Increase In Non-esterified Fatty Acids Research Articles

Dynamic of Metabolic Indicators, Insulin Like-growth Factor I (IGF-I) and Cortisol in Holstein Cows during the Transition Period

Background: Physiological events occur in the transition period marked by negative energetic balance, where the energetic demand is higher due to fetal nutrition and lactogenesis and intensified by the decrease of the dry matter intake in the pre-partum period. The adaptation of cows is dependent of homeostatic and homeorhetic mechanisms regulated by catecholamine, cortisol, GH, IGF-I, insulin and glucagon but the priorization of homeorhetic mechanisms could result in metabolic diseases. Considering the scarce longitudinal studies about the Brazilian conditions the aim of this project was to evaluate the influence of transition period on metabolic indicators, cortisol and IGF-I in Holstein cows.Materials, Methods & Results: Thirteen cows, from 2nd to 4th lactation were evaluated weakly from week -2 to week +3 in relation to calving to determine the body condition score (BCS), metabolic and endocrine profile. The BCS decreased between week -2 (BCS = 4.0) and +1 (BCS = 3.0), followed by and slight increase on weeks +2 and +3 (P = 0.000). The most of metabolic indicators and hormones have changed during the transition period (P ≤ 0.05), especially around calving. It was possible to detect the peak of cortisol, glucose, non-esterified fatty acids (NEFA), ß-hydroxibutyrate (BHB), and aspartate aminotransferase (AST) on delivery and week +1. On the other hand, total calcium, triglycerides (TG) and cholesterol (CHOL) decreased was observed around parturition. Insulin like growth factor type I (IGF-I) showed marked reduction between pre and postpartum, and the lowest value was observed in the week +1. TP and GLOB had the lowest value on calving and globulin has a gradual increase from delivery to week +3.Discussion: Cows included in this experiment had dystocia (4/13, 30.8%), retention of placenta (1/13, 7.7%) and clinical hypocalcemia (1/13, 7.7%). One of the animals with episodes of dystocia was also aggravated by ketosis in week +1 and +2 (1/13, 7.7%). Uterine infections were observed in five animals (5/13, 38.4%). Of this total of animals with uterine infection (5/13), three had already expressed earlier disturbances: two cows had dystocia and one cow with retention of placenta. The weight loss observed between pre and postpartum may be due to an increase of energy demand for fetal maintenance and the concomitant initiation of lactation, in conjunction with an approximately 30% reduction in dry matter intake during the transitional period. The hyperglycemia concomitant with the peak of cortisol at delivery may be explaining by the activation of the somatotropic axis, due to the stress of calving. The increase of NEFA, BHB and AST around calving associated with decreased of TG and CHOL could be associated with homeorhetic mechanisms, especially lipolysis and gluconeogenesis. The IGF-I decrease in postpartum may be by the decreased expression of receptors for growth hormone (GH) in the liver, and consequently reduced synthesis and/or IGF-I hepatic clearance, which reduce of the negative feedback of IGF-I on GH secretion. The total calcium concentrations were below the threshold (8.50 mg/dL) established by Goff [10] at parturition, week +1 and +2 and probably is due to the secretion of 20-30 g of calcium per day during the colostrum synthesis. Total protein and albumin have a slight variation, except for the peak observed on week +3 due to uterine infection.

No effect of acute normobaric hypoxia on plasma triglyceride levels in fasting healthy men.

Circulating fatty acids are a major systemic energy source in the fasting state as well as a determinant of hepatic triglycerides (TG)-rich very-low-density lipoprotein production. Upon acute hypoxia, sympathetic arousal induces adipose tissue lipolysis, resulting in an increase in circulating nonesterified fatty acids (NEFA). Animal studies suggest that TG clearance may also be strongly reduced under hypoxia, though this effect has been shown to be dependent on temperature. Whether the hypoxia-induced rise in blood fatty acid concentrations affects fasting TG levels in humans under thermoneutral conditions remains unknown. TG, NEFA, and glycerol levels were measured in fasted healthy young men (n = 10) exposed for 6 h to either normoxia (ambient air) or acute hypoxia (fraction of inspired oxygen = 0.12) in a randomized, crossover design. Participants were casually clothed and rested in front of a fan in an environmental chamber maintained at 28 °C during each trial. Under hypoxia, a significantly greater increase in NEFA occurred (condition × time interaction, p = 0.049) and glycerol levels tended to be higher (condition × time, p = 0.104), suggesting an increase in adipose tissue lipolysis. However, plasma TG levels did not change over time and did not differ between the normoxia and hypoxia conditions. In conclusion, acute exposure to normobaric hypoxia under thermoneutral condition in healthy men during fasting state increased lipolysis without affecting circulating TG.

Lipoliza i ketogeneza kod krava u ranoj laktaciji

Peripartal metabolic stress is characterized by increased lipid mobilization, when non-esterified fatty acids (NEFA) are increased, as well as by increased ketogenesis, when the concentration of beta-hydroxybutyrate (BHB) is increased. NEFA are metabolized in all tissues but the main organ is the liver. Possible processes are: a) complete oxidation of NEFA, b) partial oxidation and synthesis of ketone bodies (BHB), c) development of triglycerides from NEFA that can be transported or stay in the liver when fatty liver is apparent. Moreover, increased lipolysis and ketogenesis can cause oxidative stress because concentrations of MDA and/or TBARS are positively correlated with NEFA and BHB concentrations. The increase in NEFA during the peripartal period affects the cellular immunologic response by changing intracellular signals, gene expressing control, activation of transcriptional factors, apoptosis induction and by modifying mediators of lipid production. Increased proportion of cows with high NEFA and BHB concentrations in the herd can cause reduced milk yield at the end of a standard 305-day lactation. NEFA concentrations can be related to postpartal ovarian activity, especially given that blood NEFA concentrations represent NEFA concentrations in the ovarian follicular fluid. Cows on farms with lower scores of animal welfare and nutrition have higher concentrations of cortisol, NEFA, BHB, bilirubin, glucose and urea. NEFA and BHB concentrations in early lactation can be used for estimating metabolic adaptation in the first 8 weeks after calving. For the estimation of metabolic adaptation, increased lipolysis has a greater significance than decreased anabolic parameters.

Long-term adaptation capacity of ponies: effect of season and feed restriction on blood and physiological parameters

Domesticated horses are increasingly kept under semi-natural housing conditions, whereas their adaptation capacity is not fully investigated. In all, 10 Shetland pony mares were held under semi-extensive conditions for 1 year. In winter animals were allocated into two feeding groups (60% and 100% of maintenance energy requirement, respectively). Triiodothyronine, thyroxine, non-esterified fatty acids (NEFA), total bilirubin, total protein, triglyceride, glucose, insulin and hair length were measured at monthly intervals, whereas BW, body condition score, cresty neck score and resting heart rate were recorded every 2 weeks. From summer to winter all Ponies showed a reduction in resting heart rate (P<0.001) and triiodothyronine (P<0.001) but an increase in NEFA (P<0.001), thyroxine (P<0.001) and triglyceride (P<0.001) concentrations. Feed restriction led to a reduced resting heart rate (P=0.009), increased NEFA (P<0.001) and total bilirubin (P=0.008) concentrations. Thyroid hormones did not differ between feeding groups (P>0.05). Refeeding of restrictively fed ponies resulted in a rapid increase in resting heart rate and BW and a return of blood parameters to reference values. Adequately supplied animals adapted without difficulty to varying environmental conditions, whereas feed restriction in ponies during winter resulted in reduced resting heart rates suggesting a reduced basal metabolic rate. The energy restriction was compensated by mobilizing body fat reserves which led to changes in blood parameters. Refeeding in feed restricted animals revealed a remarkably quick recovery of physiological and blood parameters to reference values. We therefore suggest that year round-outdoor housing can be a suitable housing system for robust horse breeds provided that an adequate food supply is available.

Metabolic and Ruminal Fluid Markers of Dairy Cows Supplemented with a Combination of Yeast Culture and Hydrolyzed Yeast

Background: In order to reduce the effects of a negative energy balance, some measures have been taken into account in nutritional management during the transition period. The use of yeast, has been a good alternative used to improve the rumen metabolism and helping the adjustment of the microbiotato the new diet. The aim of the study was to evaluate the effects of supplementing a combination of yeast culture and hydrolyzed yeast on the metabolism of dairy cows during the transition period.Materials, Methods &amp; Results: The experiment was conducted in a semi-extensive system, using 20 Holstein cows, divided equally into a control group (CG) and a supplemented group (SG). The SG received 28 g/animal/day of a combination of yeast culture and hydrolyzed yeast from 20 ± 2 days pre-calving until early lactation (18 ± 3 days). Serum concentrations of non-esterified fatty acids (NEFA), albumin and urea were determined at calving, and for three time points during the early postpartum period and three time points during the early lactation period. Regarding energy metabolism, prepartum concentrations of NEFA were higher than the physiological standard in both groups. However, NEFA, albumin and urea decreased during the early postpartum period in the supplemented animals and could be attributed to the yeast in enhancing ruminal microorganisms’ cellulolytic capacity, increasing fibre digestibility and starch utilization.Discussion: The increased concentration of non-esterified fatty acids (NEFA) due to the mobilization of fat deposits that happens in the transition period, especially in the postpartum period reflects the cow’s adaptation to the negative energy balance (NEB). The lower concentrations of NEFA observed in the present study could be attributed to the effect of the yeast in enhancing the ruminal microorganisms’ cellulolytic capacity. The control cows had a BCS within the recommended range while the supplemented group had it close to the minimal limit proposed for this period. Thus, supplemented cows lost less BCS during the early postpartum period, had a lower BCS loss during the experimental period and had lower NEFA concentration that the CG. It was possible to observe a difference in serum albumin and urea between treatments only in the postpartum period. Besides showing no significant effect in BCS on prepartum period, control cows had a BCS within the recommended range while the supplemented group had it close to the minimal limit proposed for this period. Cows with high BCS prepartum had higher plasma NEFA before and after calving. It can be observed in the present study in both groups. However, a positive effect in prevent subclinical disorders might be attributed to YC, since the SG showed low NEFA plasma levels compared to the CG. Thus, supplemented cows lost less BCS during the early postpartum period, had a lower BCS loss during the experimental period and had lower NEFA concentration that the CG. There is a negative correlation between BCS and NEFA in the early postpartum period and this information explains the results observed in the present study where BCS declines in the SG are followed by a NEFA increase. This is not so marked in the CG, indicating that SG supplementation can act by improving digestibility. Yeast supplementation promotes higher output energy, enhancing postpartum performance in dairy cows. Yeast supplementation showed benefits in early lactation compared to the prepartum and early postpartum periods, suggesting that supplementation has to have an adaptation period to be effective in protein synthesis. In conclusion, supplementation with a combination of yeast culture and hydrolyzed yeast to cows during the transition period can positively influence the energy and protein metabolism, reducing the collateral effects of negative energy balance.

Regular activity breaks combined with physical activity improve postprandial plasma triglyceride, nonesterified fatty acid, and insulin responses in healthy, normal weight adults: A randomized crossover trial

Compared with prolonged sitting, regular activity breaks immediately lower postprandial glucose and insulin, but not triglyceride responses. Postprandial triglycerides can be lowered by physical activity but the effect is often delayed by ∼12 to 24hours. The objective of the study was to determine whether regular activity breaks affect postprandial triglyceride response in a delayed manner similar to physical activity. In a randomized crossover trial, 36 adults (body mass index 23.9kg/m2 [standard deviation 3.9]) completed four 2-day interventions: (1) prolonged sitting (SIT); (2) prolonged sitting with 30minutes of continuous walking (60% VO2max), at the end of Day 1 (SIT+PAD1); (3) Sitting with 2minutes of walking (60% VO2max) every 30minutes (RAB); (4) A combination of the continuous walking and regular activity breaks in 2 and 3 above (RAB+PAD1). Postprandial plasma triglyceride, nonesterified fatty acids, glucose, and insulin responses were measured in venous blood over 5hours on Day2. Compared with SIT, both RAB (difference: -43.61mg/dL·5hours; 95% confidence interval [CI] -83.66 to -2.67; P=.035) and RAB+PAD1 (-65.86mg/dL·5hours; 95% CI -112.14 to -19.58; P=.005) attenuated triglyceride total area under the curve (tAUC). RAB+PAD1 produced the greatest reductions in insulin tAUC (-23%; 95% CI -12% to -31%; P<.001), whereas RAB resulted in the largest increase in nonesterified fatty acids (tAUC, 10.08mg/dL·5hours; 95% CI 5.60-14.84; P<.001). There was no effect on glucose tAUC (P=.290). Postprandial triglyceride response is attenuated by regular activity breaks, when measured ∼24hours after breaks begin. Combining regular activity breaks with 30minutes of continuous walking further improves insulinemic and lipidemic responses.

Acute Hypercortisolemia Exerts Depot-Specific Effects on Abdominal and Femoral Adipose Tissue Function.

Context:Glucocorticoids have pleiotropic metabolic functions, and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear.Objective:To provide an in vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration.Design and Outcome Measures:Nine healthy male volunteers were studied on two occasions, after a hydrocortisone infusion (0.2 mg/kg/min for 14 hours) and a saline infusion, respectively, given in randomized double-blind order. The subjects were studied in the fasting state and after a 75-g glucose drink with an in vivo assessment of femoral adipose tissue blood flow (ATBF) using radioactive xenon washout and of lipolysis and glucose uptake using the arteriovenous difference technique. In a separate study (same infusion design), eight additional healthy male subjects underwent assessment of fasting abdominal ATBF and lipolysis only. Lipolysis was assessed as the net release of nonesterified fatty acids (NEFAs) from femoral and abdominal subcutaneous adipose tissue.Results:Acute hypercortisolemia significantly increased basal and postprandial ATBF in femoral adipose tissue, but the femoral net NEFA release did not change. In abdominal adipose tissue, hypercortisolemia induced substantial increases in basal ATBF and NEFA release.Conclusions:Acute hypercortisolemia induces differential lipolysis and ATBF responses in abdominal and femoral adipose tissue, suggesting depot-specific glucocorticoid effects. Abdominal, but not femoral, adipose tissue contributes to the hypercortisolemia-induced systemic NEFA increase, with likely contributions from other adipose tissue sources and intravascular triglyceride hydrolysis.

Thermal stability of human plasma electronegative low-density lipoprotein: A paradoxical behavior of low-density lipoprotein aggregation

Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(−), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(−). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(−) aggregated and fused faster than LDL(+), but later the order reversed. Most LDL(+) disintegrated and precipitated upon prolonged heating. In contrast, LDL(−) partially retained lipoprotein morphology and formed soluble aggregates. Biochemical analysis of all fractions showed no significant degradation of major lipids, mild phospholipid oxidation, and an increase in non-esterified fatty acid (NEFA) upon thermal denaturation. The main baseline difference between LDL subfractions was higher content of NEFA in LDL(−). Since NEFA promote lipoprotein fusion, increased NEFA content can explain rapid initial aggregation and fusion of LDL(−) but not its resistance to extensive disintegration. Partial hydrolysis of apoB upon heating was similar in LDL subfractions, suggesting that minor proteins importantly modulate LDL disintegration. Unlike LDL(+), LDL(−) contains small amounts of apoA-I and apoJ. Addition of exogenous apoA-I to LDL(+) hampered lipoprotein aggregation, fusion and precipitation, while depletion of endogenous apoJ had an opposite effect. Therefore, the initial rapid aggregation of LDL(−) is apparently counterbalanced by the stabilizing effects of minor proteins such as apoA-I and apoJ. These results help identify key determinants for LDL aggregation, fusion and coalescence into lipid droplets in vivo.

Lipid and Lipoprotein Profiles Modification in Athletic Horses After Repeated Jumping Events

The aim of this study was to evaluate the effect of physical exercise on serum nonesterified fatty acids (NEFAs), triglycerides, total cholesterol (total chol), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and very low–density lipoprotein (VLDL) fraction levels in Jumper horses. Horses took part to a show jumping competition represented by repeated events. Blood sampling was performed before the first day of competition (T0), within 10 minutes from the end of each competition (T1POST, T2POST, T3POST), and in the day after competition (R1). Statistical analysis showed a significant effect of exercise (P < .001) on all studied parameters. Nonesterified fatty acids showed higher values at T1POST, T2POST, and T3POST than T0. Higher serum triglycerides, VLDLs, and HDLs levels were found at T1POST, T2POST, T3POST, and R1 than T0. Total cholesterol and LDLs values showed a significant decrease at T1POST, T2POST, T3POST, and R1 than T0. The observed changes in lipid and lipoprotein parameters could represent the metabolic response to physical exercise during the 3 days of competition that led to an increase of NEFAs and triglycerides levels after the physical exercise which act as energy support, whereas during the recovery period, the energy production was assured by oxidation of serum triglycerides. The increase in serum HDLs, decrease in total chol, and LDLs point out the positive effects of physical exercise on the lipoproteins profile in trained horses suggesting the reverse cholesterol transport from peripheral tissues to the liver for new biochemical processes in trained Jumper horses.

Hematological Parameters in Cows in Early Lactation Treated with Ketoprofen and their Relationship with Lipid Mobilization and Ketogenesis

Background: Dairy cows are exposed to numerous hematological and biochemical changes, what is bringing cows into the state of increased metabolic activity and physiological adaptations. These adaptive processes have resulted in increased lipid mobilization and ketogenesis with increased concentration of non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB). As a non steroidal anti-inflammatory drug, ketoprofen produces anti-inflammatory effects. The main objective of the present study was to found relationship between hematological parameters and ketoprofen administration and high lipid mobilization and ketogenesis in cows treated with ketoprofen immediately after calving.Materials, Methods &amp; Results: Ketoprofen was used (3 mg/kg body weight) intramuscularly for three consecutive days post-partum on 15 cows of Holstein-Friesian breed. Cows of the control group (n = 15) were not treated with ketoprofen. Blood samples were collected at the day of calving, in the first and in the second week after parturition from the coccygeal vein of the both groups. Hematological parameters (erythrocytes, hemoglobin, neutrophils, lymphocytes and mean platelet volume) were determined on the automatic hematological counter. Metabolic parameters (NEFA, BHB) were determined by standard colorimetric kits using a semi-automatic biochemistry analyzer. Student’s t-test was used to determine the influence of the application of ketoprofen to the hematological parameters. The data analysis was performed using SPSS, version 19.0, software package for Microsoft Windows (IBM, Armonk, NY, USA). The results of comparison with (P &lt; 0.05) were considered to represent statistically significant differences. Difference in correlation test between NEFA and BHB and other blood parameters in experimental and control group of cows were determined by the Fischer r-to-z transformation. The research results show that there was a increased red blood cell count and a higher concentration of hemoglobin (P &lt; 0.05), fewer neutrophils (P &lt; 0.01), lower number of lymphocytes (P &lt; 0.01) and fewer mean platelet volume in cows that received ketoprofen after calving than those of the control. Determined hematological parameters and values of NEFA and BHB are in correlation. The correlation coefficients were significantly lower in the experimental group of cows. The intensity of the connection between hematological parameters and value of NEFA and BHB decreases.Discussion: It is well known that dairy cows with excessive adiposity manifest a low-grade inflammation and that elevated NEFA concentrations present positive risk factors for many proinflammatory diseases. Analyzing the results in this examination, it has been noticed that the increase of NEFA and BHB after calving were significantly lower in group of cows treated with ketoprofen. Also, determined hematological parameters and values of NEFA and BHB are in correlation. The intensity of these connection decreases in ketoprofen treated cows. In current study, in cows treated with ketoprofen there is decrease in concentrations of inflammatory mediators such as neutrophils and lymphocytes. Red blood cell and hemoglobin concentration decreased in the peripartal period as a result of inflammation. In cows treated with ketoprofen these concentrations increased. In many inflammatory conditions mean platelets volume is increased while there is a decrease in ketoprofen treated cows. Presented results indicate strong relationship between the concentration of NEFA, as well as BHB and hematological parameters indicating that the dependence of hematological parameters of intensity of lipid mobilization and ketogenesis was significantly lower in cows treated with ketoprofen immediately after calving.

Влияние мелатонина на изменения липидного обмена при иммобилизационном стрессе

The experiments on rats revealed the increase in non-esterified fatty acids (NEFA), cholesterol, triglycerides, and low- and high-density lipoproteins in blood plasma after immobilization stress. The injections of melatonin in the doses 0.2 and 1.0 mg/kg had no significant influence on lipid metabolism indices. The administration of hormone in both doses caused the increase in high-density lipoproteins (HDL) content 39 hours after immobilization as compared with thecontrol group. On the fourth day the decrease in NEFA concentration was observed in blood plasma of rats which had been injected with melatonin in the dose 1.0 mg/kg as compared with the control group. Lower LDL concentration as compared to the control group was revealed after melatonin administration in the dose 0.2 mg/kg. The increase in LDL concentration in rats having received melatonin in the dose 1.0 mg/kg was observed on the seventh day after immobilization.

Abundance of ruminal bacteria, epithelial gene expression, and systemic biomarkers of metabolism and inflammation are altered during the peripartal period in dairy cows

Seven multiparous Holstein cows with a ruminal fistula were used to investigate the changes in rumen microbiota, gene expression of the ruminal epithelium, and blood biomarkers of metabolism and inflammation during the transition period. Samples of ruminal digesta, biopsies of ruminal epithelium, and blood were obtained during −14 through 28d in milk (DIM). A total of 35 genes associated with metabolism, transport, inflammation, and signaling were evaluated by quantitative reverse transcription-PCR. Among metabolic-related genes, expression of HMGCS2 increased gradually from −14 to a peak at 28 DIM, underscoring its central role in epithelial ketogenesis. The decrease of glucose and the increase of nonesterified fatty acids and β-hydroxybutyrate in the blood after calving confirmed the state of negative energy balance. Similarly, increases in bilirubin and decreases in albumin concentrations after calving were indicative of alterations in liver function and inflammation. Despite those systemic signs, lower postpartal expression of TLR2, TLR4, CD45, and NFKB1 indicated the absence of inflammation within the epithelium. Alternatively, these could reflect an adaptation to react against inducers of the immune system arising in the rumen (e.g., bacterial endotoxins). The downregulation of RXRA, INSR, and RPS6KB1 between −14 and 10 DIM indicated a possible increase in insulin resistance. However, the upregulation of IRS1 during the same time frame could serve to restore sensitivity to insulin of the epithelium as a way to preserve its proliferative capacity. The upregulation of TGFB1 from −14 and 10 DIM coupled with upregulation of both EGFR and EREG from 10 to 28 DIM indicated the existence of 2 waves of epithelial proliferation. However, the downregulation of TGFBR1 from −14 through 28 DIM indicated some degree of cell proliferation arrest. The downregulation of OCLN and TJP1 from −14 to 10 DIM indicated a loss of tight-junction integrity. The gradual upregulation of membrane transporters MCT1 and UTB to peak levels at 28 DIM reflected the higher intake and fermentability of the lactation diet. In addition, those changes in the diet after calving resulted in an increase of butyrate and a decrease of ruminal pH and acetate, which partly explain the increase of Anaerovibrio lipolytica, Prevotella bryantii, and Megasphaera elsdenii and the decrease of fibrolytic bacteria (Fibrobacter succinogenes, Butyrivibrio proteoclasticus). Overall, these multitier changes revealed important features associated with the transition into lactation. Alterations in ruminal epithelium gene expression could be driven by nutrient intake–induced changes in microbes; microbial metabolism; and the systemic metabolic, hormonal, and immune changes. Understanding causes and mechanisms driving the interaction among ruminal bacteria and host immunometabolic responses merits further study.

Hepatic lipidosis in high-yielding dairy cows during the transition period: haematochemical and histopathological findings

The aim of this study was to assess the severity and distribution of hepatic lipidosis in high-yielding dairy cows during the transition period by the evaluation of body condition score (BCS), serum levels of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) and histological liver lipid content (GdL). Twenty-seven dairy cows, with a milk production of ~10 000 kg per year were enrolled in an experiment. Clinical examination was performed to evaluate the health status or the presence of periparturient diseases after calving. Animals were divided into two groups: healthy (HG; n = 11) and sick (SG; n = 16). The evaluation of BCS, NEFA, BHB and liver biopsies were performed at 15 ± 5 days prepartum (T0), 10 ± 2 days postpartum (T1), 30 ± 2 days postpartum (T2) and 50 ± 2 days postpartum (T3). Two-way repeated-measure ANOVA was applied to assess statistical significance of sampling time and between groups for all variables. Pearson’s correlation coefficient was used to investigate the relationship between all variables. Results showed BCS loss from T0 to T3 in SG and a significant increase of NEFA and BHB at T1. The GdL began to be mild at T0 increasing and becoming moderate to severe at T1, fairly regressing, but not disappearing, at T2 and T3, in both groups. This study showed that high lipomobilisation with a mild to moderate fat infiltration does not imply that ketosis or other periparturient diseases might be present. Our results suggest that hepatic lipidosis is associated with long-term histological and metabolic changes in dairy cows.

Associations between hepatic metabolism of propionate and palmitate in liver slices from transition dairy cows

Multiparous Holstein cows (n=95) were used to evaluate changes in hepatic propionate and palmitate metabolism and liver composition over time during the transition period, along with the relationships of these variables with cumulative increases in nonesterified fatty acids and β-hydroxybutyrate during the periparturient period. Data from 3 previous experiments were used to address the study objectives, accounting for a total of 95 multiparous Holstein cows. Liver slices from biopsies on d −21, 1, and 21 relative to parturition were used to determine conversion of [1-14C]palmitate to CO2 and esterified products (EP) and the conversion of [1-14C]propionate to CO2 and glucose. Hepatic glycogen content was highest on d −21 and was 26.9 and 36.5% of prepartum values on d 1 and 21, respectively. Liver triglyceride content was lowest at d −21 and was 271 and 446% of prepartum values on d 1 and 21, respectively. We detected no difference in the capacity for the liver to oxidize [1-14C]palmitate to CO2 between d −21 and d 1; however, on d 21, oxidation was 84% of prepartum values. The capacity of the liver to convert [1-14C]palmitate to EP was 148 and 139% of prepartum values on d 1 and 21, respectively. The capacity of liver to convert [1-14C]propionate to CO2 was 127 and 83% of prepartum values on d 1 and 21, and the capacity of liver to convert [1-14C]propionate to glucose was 126 and 85% of prepartum values on d 1 and 21, respectively. Correlation relationships suggest that overall, cows with elevated prepartum liver triglyceride content had elevated triglycerides throughout the transition period along with increased [1-14C]palmitate oxidation and conversion to EP and a decreased propensity to convert [1-14C]propionate to glucose. Cows with increased [1-14C]propionate oxidation had increased conversion of [1-14C]propionate to glucose throughout the transition period. Overall, conditions that lead to impairments in fatty acid metabolism during the transition period appear to be associated with impaired postpartum hepatic propionate metabolism.

Nonesterified fatty acids, albumin, and platelet aggregation.

It has been known for five decades that nonesterified fatty acids (NEFAs) have a role in the activation of platelets and thrombosis. Thus, the infusion of NEFAs leads to massive thrombosis and platelet activation (1–4). It has also been shown that their binding to albumin protects the platelets from activation (5). Thus, it follows that a fall in the concentrations of albumin, as in the nephrotic syndrome, would potentially lead to platelet activation. This has been demonstrated in several studies (6). Similarly, any condition that leads to an increase in NEFAs or a decrease in plasma albumin concentrations or a combination of the two would contribute to platelet hyperactivity. Insulin is a potent antilipolytic hormone and thus insulin-resistant states are characterized by accelerated lipolysis and increased NEFA concentrations. This promotes platelet aggregation. In addition, elevated NEFA concentrations interfere with insulin signal transduction and induce insulin resistance (7). NEFAs also induce oxidative and inflammatory stress (8) and thus activate monocytes, which express the prothrombotic tissue factor (TF) on their cell membranes (9). TF activates the extrinsic pathway of thrombin generation and hence may precipitate thrombosis. Activated platelets in patients with diabetes and …

Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men.

Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering. Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men. Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized. Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold-defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U-(13)C]-palmitate and [3-(3)H]-glucose tracer methodologies coupled with positron emission tomography using (11)C-acetate and (18)F-fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold-induced increase in whole-body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 ± 124 vs. 12 ± 8 μmol min(-1), respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WAT lipolysis is closely associated with BAT metabolic activation upon acute cold exposure in healthy men. In humans, muscle glucose utilization during shivering contributes to a much greater extent than BAT to systemic glucose utilization during acute cold exposure.

A thyroid hormone challenge in hypothyroid rats identifies T3 regulated genes in the hypothalamus and in models with altered energy balance and glucose homeostasis.

The thyroid hormone triiodothyronine (T3) is known to affect energy balance. Recent evidence points to an action of T3 in the hypothalamus, a key area of the brain involved in energy homeostasis, but the components and mechanisms are far from understood. The aim of this study was to identify components in the hypothalamus that may be involved in the action of T3 on energy balance regulatory mechanisms. Sprague Dawley rats were made hypothyroid by giving 0.025% methimazole (MMI) in their drinking water for 22 days. On day 21, half the MMI-treated rats received a saline injection, whereas the others were injected with T3. Food intake and body weight measurements were taken daily. Body composition was determined by magnetic resonance imaging, gene expression was analyzed by in situ hybridization, and T3-induced gene expression was determined by microarray analysis of MMI-treated compared to MMI-T3-injected hypothalamic RNA. Post mortem serum thyroid hormone levels showed that MMI treatment decreased circulating thyroid hormones and increased thyrotropin (TSH). MMI treatment decreased food intake and body weight. Body composition analysis revealed reduced lean and fat mass in thyroidectomized rats from day 14 of the experiment. MMI treatment caused a decrease in circulating triglyceride concentrations, an increase in nonesterified fatty acids, and decreased insulin levels. A glucose tolerance test showed impaired glucose clearance in the thyroidectomized animals. In the brain, in situ hybridization revealed marked changes in gene expression, including genes such as Mct8, a thyroid hormone transporter, and Agrp, a key component in energy balance regulation. Microarray analysis revealed 110 genes to be up- or downregulated with T3 treatment (± 1.3-fold change, p<0.05). Three genes chosen from the differentially expressed genes were verified by in situ hybridization to be activated by T3 in cells located at or close to the hypothalamic ventricular ependymal layer and differentially expressed in animal models of long- and short-term body weight regulation. This study identified genes regulated by T3 in the hypothalamus, a key area of the brain involved in homeostasis and neuroendocrine functions. These include genes hitherto not known to be regulated by thyroid status.

Blood immunometabolic indices and polymorphonuclear neutrophil function in peripartum dairy cows are altered by level of dietary energy prepartum

Cows experience some degree of negative energy balance and immunosuppression around parturition, making them vulnerable to metabolic and infectious diseases. The effect of prepartum feeding of diets to meet (control, 1.34Mcal/kg of dry matter) or exceed (overfed, 1.62Mcal/kg of dry matter) dietary energy requirements was evaluated during the entire dry period (∼45 d) on blood polymorphonuclear neutrophil function, blood metabolic and inflammatory indices, and milk production in Holstein cows. By design, dry matter intake in the overfed group (n=9) exceeded energy requirements during the prepartum period (−4 to −1 wk relative to parturition), resulting in greater energy balance when compared with the control group (n=10). Overfed cows were in more negative energy balance during wk 1 after calving than controls. No differences were observed in dry matter intake, milk yield, and milk composition between diets. Although nonesterified fatty acid concentration pre- (0.138mEq/L) and postpartum (0.421mEq/L) was not different between diets, blood insulin concentration was greater in overfed cows prepartum (16.7μIU/mL) compared with controls pre- and postpartum (∼3.25μIU/mL). Among metabolic indicators, concentrations of urea (4.63 vs. 6.38mmol/L), creatinine (100 vs. 118μmol/L), and triacylglycerol (4.0 vs. 8.57mg/dL) in overfed cows were lower prepartum than controls. Glucose was greater pre- (4.24 vs. 4.00mmol/L) and postpartum (3.49 vs. 3.30mmol/L) compared with control cows. Among liver function indicators, the concentration of bilirubin increased by 2 to 6 fold postpartum in control and overfed cows. Phagocytosis capacity of polymorphonuclear neutrophils was lower prepartum in overfed cows (32.7% vs. 46.5%); phagocytosis in the control group remained constant postpartum (50%) but it increased at d 7 in the overfed group to levels similar to controls (48.4%). Regardless of prepartum diet, parturition was characterized by an increase in nonesterified fatty acid and liver triacylglycerol, as well as blood indices of inflammation (ceruloplasmin and haptoglobin), oxidative stress (reactive oxygen metabolites), and liver injury (glutamic oxaloacetic transaminase). Concentrations of the antioxidant and anti-inflammatory compounds vitamin A, vitamin E, and β-carotene decreased after calving. For vitamin A, the decrease was observed in overfed cows (47.3 vs. 27.5μg/100mL). Overall, overfeeding energy and higher energy status prepartum led to the surge of insulin and had a transient effect on metabolism postpartum.

Hormone and pharmaceutical regulation of ASP production in 3T3‐L1 adipocytes

Several studies have demonstrated increases in acylation stimulating protein (ASP), and precursor protein C3 in obesity, diabetes and dyslipidemia, however the nature of the regulation is unknown. To evaluate chronic hormonal and pharmaceutical mediated changes in ASP and potential mechanisms, 3T3-L1 adipocytes were treated with physiological concentrations of relevant hormones and drugs currently used in treatment of metabolic diseases for 48 h. Medium ASP production and C3 secretion were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride (TG) mass, non-esterified fatty acid (NEFA) release and real-time FA uptake). Chylomicrons increased ASP production (up to 411 +/- 133% P < 0.05), while leptin, triiodothyronine, and beta-blockers atenolol and propranolol had no effect. Dexamethasone, lovastatin, rosiglitazone and rimonabant decreased ASP production (-53 to -85%, P < 0.05), associated with a decrease in the precursor protein C3 (-37% to -65%, P < 0.01). By contrast, epinephrine, progesterone, testosterone, angiotensin II and metformin also decreased ASP (-54% to -100%, P < 0.05), but without change in precursor protein C3, suggesting a direct effect on convertase activity, possibly mediated by interference (except metformin) due to marked increases in NEFA (5.6-31-fold, increased P < 0.05). Both lovastatin and metformin induced decreases in ASP were also associated with decreased TG mass (maximal -60%, P < 0.05) and real-time FA uptake (maximum -75%, P < 0.05), suggesting a change in adipocyte differentiation status. These in vitro results are consistent with in vivo ASP profiles in subjects, and suggest that ASP may be regulated through precursor C3 availability, convertase activity and differentiation status.

Slimming treatment efficiency and changes in serum lipids and lipoproteins in obese adolescents.

The efficiency of a slimming treatment, which is the quantity of lean body mass (LBM) lost for each kilogram of body fat reduced, measured by Efficiency Index (EI), was investigated in nineteen obese male adolescents aged 10-14 years who lost weight during four weeks of a treatment combining hypoenergetic diet (0.18 MJ/kg of expected body weight for stature), physical exercise and psychological support. Anthropometric assessment of adiposity including body composition using Parízková and Roth's regression equations was made before onset of treatment and after 7, 14 and 28 days. Simultaneously, blood samples were drawn for serum lipids and lipoproteins. A total of seventy six observations and assessments of treatment efficiency and changes of lipid profile between every two observations were carried out. Significant correlations were found between EI values and changes in Total Cholesterol and Total Cholesterol/HDL Cholesterol ratio at the three evaluations carried out. Though HDL-Cholesterol level increase was not significant, its variations were strongly correlated with EI during the first and second assessments. Differences found in the magnitude of increase in nonesterified fatty acids (delta NEFA), suggest that lipolytic mechanisms were not uniformly impaired. Treatment efficiency and delta NEFA were lower in subjects with lesser adiposity related to muscle mass at the middle third of the upper arm (measured through Energy/Protein Index). Triglycerides and LDL + VLDL Cholesterol levels showed little variations. The achievement of a high treatment efficiency is not only necessary for preserving growth, but also for the significant decrease which occurs in some lipid fractions when EI is below 0.5.