Improved Energy Status Research Articles

The effect of aspartate on the energy metabolism in the liver of weanling pigs challenged with lipopolysaccharide.

This study was conducted to investigate whether aspartate (Asp) could improve liver energy status in the lipopolysaccharide (LPS)-challenged pigs. Twenty-four weaned pigs were assigned to four treatments: (1) nonchallenged control (control diet and saline-treated); (2) LPS-challenged control (the same control diet and LPS-challenged); (3) LPS + 0.5% Asp treatment (0.5% Asp diet and LPS-challenged); and (4) LPS + 1.0% Asp treatment (a 1.0% Asp diet and LPS-challenged). On d 19, the pigs were injected intraperitoneally with Escherichia coli LPS at 100 μg/kg body weight, and the same volume of 0.9% NaCl solution, respectively. All pigs were slaughtered at 24 h after LPS or saline injection, and the liver was collected for further analysis. Dietary supplementation with Asp improved liver energy status evidenced by the increased ATP concentration and adenylate energy charges, and the decreased AMP concentration and AMP/ATP ratio (p < 0.05). Asp supplementation increased the mRNA expression of key enzymes in hepatic glycolysis and tricarboxylic acid (TCA) cycle, including pyruvate kinase and citrate synthase (p < 0.05), and had a tendency to increase hepatic pyruvate dehydrogenase and isocitrate dehydrogenase β mRNA expression (p < 0.10). In addition, Asp increased the mRNA expressions of hepatic AMP-activated protein kinase (AMPK) α1, AMPKα2, silent information regulator (Sirt1), and proliferator-activated receptor-γ coactivator 1α (PGC1α) (p < 0.05). Moreover, Asp increased AMPKα phosphorylation (p < 0.05). These results indicated that dietary supplementation of Asp could improve energy status in LPS-injured liver, which might result from motivating the metabolism pathway of TCA cycle and glycolysis and stimulating the AMPK signaling pathway.

Prepartum and postpartum nutritional management to optimize fertility in high-yielding dairy cows in confined TMR systems

The 6 to 8-week period centered on parturition, known as the transition or periparturient period, is critical to welfare and profitability of individual cows. Fertility of high-producing cows is compromised by difficult transitions. Deficiencies in either nutritional or non-nutritional management increase risk for periparturient metabolic disorders and infectious diseases, which decrease subsequent fertility. A primary factor impeding fertility is the extent of negative energy balance (NEB) early postpartum, which may inhibit timing of first ovulation, return to cyclicity, and oocyte quality. In particular, pronounced NEB during the first 10 days to 2 weeks (the time of greatest occurrence of health problems) is critical for later reproductive efficiency. Avoiding over-conditioning and preventing cows from over-consuming energy relative to their requirements in late gestation result in higher dry matter intake (DMI) and less NEB after calving. A pooled statistical analysis of previous studies in our group showed that days to pregnancy are decreased (by 10 days) by controlling energy intake to near requirements of cows before calving compared with allowing cows to over-consume energy. To control energy intake, total mixed rations (TMR) must be well balanced for metabolizable protein, minerals and vitamins yet limit total DM consumed, and cows must uniformly consume the TMR without sorting. Dietary management to maintain blood calcium and rumen health around and after calving also are important. Opportunities may exist to further improve energy status in fresh cows. Recent research to manipulate the glucogenic to lipogenic balance and the essential fatty acid content of tissues are intriguing. High-producing cows that adapt successfully to lactation can have high reproductive efficiency, and nutritional management of the transition period both pre- and post-calving must facilitate that adaptation.

Once-daily milking during a feed deficit decreases milk production but improves energy status in early lactating grazing dairy cows

The objective of this study was to investigate the effect of milking frequency (MF) at 2 feeding levels (FL) on milk production, body condition score, and metabolic indicators of energy status in grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) grazed pasture and were milked twice daily (2×) from calving until 34±6d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2×2 factorial arrangement. Treatments consisted of 2FL: adequately fed [AF; 14.3kg dry matter intake (DMI)/cow per d] or underfed (UF; 8.3kg of DMI/cow per d) and 2 MF: 2× or once daily (1×). Treatments were imposed for 3wk. After the treatment period, all cows were offered a generous pasture allowance (grazing residuals >1,600kg of dry matter/ha) and milked 2×. During the 3-wk treatment period, we observed an interaction between FL and MF for energy-corrected milk (ECM), such that the decrease due to 1× milking was greater in AF than in UF cows (20 and 14% decrease, respectively). No interactions were found posttreatment. Cows previously UF produced 7% less ECM than AF cows during wk 4 to 12; however, no subsequent effect was observed of the previous underfeeding. Cows previously milked 1× produced 5% less ECM during wk 4 to 12, and differences remained during wk 13 to 23. During the 3-wk treatment period, UF cows lost 0.2 body condition score units (1–10 scale) and this was not affected by 1× milking. During the treatment period, UF cows had lower plasma glucose, insulin, and insulin-like growth factor I, and greater nonesterified fatty acids and β-hydroxybutyrate concentrations than AF cows. Cows milked 1× had greater plasma glucose, insulin, and insulin-like growth factor I, and lower nonesterified fatty acids and β-hydroxybutyrate concentrations compared with cows milked 2×. In conclusion, energy status was improved by 1× milking; however, when UF cows were milked 1×, milk production was reduced by more than underfeeding alone. The immediate and residual responses to 1× milking need to be considered when using this management strategy during a feed deficit.

Diet supplementation with clinoptilolite improves energy status, reproductive efficiency and increases milk yield in dairy heifers

The objective of this study was to investigate the effect of long-term dietary inclusion of clinoptilolite on the energy status, reproductive parameters and milk yield of dairy heifers. Eighty Holstein pregnant heifers were equally divided to two groups: treatment group heifers were fed the ration supplemented with 200 g clinoptilolite per day; control group heifers were fed the basal ration and served as controls. The experiment started on Day 210 of gestation and lasted until the end of the first lactation period. Blood samples were collected from each animal at the start of the experiment, 30 days later on the day of calving and then on a monthly basis and were analysed for serum glucose and ketone bodies. On the same days, all animals were monitored for body condition score. Cows were observed for heat every day and were inseminated at first heat after the 60th day postpartum. Calving to first heat interval, calving to first service interval, number of services per conception and calving interval were calculated for both groups. Milk yield for each cow was recorded monthly and 305-day milk yield was calculated. Clinoptilolite supplementation significantly increased body condition score and blood serum concentration of glucose and significantly decreased blood serum concentration of ketone bodies. Clinoptilolite also improved significantly the reproductive parameters evaluated and significantly increased milk production. These results indicate that daily dietary administration of 200 g of clinoptilolite can be used for the improvement of animal performance in dairy herds.

Effects of feeding fiber-fermenting bacteria to pigs on nutrient digestion, fecal output, and plasma energy metabolites1,2

Inclusion of feedstuffs with higher plant cell wall (fiber) content in swine diets has increased in recent years due to greater availability and lower cost, especially coproduct feeds, such as corn distillers dried grains with soluble (DDGS). Limitations of feeding higher fiber diets include increased fecal output, which can exceed manure storage volumes, and decreased energy density, which can decrease growth performance; dietary treatments that ameliorate these limitations would benefit pork producers. Grower pigs (n = 48; 61.1 kg initial BW) were used to establish the effects of supplementation of fiber-fermenting bacteria in a 2 × 4 factorial, consisting of 2 diets (standard and high fiber) and 4 bacterial treatments (A, no bacteria; and B, C, and D bacterial supplements). Increased fiber came from inclusion of soybean hulls (10%) and corn DDGS (20%) in the diet. The 3 bacterial supplements (all Bacteroides strains) were isolated from fecal enrichment cultures and selected for their fiber-fermenting capacity. The high fiber diet increased fecal output, blood cholesterol, and triglyceride concentrations, and digestibility of NDF, ADF, and S; CP digestibility decreased (P ≤ 0.10). The improved fiber digestibility and altered energy status of pigs fed the high fiber diet was primarily due to fermentation of soybean hulls, resulting in increased short-chain fatty acid production and absorption, and decreased dietary starch content. Overall, pigs fed the bacterial treatments had only increased blood cholesterol concentrations (P = 0.10). When individual bacterial treatments were compared, pigs fed Bacteria B had decreased fecal output (P ≤ 0.10) and both blood glucose and cholesterol concentrations were increased (P ≤ 0.10) compared with the other 3 treatments, indicating an improved energy status. Pigs fed Bacteria B increased both CP and ADF (P ≤ 0.10), and tended (P = 0.16) to have increased NDF digestibilities compared with pigs fed no bacteria (Treatment A), whereas pigs fed the other 2 bacterial treatments did not differ from pigs fed Bacteria B for nutrient digestibility. Both had similar fecal outputs to pigs fed no bacteria. This is the first report of reduction in fecal output and increased fiber digestibility with pigs fed live bacteria. Successful application of this bacterial treatment could result in improved pig performance and decreased manure volumes, both of which would improve profitability of producers.

LACTATION BIOLOGY SYMPOSIUM: Role of colostrum and colostrum components on glucose metabolism in neonatal calves1,2

In neonatal calves, nutrient intake shifts from continuous glucose supply via the placenta to discontinuous colostrum and milk intake with lactose and fat as main energy sources. Calves are often born hypoglycemic and have to establish endogenous glucose production (eGP) and gluconeogenesis, because lactose intake by colostrum and milk does not meet glucose demands. Besides establishing a passive immunity, colostrum intake stimulates maturation and function of the neonatal gastrointestinal tract (GIT). Nutrients and nonnutritive factors, such as hormones and growth factors, which are present in high amounts in colostrum of first milking after parturition, affect intestinal growth and function and enhance the absorptive capacity of the GIT. Likely as a consequence of that, colostrum feeding improves the glucose status in neonatal calves by increasing glucose absorption, which results in elevated postprandial plasma glucose concentrations. Hepatic glycogen concentrations rise much greater when colostrum instead of a milk-based colostrum replacer (formula with same nutrient composition as colostrum but almost no biologically active substances, such as hormones and growth factors) is fed. In contrast, first-pass glucose uptake in the splanchnic tissue tended to be greater in calves fed formula. The greater plasma glucose rise and improved energy status in neonatal calves after colostrum intake lead to greater insulin secretion and accelerated stimulation of anabolic processes indicated by enhanced maturation of the postnatal somatotropic axis in neonatal calves. Hormones involved in stimulation of eGP, such as glucagon and cortisol, depend on neonatal diet, but their effects on eGP stimulation seem to be impaired. Although colostrum feeding affects systemic insulin, IGF-I, and leptin concentrations, evidence for systemic action of colostral insulin, IGF-I, and leptin in neonatal calves is weak. Studies so far indicate no absorption of insulin, IGF-I, and leptin from colostrum in neonatal calves, unlike in rodents where systemic effects of colostral leptin are demonstrated. Therefore, glucose availability in neonatal calves is promoted by perinatal maturation of eGP and colostrum intake. There may be long-lasting effects of an improved colostrum supply and glucose status on postnatal growth and development, and colostrum supply may contribute to neonatal programming of performance (milk and growth) in later life, but data proving this concept are missing.

Caloric Restriction Enhances Cardiomyocyte Autophagy to Improve Energy Status and Ameliorates Left Ventricular Remodeling in the Postinfarction Heart

We previously reported that cardiomyocyte autophagy is an innate mechanism which prevents postinfarction cardiac remodeling. In this study, we examined effect of caloric restriction (CR), a potent inducer of autophagy, on postinfarction cardiac remodeling. Myocardial infarction (MI) was induced in mice. After one week of MI, mice were randomly divided into the following four groups. The control group was fed ad libitum (100%). Others were fed restricted diet respectively 80%, 60%, and 40% of the control mice's total calorie.

The effect of exercise on IL‐6‐induced cachexia in the ApcMin/+ mouse

BackgroundCachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL-6 accelerates cachexia in the ApcMin/+ mouse, but does not induce wasting in control C57BL/6 mice. With many chronic diseases, chronic inflammation and metabolic dysfunction can be improved with moderate exercise. A direct effect of regular moderate exercise on the prevention of IL-6-induced cachexia in the ApcMin/+ mouse has not been investigated. The purpose of this study was to assess the effects of exercise on the development of cachexia in the ApcMin/+ mouse.MethodsMice were randomly assigned to moderate treadmill exercise (18 m/min, 1 h, 6 days/week, 5% grade) or cage control (CC) groups from 6 to 14 weeks of age. At 12 weeks of age, mice were electroporated with either IL-6-containing or control plasmid into the quadriceps muscle. Mice were killed after 2 weeks of systemic IL-6 overexpression or control treatment.ResultsIL-6 overexpression induced an 8% loss in body weight in CC mice, which was significantly attenuated by exercise. IL-6 overexpression in CC mice increased fasting insulin and triglyceride levels, which were normalized by exercise, and associated with increased oxidative capacity, an induction of AKT signaling, and a repression of AMPK signaling in muscle. These exercise-induced changes occurred despite elevated inflammatory signaling in skeletal muscle.ConclusionWe conclude that moderate-intensity exercise can attenuate IL-6-dependent cachexia in ApcMin/+ mice, independent of changes in IL-6 concentration and muscle inflammatory signaling. The exercise effect was associated with improved insulin sensitivity and improved energy status in the muscle.

Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat

Chronic exposure to hypobaric hypoxia causes oxidative stress and neurodegeneration leading to memory impairment. The present study aimed at investigating the role of corticosterone in hypoxia induced neurodegeneration and effect of metyrapone, a corticosterone synthesis inhibitor that reduces the stress induced elevation of corticosterone without affecting the basal level, in ameliorating chronic hypobaric hypoxia induced cognitive decline. Rats were exposed to simulated altitude of 25,000 ft for 0, 3, 7, 14 and 21 days to determine the temporal alterations in corticosterone and its receptors following exposure to hypobaric hypoxia. Our results showed an elevation of corticosterone in plasma and hippocampal tissue following 7 days of exposure, which declined on prolonged hypoxic exposure for 21 days. A concomitant increase in ROS and lipid peroxidation was observed along with depletion of intracellular antioxidants. Glucocorticoid and mineralocorticoid receptors were upregulated on 3 and 7 days of hypoxic exposure. Though expression of Glut1 and Glut3 were upregulated on 3 days of hypoxic exposure, sharp decline in Glut1 expression following 7 days of hypoxic exposure leads to reduced neuronal glucose uptake. Administration of metyrapone from 3rd to 7th day of hypoxic exposure to suppress hypoxia induced increase in corticosterone levels resulted in reduced oxidative damage, neurodegeneration and improvement of intracellular energy status. The metyrapone treated hypoxic animals performed better in the Morris Water Maze. Further, administration of exogenous corticosterone along with metyrapone during hypoxic exposure blunted the neuroprotective effect of metyrapone indicating a role for corticosterone in mediating hypobaric hypoxia induced neurodegeneration and memory impairment.

Acetyl‐L‐carnitine‐mediated neuroprotection during hypoxia is attributed to ERK1/2‐Nrf2‐regulated mitochondrial biosynthesis

Neuronal damage in hypoxia and several neurodegenerative disorders is invariably associated with oxidative damage and mitochondrial dysfunction. Administration of acetyl-L-carnitine (ALCAR) on the other hand attenuates neuronal damage, prevents apoptosis, and improves energy status in hypoxic stress through less understood mechanisms. Becasue mitochondrial biogenesis could be a possible mechanism for ALCAR-induced improvement in bioenergetics in neurons, the present study aimed at exploring signaling pathways of ALCAR-induced neuroprotection in hypoxia and possible occurrence of mitochondrial biogenesis. To create global hypoxia, adult Sprague-Dawley rats were exposed to a simulated altitude of 7,620 m at standard temperature and humidity conditions. We here demonstrate that administration of ALCAR to hypoxic rats for a period of 2 weeks effectively protected hippocampal neurons from mitochondrial dysfunction, excitotoxicity, and neurodegeneration. ALCAR administration resulted in peroxisome proliferator-activated receptor γ coactivator-1α and nuclear respiratory factor-1-induced mitochondrial biogenesis, the expression of which was regulated by an extracellular-related kinase-nuclear factor erythroid 2-related factor 2 (ERK-Nrf2)-mediated mechanism. Most notably, calcium buffering into nonfunctional mitochondria ameliorated excitotoxicity and improved bioenergetic status of the hippocampal neurons. Together, the data reveal the immense therapeutic potential of ALCAR for the treatment of ischemia, stroke, and other neurodegenerative disorders associated with hypoxic stress and excitotoxicity.

Effects of α-ketoglutarate on energy status in the intestinal mucosa of weaned piglets chronically challenged with lipopolysaccharide

The present study determined whether α-ketoglutarate (AKG) might affect the expression of AMP-activated protein kinase (AMPK) and energy status in the intestinal mucosa of piglets challenged with Escherichia coli lipopolysaccharide (LPS). A total of eighteen piglets (weaned at 21d of age) were allocated to one of three treatments: (1) non-challenged (control); (2) LPS-challenged (LPS); (3) LPS+1% AKG (LPS+AKG). Piglets in the control and LPS groups were fed a maize- and soyabean meal-based diet, and the LPS+AKG group was fed the basal diet supplemented with 1% AKG. On days 10, 12, 14 and 16 of the trial, piglets in the LPS and LPS+AKG groups were challenged with LPS (80μg/kg body weight), whereas piglets in the control group received the same volume of sterile saline. Pigs were euthanised 24h after the last administration of LPS or saline to obtain intestinal mucosae for biochemical analysis. Compared with the control group, LPS administration decreased (P<0·05) the oxidation of AKG, oleic acid, glutamine and glucose in enterocytes, decreased concentrations of ATP in the duodenal and jejunal mucosae and decreased adenylate energy charge (AMP:ATP ratio) in the jejunal and ileal mucosae. Additionally, LPS treatment reduced (P<0·05) mucosal concentrations of phosphorylated AMPK in the jejunum and ileum as well as acetyl-CoA carboxylase in all segments of the small intestine. The adverse effects of LPS were reversed by AKG. Collectively, these results indicate that dietary supplementation with 1% AKG beneficially modulates the AMPK signalling pathway to improve energy status in the small intestine of LPS-challenged piglets.

Effects of caffeic acid phenethyl ester on endotoxin‐induced cardiac stress in rats: A possible mechanism of protection

Endotoxins (lipopolysaccharides; LPS) are known to cause multiple organ failure, including myocardial dysfunction. The present study aimed to investigate the mechanism of caffeic acid phenethyl ester (CAPE) protection against LPS-induced cardiac stress. Rats were allocated into three groups; group 1 served as a normal control group, group 2 (LPS) received a single intraperitoneal injection of LPS (10 mg/kg), group 3 (LPS + CAPE) was injected intraperitoneally with CAPE (10 mg/kg/day; solubilized in saline containing 20% tween 20) throughout a period of 10 days prior to LPS injection. Rats were maintained 4 h before sacrifice. Caffeic acid phenethyl ester pretreatment normalized LPS-enhanced activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH) as well as glutathione peroxidase (GPx), and myeloperoxidase (MPO) in cardiac tissue. A significant reduction of the elevated levels of serum tumor necrosis factor-alpha (TNF-α) as well as serum and cardiac nitrite/nitrate (NOx) ) was achieved after CAPE pretreatment. CAPE also restored malondialdelyde (MDA), reduced glutathione (GSH), and cytosolic calcium (Ca2+ ) levels in the heart. A marked induction of cardiac heme oxygenase-1 (HO-1) protein level was detected in CAPE-pretreated group. Whereas, LPS-induced reduction of adenosine triphosphate (ATP) and phosphocreatine (PCr) levels was insignificantly changed. Conclusively, the early treatment with CAPE maintained antioxidant defences, reduced oxidative injury, cytokine damage, and inflammation but did not markedly improve energy status in cardiac tissue. The beneficial effect of CAPE might be mediated, at least in part, by the superinduction of HO-1.

Regulation on Energy Metabolism and Protection on Mitochondria ofPanax GinsengPolysaccharide

Panax ginseng C A Meyer (PG) is one of the most popular qi-invigorating herbal medicine and has been used to promote health, vitality, and longevity in China. Although PG has been used in traditional Chinese medicine for millennia, its qi-invigorating activities still lack convincing evidence. We investigated the effects of Panax ginseng polysaccharide (PGP) on energy metabolism and mitochondrial protection. The chronic hypoxia model was set up. Lipid peroxidation product malondialdehyde (MDA) was assayed by thiobarbituric acid (TBA) colorimetry. Mice liver mitochondria were isolated by differential centrifugation. The spectrophotometric method was used to measure the swelling of mitochondria. The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in liver cells were determined by reversed-phase high performance liquid chromatography (RP-HPLC), adenylate energy charge (AEC), total adenylate pool (TAP), ATP/ADP and ATP/AMP ratio were calculated. The creatine kinase (CK) activities in mice skeletal muscle were determined by a commercial monitoring kit. The result showed that PGP could inhibit mitochondrial injury and swelling induced by Fe(2+)-L-Cys in a concentration-dependent manner. PGP which was administered by oral gavage daily for 10 days could inhibit the formation of MDA in mice brain, increase levels of ATP, ADP, TAP and AEC, ratio of ATP/ADP and ATP/AMP in liver cells, increase CK activities in mice skeletal muscle under chronic hypoxia condition. These results indicate that PGP protect mitochondria by inhibiting mitochondrial swelling, and improving energy metabolism. PGP functions as a preventive antioxidant by increasing CK activities. Therefore, PGP had the pharmaceutical activities of antihypoxia, antioxidation and improving energy status.

Effects of feeding propylene glycol on dry matter intake, lactation performance, energy balance and blood metabolites in early lactation dairy cows

The objectives of this study were to evaluate effects of feeding propylene glycol (PG) on feed intake, milk yield and milk composition, blood metabolites and energy balance in Holstein dairy cows from 1 to 63 days in milk. Thirty-two multiparous cows, blocked by lactation number, previous 305-day milk production and expected calving date, were arranged into four groups in a randomized block design. Treatments were: control, low PG, medium PG and high PG with 0, 150, 300 and 450 ml PG per cow per day, respectively. The supplement of food grade PG (0.998 g/g PG) was hand-mixed into the top one-third of the daily ration. Cows were fed ad libitum a total mixed ration consisting of forage and concentrate (50 : 50, dry matter basis). Feed intake, milk yield and milk components were not affected (P > 0.05) by PG supplementation. Overall, body weight (BW) loss tended (P < 0.08) to be linearly reduced, and energy status was linearly improved with increasing PG supplementation. Concentrations of glucose in plasma were higher for cows fed PG relative to control (55.6 v. 58.9 mg/dl) and linearly increased (P < 0.01) with increasing PG supplementation. Plasma concentrations of non-esterified fatty acids and beta-hydroxybutyrate were linearly increased, but urine acetoacetate concentration was quadratically changed with the highest for control diet and the lowest for 450 ml/day of PG. These results indicated that supplementation of PG in the early lactating cow diets had minimal effects on feed intake and milk production, but may potentially reduce contents of milk fat and milk protein. Supplementation of early lactating dairy cow diets with PG is beneficial in terms of improving energy status and reducing BW loss.

Strategies to improve fertility of high yielding dairy farms: Management of the dry period

Reproductive performance of dairy cattle has been related to a wide variety of indicators of energy status, e.g., extent of negative energy balance, time of energy balance nadir, body weight loss, body condition score, and body condition score loss. Energy balance begins to decrease during the last few weeks prior to calving primarily due to a 30–35% reduction in feed intake. Cows typically remain in negative energy balance for five to seven weeks postpartum. Nutritional strategies to improve energy balance during the transition period include fat supplementation and feeding additional nonfiber carbohydrate. Unfortunately, neither approach is likely to markedly enhance energy status, although fat supplementation may increase reproductive efficiency independent of any effect on energy balance. Alternative management strategies may be required to improve fertility of dairy cows. Shortening or eliminating the dry period may improve energy status of dairy cows and increase reproductive efficiency. Shortening or eliminating the dry period may enhance dry matter intake during the transition period, decrease milk energy output, or both. A preliminary study using small animal numbers indicated that reducing dry period length to 28 or 0 days may decreases days to first ovulation, increase first service conception rate, and decrease days open. A follow-up study employing large animal numbers confirmed that reducing dry period length from 55 to 34 days can decrease days to first ovulation and decrease the percentage of anovular cows. The reduction in days open was greater for older cows than second parity cows. The reduction in days open was not related to effects of treatment on milk yield. Shortening or eliminating the dry period may be a more successful approach to improving reproductive efficiency than diet manipulation.

Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone

Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy. Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively. In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls. The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning.

Nicotinamide Reverses Neurological and Neurovascular Deficits in Streptozotocin Diabetic Rats

In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues. We report the dose-dependent effects of nicotinamide in an established model of early DPN. Control and streptozotocin-diabetic rats were treated with 200 to 400 mg/kg/day nicotinamide (i.p.) for 2 weeks after 2 weeks of untreated diabetes. Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and hydrogen clearance, and sciatic motor and hind-limb digital sensory nerve conduction velocities and thermal and mechanical algesia were measured by standard electrophysiological and behavioral tests. Malondialdehyde plus 4-hydroxyalkenal concentration in the sciatic nerve and amino acid-(4)-hydroxynonenal adduct and poly(ADP-ribosyl)ated protein expression in human Schwann cells were assessed by a colorimetric method with N-methyl-2-phenyl indole and Western blot analysis, respectively. Nicotinamide corrected increased sciatic nerve lipid peroxidation in concert with nerve perfusion deficits and dose-dependently attenuated nerve conduction slowing, as well as mechanical and thermal hyperalgesia. Nicotinamide (25 mM) prevented high (30 mM) glucose-induced overexpression of amino acid-(4)-hydroxynonenal adducts and poly(ADP-ribosyl)ated proteins in human Schwann cells. In conclusion, nicotinamide deserves consideration as an attractive, nontoxic therapy for the treatment of DPN.

AMPK and metabolic adaptation by the heart to pressure overload

Accelerated glycolysis in hypertrophied hearts may be a compensatory response to reduced energy production from long-chain fatty acid oxidation with 5'-AMP-activated protein kinase (AMPK) functioning as a cellular signal. Therefore, we tested the hypothesis that enhanced fatty acid oxidation improves energy status and normalizes AMPK activity and glycolysis in hypertrophied hearts. Glycolysis, fatty acid oxidation, AMPK activity, and energy status were measured in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague-Dawley rats. Hearts from halothane (3-4%)-anesthetized rats were perfused with KH solution containing either palmitate, a long-chain fatty acid, or palmitate plus octanoate, a medium-chain fatty acid whose oxidation is not impaired in hypertrophied hearts. Compared with control, fatty acid oxidation was lower in hypertrophied hearts perfused with palmitate, whereas it increased to similar values in both groups with octanoate plus palmitate. Glycolysis was accelerated in palmitate-perfused hypertrophied hearts and was normalized in hypertrophied hearts by the addition of octanoate. AMPK activity was increased three- to sixfold with palmitate alone and was reduced to control values by octanoate plus palmitate. Myocardial energy status improved with the addition of octanoate but did not differ between groups. Our findings, particularly the correspondence between glycolysis and AMPK activity, provide support for the view that activation of AMPK is responsible, in part, for the acceleration of glycolysis in cardiac hypertrophy. Additionally, they indicate myocardial AMPK is activated by energy state-independent mechanisms in response to pressure overload, demonstrating AMPK is more than a sensor of the heart's energy status.

Control of glycolysis in pathologic cardiac hypertrophy

5′-AMP activated protein kinase (AMPK), whose activation by a low energy status due to impaired long-chain fatty acid oxidation, may be responsible for acceleration of glycolysis in pathologic cardiac hypertrophy. Therefore, we determined if enhanced fatty acid oxidation would improve energy status and normalize AMPK activity and glycolysis in hypertrophied hearts. Glycolysis, fatty acid oxidation, AMPK activity, and high energy phosphates were measured in isolated working hypertrophied (HYP) and control (CON) hearts from aortic-constricted and sham-operated male rats. Hearts were perfused with Krebs-Henseleit solution containing 5.5mM [5-3H]-glucose, 0.5mM lactate, 100mU/L insulin and either 1.2mM [1-14C]-palmitate (P) or a combination of [1-14C]-octanoate (1.2mM) and [9,10-3H]-palmitate (0.6mM) (O-P). Compared to CON, fatty acid oxidation was not different in HYP perfused with O-P but was ∼37 % lower in HYP perfused with P (p<0.05). Glycolysis was normalized in HYP by O-P perfusion and was accelerated ∼59 % in HYP perfused with P (p<0.05). AMPK activity, which was 70 % higher than CON in HYP perfused with P (P<0.05), no longer differed between CON and HYP perfused with O-P. Energy status did not differ between CON and HYP, although it was improved in hearts perfused with O-P. These findings are consistent with the view that activation of AMPK is responsible, at least in part, for the acceleration of glycolysis in pathologic cardiac hypertrophy. However, AMPK activation occurs in hypertrophied hearts occurs in the absence of measurable changes in energy status suggesting other mechanisms are responsible.

Supplementation of L-carnitine Improves Mitochondrial Enzymes in Heart and Skeletal Muscle of Aged Rats

Aging is characterized by a general decline in physiological functions that affects many tissues and increases the risk of death. Deterioration of mitochondria, the major source and target of reactive oxygen species (ROS), is implicated in aging and a variety of age-related diseases. In the present study, the activities of citric acid cycle enzymes, such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase, were found to be decreased in aged rats as well as that of electron-transferring enzymes such as NADH dehydrogenase and cytochrome c oxidase. After supplementation of carnitine to aged rats, the activities of these enzymes reverted nearer to that of young control rats. These findings suggest that L-carnitine improves the activities of mitochondrial enzymes, increases the electron flow through the electron transport chain, and improves reducing equivalence, thereby improves energy status in aged rats.