mmol/l. In the milk of cows of Group HA a positive correlation (r = +0.623) and linear connection between acetone (AC + pdACAC) and beta-hydroxybutyrate (BOHB) levels was found [BOHB = 2.491 + 0.586 x (pdAC + ACAC)]. Furthermore, in this group a negative correlation between citrate and BOHB and AC + pdACAC was also established (r = -0.579). Focusing on the results of this group the authors found a significant drop of AC + pdACAC and citrate during the metabolically critical first 1-4 weeks of lactation. For this reason they suggest that simple, easy, automated methods (i.e. flow injection analysis, Fourier transformation infrared analysis) should be introduced for the simultaneous determination of acetone and citrate concentration in milk to make the evaluation of the energy status of high-producing dairy cows easier and more certain.

Effects of a progesterone-induced protein with a molecular weight of 20 kDa (PIP-20) on carbohydrate metabolism and growth of Day 8 equine embryos in culture

During the past 50 years, the fertility of high-producing lactating dairy cows has decreased, associated with intensive selection for increased milk production. The physiological and metabolic changes associated with high milk production, including decreased (glucose, insulin, IGF-I) or increased (nonesterified fatty acids, ketone bodies) concentrations of circulating metabolites during nutrient partitioning associated with negative energy balance as well as uterine and nonuterine diseases have been linked with poor reproductive efficiency. Fertilization is typically above 80% and does not seem to be the principal factor responsible for the low fertility in dairy cows. However, early embryonic development is compromised in high-producing dairy cows, as observed by most embryonic losses occurring during the first 2 weeks after fertilization and may be linked to compromised oocyte quality due to a poor follicular microenvironment, suboptimal reproductive tract environment for the embryo, and/or inadequate maternal–embryonic communication. These and other factors related to embryo development will be discussed.

Hormone-sensitive Lipase Deficiency in Mice Changes the Plasma Lipid Profile by Affecting the Tissue-specific Expression Pattern of Lipoprotein Lipase in Adipose Tissue and Muscle

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.

Purification, Characterization, and Biological Activity of Insulins from the Spotted Dogfish, Scyliorhinus canicula, and the Hammerhead Shark, Sphyrna lewini

Insulin was purified from pancreatic extracts of two elasmobranch species belonging to different families in the order Carcharhiniformes, the European spotted dogfish, Scyliorhinus canicula (Scyliorhinidae), and the hammerhead shark, Sphyrna lewini (Carcharhinidae). The amino acid sequence of dogfish insulin was established as A-chain GIVDHCCRNT10CSLYDLEGYC20NQ and B-chain LPSQHLCGSH10LVETLYFVCG20QKGFYYVPKV30. The primary structure of hammerhead shark insulin was similar to that of dogfish insulin with only 2 amino acid substitutions at A8 (R → H) and B30 (V → I). The elasmobranch insulins were markedly different from human insulin (17 amino acid substitutions) but all the residues in human insulin that are believed to be important in determining the receptor binding conformation (B6, B8, B11, B13, B23, B24, B25, A2, A3, and A19) have been conserved in the elasmobranch insulins with the exception of the conservative substitution Phe → Tyr at B25. Consistent with this, dogfish and human insulin showed almost identical binding affinity to the recombinant solubilized human insulin receptor (KD values of 14.0 and 18.6 pM, respectively; relative potency 133%). Previous studies have shown that bovine insulin produces severe and sustained hypoglycemia in elasmobranchs but the effect is of slow onset. Bolus arterial injections of dogfish insulin (10 nmol·kg−1) into unanesthetized, fasting dogfish (n = 9) produced no changes in blood glucose, 3-hydroxybutyrate, and acetoacetate concentrations over a 4-h period. In a second series of experiments (n = 7), dogfish insulin (10 nmol·kg−1) produced a significant (P < 0.05) fall in blood glucose after 12 h that persisted for at least 48 h, but no change in ketone body concentrations. The data indicate that the metabolic actions of an endogenous elasmobranch insulin in an elasmobranch are similar to those previously described for mammalian insulin.

Nutritional factors that affect the postnatal metabolic adaptation of full-term small- and large-for-gestational-age infants.

To document metabolic adaptation to ex utero life in small- (SGA) and large-for-gestational-age (LGA) infants in relation to fetal nutrition and postnatal feeding practices. In a prospective study, 65 SGA (< or = second centile) and 39 LGA (> or = 98th centile) full-term infants were recruited. Anthropometry was performed within the first 48 hours. There was full support of breastfeeding and close clinical observation. Blood glucose and ketone body (kb) concentrations were measured prefeed for the first 7 postnatal days. Infants were exclusively breastfed (BF), breastfed with formula milk supplementation (FS), or exclusively formula milk fed (FF). Within the SGA group, a measure of "thinness," the midarm circumference/head circumference ratio, was significantly correlated to the number of episodes of blood glucose < 2.00 mmol/L. Epoch (age at sampling) analysis in this group showed no difference in blood glucose levels across the different feeding groups but revealed a statistically significant greater kb concentration for infants who were exclusively breastfed. For SGA infants, the median peak kb concentration (peak kb) was significantly different for BF, FS, and FF groups. Multiple regression analysis for the SGA group demonstrated that peak kb concentration was negatively related to the volume of formula milk, independent of blood glucose levels and neonatal anthropometry. For LGA infants, low blood glucose levels were offset by kb concentrations equivalent to those observed in infants who were appropriate for gestational age. Neonatal ability to generate kb when blood glucose values are low depends more on successful breastfeeding than on size for gestational age or neonatal nutritional status. Routine blood glucose monitoring of LGA infants with no additional risk factors is not necessary. Routine formula milk supplementation for LGA and SGA infants should not be recommended.

Phosphoenolpyruvate carboxykinase revisited: Insights into its metabolic role

Phosphoenolpyruvate carboxykinase revisited: Insights into its metabolic role

Metabolic Effects of Chromium Supplementation in Dairy Cows in the Peripartal Period

Pechova A., A. Podhorsk˘, E. Lokajova, L. Pavlata, J. Illek: Metabolic Effects of Chromium Supplementation in Dairy Cows in the Peripartal Period. Acta Vet. Brno 2002, 71: 9-18. The aim of the work was to assess the effects of supplemental chromium (Cr) on metabolism of dairy cows in the peripartal period. Rations fed to dairy cows in a herd of Holstein cattle with mean milk yield of 7 500 l were supplemented with chromium-enriched yeast (Co-Factor III Chromium Yeast, Alltech, 0.1% Cr3+) at 10 mg of Cr per animal per day. The treatment was started 21 days before the expected delivery date and discontinued 30 days after the delivery. Blood and urine samples were collected from ten experimental and ten control cows at weekly intervals, the state of health was monitored by regular clinical examinations, and milk yield for the first 100 days of lactation was recorded. The results indicate favourable effects of the supplementation on energy metabolism. The Cr-supplemented cows showed significantly higher blood glucose concentrations at post-partum (p.p.) weeks 4 (4.25 ± 0.21 vs. 3.74 ± 0.36 mmol·l-1; p < 0.01) and 5 (4.06 ± 0.41 vs. 3.64 0.28 mmol·l-1; p < 0.05) and lower ketone bodies concentration at p.p. week 4 (0.88 ± 0.11 vs. 1.38 ± 0.66 mmol·l -1 ; p < 0.05). The Cr-supplemented cows showed also significantly lower bilirubin concentration at p.p. week 2 (3.93 ± 0.84 vs. 6.47 ± 3.25 µmol·l -1 ; p < 0.05) and lower catalytic activities of aspartate aminotransferase at p.p. weeks 3 (1.37 ± 0.14 vs. 1.66 ± 0.20 µkat·l -1 ; p < 0.01) and 5 (1.16 ± 0.08 vs. 1.47 ± 0.18 µkat·l -1 ; p < 0.01) and lactate dehydrogenase at p.p. week 5 (27.35 ± 3.76 vs. 33.61 ± 5.61 µkat·l -1 ; p < 0.05). No effects on the metabolism of nitrogen substances or minerals, insulin concentration in blood serum, and blood Cr concentration were observed. Chromium excretion in urine increased after parturition; higher concentrations were found in Cr-supplemented cows at p.p. weeks 3 (7.14 ± 1.72 vs. 5.00 ± 1.26 µg·l-1; p < 0.01) and 4 (8.40 ± 3.13 vs. 4.04 ± 1.32 µg·l-1; p < 0.01). Although chromium supplementation in the peripartal period significantly improved variables characterising the energy metabolism, no effects on milk yield for the first 100 days of lactation or on the incidence of clinical diseases were demonstrable.

Chronic exposure to beta-hydroxybutyrate impairs insulin action in primary cultures of adult cardiomyocytes.

Type 1 and type 2 diabetic patients often show elevated plasma ketone body concentrations. Because ketone bodies compete with other energetic substrates and reduce their utilization, they could participate in the development of insulin resistance in the heart. We have examined the effect of elevated levels of ketone bodies on insulin action in primary cultures of adult cardiomyocytes. Cardiomyocytes were cultured with the ketone body beta-hydroxybutyrate (beta-OHB) for 4 or 16 h, and insulin-stimulated glucose uptake was evaluated. Although short-term exposure to ketone bodies was not associated with any change in insulin action, our data demonstrated that preincubation with beta-OHB for 16 h markedly reduced insulin-stimulated glucose uptake in cardiomyocytes. This effect is concentration dependent and persists for at least 6 h after the removal of beta-OHB from the media. Ketone bodies also decreased the stimulatory effect of phorbol 12-myristate 13-acetate and pervanadate on glucose uptake. This diminution could not be explained by a change in either GLUT-1 or GLUT-4 protein content in cardiomyocytes. Chronic exposure to beta-OHB was associated with impaired protein kinase B activation in response to insulin and pervanadate. These results indicate that prolonged exposure to ketone bodies altered insulin action in cardiomyocytes and suggest that this substrate could play a role in the development of insulin resistance in the heart.

Acute effects of growth hormone on metabolism of pancreatic hormones, glucose and ketone bodies

Controversy exists as to whether acute administration of growth hormone has insulin-like effects. In conscious dogs, acute effects on plasma flows, plasma glucose, hepatic glucose output, free fatty acids, ketone bodies, insulin, and glucagon were determined following intravenous injection of 1 mg of growth hormone extracted from the canine pituitary gland. The following results were obtained: (1) Plasma flows in the portal vein, hepatic artery and hepatic vein were significantly increased 20 min after growth hormone administration. (2) By 40 min after growth hormone, the glucose concentration in these three vessels was significantly increased. (3) Hepatic glucose output was significantly increased 60 min after growth hormone administration. (4) Free fatty acids levels were significantly but transiently increased at 20 min, while ketone body concentrations were elevated at 120–180 min. (5) The insulin levels in the three vessels demonstrated a biphasic response. In the portal vein, they were significantly higher 20 min after growth hormone and again at 150–180 min. Glucagon concentrations were increased in all three vessels by 20 min and remained elevated for the remainder of the experiment. These results do not support an acute insulin-like action of growth hormone in normal dogs.

Ketone Bodies in Milk and Blood of Dairy Cows: Relationship between Concentrations and Utilization for Detection of Subclinical Ketosis

The objective of this study was to investigate the relationship between the concentrations of the different ketone bodies in milk and blood and to evaluate these concentrations for the detection of subclinical ketosis. A total of 60 multiparous cows were used. Concentrations of acetone, acetoacetate, and β-hydroxybutyrate were analyzed quantitatively in blood and milk, and the Ketolac strip test was used for semiquantitative determination of β-hydroxybutyrate in milk. Cows were defined subclinically ketotic when their concentration of blood β-hydroxybutyrate was over 1200 μmol/L. High correlation coefficients were observed between blood acetone and blood acetoacetate, and between blood and milk acetone. On the contrary, concentrations of milk and blood β-hydroxybutyrate were poorly correlated with the other concentrations of ketone bodies. The Ketolac strip test overestimated the concentrations of β-hydroxybutyrate in milk. For the detection of subclinical ketosis, the best sensitivity-specificity combination was obtained with the determination of acetoacetate in blood or milk, with threshold concentrations of 125 and 50 μmol/L, respectively. Determination of β-hydroxybutyrate in the milk via an enzymatic analysis or via the Ketolac strip test provided valuable results, with threshold concentrations of 70 and 100 μmol/L, respectively. The simplicity of use of the Ketolac strip test makes it a valuable way toinvestigate subclinical ketosis.

Ketosis and the generation of oxygen radicals in diabetes mellitus.

The long-term complications of diabetes remain a major public health issue. Over the last decade, many of the biochemical pathways by which hyperglycemia may cause cellular damage have been studied. These include increased polyol pathway and associated changes in intracellular redox state, increased diacylglycerol synthesis with consequent activation of specific protein kinase C isoforms, increased nonenzymatic glycation of both intra-and extracellular proteins, and increased oxidative stress (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11). Tissue injury then results from acute changes in protein function and chronic changes in protein expression. However, the molecular pathophysiology of altered membrane function and gene expression leading to tissue injury is still unclear. Type 1 diabetics frequently experience ketosis (hyperketonemia) because, in a state of insulin deficiency, body fuel is derived mainly from fat (12). The blood concentration of ketone bodies may reach 10 mM in diabetics with severe ketosis, compared with concentrations of less than 0.5 mM in normal individuals (12). It is known that ketosis can accelerate microangiopathy and underlying vascular disease and precipitate neuropathy in patients with long-duration diabetes (12). However, the underlying mechanisms by which ketosis promotes vascular disease in type 1 diabetic patients are unclear This chapter is focussed on the mechanisms that underlie the accelerated vascular disease and mortality in diabetic patients. To better differentiate among the complex interactions of various cell types, hormones and dynamic changes in the blood, we have used a cell culture model to accomplish the stated objectives. Specifically, this review discusses whether ketosis increases cellular oxidative stress/damage, and thereby promotes cell surface changes and adhesion between the monocytes and endothelial cells, a crucial step in the pathogenesis of vascular disease in diabetes.

Diabetes and life-styles: role of physical exercise for primary prevention.

Regular physical exercise has been known to be beneficial in the treatment of type 2 diabetes. Epidemiological studies of physical exercise: previous non-randomized studies suggested that a life-style intervention program involving diet and/or exercise reduced the progression of impaired glucose tolerance (IGT) to type 2 diabetes. Recent randomized controlled intervention trials also showed that diet and/or exercise intervention led to a significant decrease in the incidence of diabetes among those with IGT. Endocrinological and metabolic effects of exercise: in well controlled diabetic patients, physical exercise promotes utilization of blood glucose and lowers blood glucose levels. On the other hand, in poorly controlled diabetic patients with ketosis, physical exercise results in further rises in blood glucose, free fatty acids and ketone body concentrations. Long-term gentle regular jogging increases insulin action in respect of both carbohydrate and lipid metabolism despite no influence on body mass index or maximal oxygen uptake. A significant correlation was observed between deltaMCR (insulin sensitivity) and average daily steps Our recent data suggested that the improvement of insulin action by physical exercise was attributed, at least in part, to the increase in insulin-sensitive GLUT4 (glucose transporter 4) on the plasma membrane in skeletal muscle. In conclusion, as an adjunct to other forms of therapy, mild regular physical exercise will play an important role in primarily preventing type 2 diabetes.

Insulin sensitivity of glucose and fat metabolism in severe sepsis

In order to quantify the changes in insulin sensitivity, particularly of endogenous glucose production and fat metabolism, in patients with severe sepsis, a prospective study was conducted in five normal subjects and in five patients with severe sepsis hospitalized in an intensive care unit. The responses of endogenous glucose production, glucose utilization, plasma fatty acids and ketone body concentrations to progressive increase in plasma insulin levels (exogenous insulin infusion rates of 0, 0.5, 1 and 2 m-units x min(-1) x kg(-1)) were measured using the isoglycaemic clamp technique. Total glucose turnover was determined with D-[6,6-(2)H(2)]glucose. In each group, plasma glucose was maintained at basal levels (control subjects, 4.32+/-0.22 mmol x l(-1); patients with sepsis, 7.10+/-2.29 mmol x l(-1); P<0.05). Plasma insulin concentrations were comparable in the two groups at an insulin infusion rate of 0.4 m-unit x min(-1) x kg(-1) for controls and 0.5 m-unit x min(-1) x kg(-1) for patients with sepsis, but differed following infusion at 2 m-unit x min(-1) x kg(-1) (control subjects, 102+/-13.4 m-units x l(-1); patients with sepsis, 124.8+/-19.7 m-units x l(-1); P<0.05). Endogenous glucose production was completely suppressed in control subjects by the first insulin infusion (0.4 m-unit x min(-1) x kg(-1)), but was only suppressed during infusion at 1 m-unit x min(-1) x kg(-1) insulin in patients with sepsis. The glucose utilization rate increased significantly with exogenous insulin infusion in control subjects, but did not increase in patients with sepsis. Plasma non-esterified (free) fatty acid and ketone body levels were significantly decreased in both groups by the infusion of exogenous insulin, but the sensitivity of lipolysis was impaired in patients with sepsis. In conclusion, sepsis impaired to a varying extent the action of insulin on endogenous glucose production, glucose utilization, lipolysis and ketogenesis. Whole-body glucose uptake was the most affected, with a total lack of response to the elevated insulin levels obtained in this study. Suppression of endogenous glucose production and lipolysis could only be achieved with higher doses of insulin than those required in normal subjects.

First ovulation and ketone body status in the early postpartum period of dairy cows

The effect of ketone body status on occurrence of first ovulation during early lactation was assessed in 84 multiparous dairy cows under field conditions. Animals were equally distributed across 8 farms and were controlled by the same herd fertility monitoring program. Cows were visited twice antepartum and 6 times postpartum at weekly intervals between 5:30 and 8:30 AM. On these occasions, body condition scores and milk yields were measured, blood and milk samples were taken, cows were gynecologically examined, and parameters of reproduction were determined. The onset of first ovulation was specified by milk progesterone determination and rectal palpation. Cows starting postpartum ovarian cyclicity within or after 30 d were classified as early and late responders (ER and LR, respectively). Resumption of the estrous cycle within 30 d postpartum is considered optimal under practical conditions, and classification based on this threshold value resulted in groups of equal size and equal distribution of ER + LR cows within farms. Ketone bodies measured were βhydroxybutyrate in serum and acetoacetate and acetone in serum and milk. Blood serum and milk ketone body concentrations during the first 6 wk of lactation were higher in LR than in ER, whereas plasma glucose and nonesterified fatty acid and milk fat, protein and urea concentrations did not differ between groups. Maximal concentrations of ketone bodies from parturition to first ovulation were better predictors of the onset of the estrous cycle than mean or minimal concentrations over the same period. Milk acetone and serum β-hydroxybutyrate concentrations provided the most reliable information with regard to resumption of ovarian activity of all ketone bodies.

Effects of ketoacidosis on rat apolipoprotein A1 gene expression: a link with acidosis but not with ketones.

To determine if ketoacidosis contributes to reduced apolipoprotein A1 (apoA1) expression in insulin-deficient diabetic rats, we examined the regulation of apoA1 gene expression in response to changes in ambient pH or ketone body concentrations. Hepatic apoAI mRNA levels were reduced 42% in diabetic rats relative to nondiabetic controls (means+/-s.d.; 321.8+/-43.7 vs 438.7+/-58.8 arbitrary units; P<0.03). Neither endogenous apoA1 mRNA nor transcriptional activity of the rat apoA1 gene promoter (from -474 to -7) were altered by sodium butyrate or isobutyramide (0.3 mM to 10 mM) in Hep G2 or Caco-2 cells. Rat hepatic and intestinal apoA1 mRNA levels, and plasma apoA1 concentration, were not altered 24 h after isobutyramide administration (500 mg/kg by gavage). When the effect of altering ambient pH within a wide range commonly encountered in vivo was studied, acidosis (pH 6.7), relative to alkalosis (pH 7.9), decreased apoAI mRNA levels relative to glyceraldehyde-3-phosphate dehydrogenase mRNA by 47% in Hep G2 cells (P<0.025) and by 24% in Caco-2 cells (P<0.017). Acidosis did not alter cytomegalo virus (CMV)-beta-galactosidase activity, or the activity of the simian virus (SV40) early-region promoter, in either cell line transfected with the respective constructs. The lowering of ambient pH was associated with a graded reduction in apoAI promoter activity. At pH 6.7, apoAI promoter activity was reduced by 75% compared with promoter activity at pH 7.9. These observations indicate that acidosis, but not ketosis, contributes to the reduction in apoA1 expression during diabetic ketoacidosis by down-regulating apoAI promoter activity.

Hyperketonemia and the impairment of udder defense: a review.

The objective of this study was to review the possible relationships between hyperketonemia and the function of phagocytes with respect to the bovine udder defense mechanism. We hypothesize that an increased incidence of clinical mastitis in high-producing cows is caused by the impairment of the udder defense mechanism during hyperketonemia. First, we review the acute phase of udder defense mechanisms after intramammary infection. The physiological changes of cows in negative energy balance are subsequently discussed. Finally, possible relationships between udder defense and physiological changes during negative energy balance, especially hyperketonemia, are reviewed. The three stages of an acute phase of udder defense are: (1) immediately eliminating invading pathogens by phagocytes, (2) releasing inflammatory substances, especially chemoattractants, and (3) migration of polymorphonuclear leukocytes into the infected udder. Leukocytes from hyperketonemia subjects show a lower capacity of the phagocytic defense mechanism. In addition, the phagocytic and bactericidal capacities of neutrophils are reduced when these cells are acting in the presence of high concentrations of ketone bodies. Lower amounts of cytokine production after bacterial infection are observed in ketotic subjects. The chemotactic capacity of blood leukocytes is impaired in leukocytes obtained from ketotic cows. Lower numbers of blood leukocytes are observed in ketotic cows. In conclusion, the impairment of the udder defense mechanism in negative energy balance cows seems related to hyperketonemia.

Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis

Purpose: Diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) are two medical emergencies characterized by elevated total ketone body concentration. We aimed to determine differences in pathogenesis of ketoacidosis and its metabolic consequences by comparing both at presentation and during treatment, the different metabolic products and hormones involved in the ketoacidotic state. Materials and Methods: We studied 12 patients with DKA and 8 patients with AKA. On admission and every 4 hours for 24 hours during treatment, samples were drawn for determination of serum ketone bodies, lactate and pyruvate, insulin, and counterregulatory hormones (glucagon, cortisol, growth hormone, and catecholamines). Results: At presentation, with a similar β-hydroxybutyrate concentration, patients with DKA had a higher plasma glucose (32 mmol/L vs. 6.6 mmol/L), lower β-hydroxybutyrate/acetoacetate ratio (3:1 vs. 7:1), and a lower lactate/pyruvate ratio (11:1 vs. 19:1) than patients with AKA (all, P < .01). The mean time to resolve ketoacidosis in patients with AKA (6 ± 1 hour) was significantly shorter than in patients with DKA (16 ± 2 hours). At presentation, the mean insulin concentration in patients with DKA and AKA were similarly decreased (7.8 ± 2 and 10.3 ± 3 μU/mL, P = not significant [NS]).The mean glucagon level before therapy was 203 ± 15 pg/mL and 188 ± pg/mL for patients with DKA and AKA, respectively (P = NS). Levels of cortisol, growth hormone, and epinephrine at presentation and during the first 8 hours of treatment were higher in patients with DKA; however, the difference in these values did not reach statistical significance. During therapy, levels of counterregulatory hormones declined at similar rates and returned to normal values after resolution of ketoacidosis. Conclusions: Our results indicate that, in addition to a history of diabetes or alcoholism, patients with DKA and AKA differ in their metabolic parameters more than in their hormonal profile. The metabolic profile of DKA is characterized by a higher plasma glucose concentration, and lower β-hydroxybutyrate to acetoacetate and lactate to pyruvate ratios compared with patients with AKA. The initial hormonal profile in both ketoacidotic states is characterized by similarly decreased insulin levels and elevated levels of counterregulatory hormones. Copyright © 2000 by W.B. Saunders Company