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Department of Dairy Science, University of Wisconsin, Madison 53706-1284
1 Corresponding author: rgrummer{at}wisc.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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Key Words: insulin resistance • hyperlipidemia • nonesterified fatty acids • bovine
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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Increased availability of plasma NEFA is mediated by changes in steroid hormones, growth hormone, insulin, glucocorticoids, and catecholamines, and by changes in the response of target tissues to these hormones (Bell and Bauman, 1997). Late gestation is characterized by a gradual decline in insulin concentration (Doepel et al., 2002) and establishment of insulin resistance (IR) in peripheral tissues, which is partially due to enhanced growth hormone concentrations (Bell and Bauman, 1997). In dairy cows, the clearance of glucose during i.v. glucose tolerance test (IVGTT) was impaired at 3 wk postpartum when compared with 3 wk prepartum (Holtenius et al., 2003). Nevertheless, the insulin response to infusion of glucose was smaller postpartum than prepartum. Therefore, the reduced clearance of glucose observed postpartum may have been due to the smaller insulin concentrations during IVGTT, to development of IR, or, most probably, to a combination of both factors.
The onset of IR will promote sparing of glucose, increased lipolysis in adipose tissue, and increased availability of NEFA for oxidation and milk fat synthesis. Plasma NEFA gradually increase during the last 2 wk of gestation and peak at calving (Grummer, 1993; Vazquez-Añon et al., 1994). During late gestation, especially during the last week of pregnancy, intake declines, leading to negative energy balance at calving (Doepel et al., 2002) and promoting further mobilization of body reserves. Modest increases in plasma NEFA concentration can occur before initiation of DMI depression (Vazquez-Añon et al., 1994; Holtenius et al., 2003), indicating possible hormonal regulation in the onset of adipose tissue mobilization independent of depression of feed intake. Negative energy balance continues through the first weeks of lactation because of the steady increase in milk production after calving and the slower rate of increase in feed intake (Doepel et al., 2002).
Excessive elevation of NEFA concentrations is associated with decreased feed intake and the onset of metabolic disorders (Grummer, 1993). Both short- and long-term elevation of plasma NEFA concentrations causes IR in the muscle and liver of nonruminants because the metabolism of NEFA and triacylglycerol (TG) increases the intracellular availability of long-chain acyl-coenzyme A and diacylglycerol, and these metabolites interfere with the intracellular insulin receptor signaling cascade (Lewis et al., 2002). Furthermore, the ability of insulin to inhibit hormone-sensitive lipase and suppress NEFA release from adipose may be impaired in IR states (Lewis et al., 2002), and in vitro treatment of adipocytes with fatty acids affects their response to insulin. A 4-h incubation of adipocytes (3T3-L1 cell line) with only 300 µEq/L of palmitate is sufficient to induce IR (Van Epps-Fung et al., 1997). This concentration of palmitate is within the lower physiological range of NEFA observed in periparturient dairy cows, when NEFA may increase to more than 1,000 µEq/L. Accordingly, the incubation of the same cell line with 300 µEq/L of linoleic acid induced IR by influencing key intracellular steps in the insulin signaling cascade, as observed in other tissues (Gao et al., 2004).
The establishment of NEFA-induced IR in adipose tissue of periparturient dairy cows could lead to the onset of a vicious cycle in which a higher NEFA concentration would promote greater mobilization of body reserves, potentially leading to the onset of metabolic disorders. Nonesterified fatty acid-induced IR could partially explain the well-established negative association between excessive BCS at calving and energy-related metabolic disorders. For instance, cows that were overfed prepartum and calved overconditioned (BCS >4) had sustained elevated plasma NEFA during the first 4 wk of lactation and presented impaired clearance of glucose, despite a greater insulin response to i.v. glucose infusion (Holtenius et al., 2003). These results clearly show an association between excess body condition, elevated NEFA, and IR.
To our knowledge, the effects of elevated NEFA concentration on the establishment of IR in dairy cows have not been addressed experimentally. We hypothesized that an elevated concentration of NEFA causes whole-body IR in Holstein cows, and it was our objective to test whether the induction of elevated blood NEFA, by i.v. infusion of a TG emulsion, would induce IR in Holstein cows.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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Animals and Treatments
Six nonlactating, nongestating, ruminally cannulated Holstein cows were randomly assigned to treatments in a crossover design with 2 periods. One cow was excluded before initiation of the first period because of complications from mastitis; thus, data presented are derived from 5 animals.
Cows were weighed on 2 consecutive days (722 ± 46 kg of BW; mean ± SD) the week before initiation of treatments, and BCS (Wildman et al., 1982) was recorded (3.2 ± 0.20; mean ± SD). Body weight was used to determine the doses of feed, treatments, glucose for IVGTT, and insulin for IC.
One day prior to initiation of treatments, sterile and nonpyrogenic catheters were inserted into the right (14-gauge x 14-cm, Abbocath-TAL catheter; Abbott Laboratories, North Chicago, IL) and left (18 cm x 1.78 mm o.d. Tygon microbore tubing; Fisher Scientific Co., Pittsburgh, PA) jugular veins. Patency was maintained by flushing catheters with 5 mL of heparinized saline (100 IU/mL) every 8 h or with diluted heparinized saline (10 IU/mL) during frequent sampling. Cows were given 10,000 IU/d per kg of BW of penicillin G (G.C. Hanford Mfg. Co., Syracuse, NY) following the insertion of catheters as a prophylactic procedure.
Treatments consisted of 11-h i.v. infusions of either saline (control treatment) or a 20% TG emulsion derived from tallow (tallow treatment), used to elevate plasma NEFA. With this design, each cow received either saline or the tallow emulsion in each period. Tallow was chosen as the TG source to mirror the fatty acid composition of ruminant fat depots. Treatments were administered continuously via drip infusion at a targeted rate of 0.1 g of TG/kg of BW per h for tallow and the same volume (0.5 mL/kg of BW per h) for the control. Each period consisted of two 11-h infusions of treatments (INF1 and INF2) separated by 1 d in which cows were not infused. Blood samples were collected immediately before initiation of treatments and every 2 h during the first 8 h of infusion of treatments. The Animal Care and Use Committee for the College of Agriculture and Life Sciences at the University of Wisconsin-Madison approved all animal procedures.
IVGTT and Insulin Challenges
During INF1 of each period, 8 h after the initiation of treatments, IVGTT were performed by administering 0.25 g/kg of BW of glucose i.v. (dextrose 50% wt/vol; Phoenix Scientific Inc., St. Joseph, MO) over 4.5 ± 1.1 min (mean ± SD).
During INF2, 8 h after the initiation of treatments, insulin challenges (IC) were performed by administering 0.1 IU/kg of BW of insulin i.v. (100 IU/mL; Humulin R, human insulin rDNA origin; Eli Lilly Co., Indianapolis, IN) over 1.0 ± 0.1 min (mean ± SD) followed by 20 mL of saline.
Blood samples were collected at –30, –15, –5, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, and 180 min relative to administration of glucose or insulin. Samples collected at 5 min were used only for IC.
The infusion of treatments continued during the sampling periods of IVGTT and IC (3 h). All blood samples were collected from the left jugular vein, whereas the infusion of treatments, administration of glucose for the IVGTT, and insulin for the IC were made into the right jugular vein. A catheter with a larger diameter was used in the right jugular vein to facilitate the flow of treatments and glucose for the IVGTT.
Diets and Feeding
Cows were fed at a rate to meet maintenance requirements (NRC, 2001). Feed was provided once daily between periods, every 4 h starting 5 d prior to initiation of treatments, and every 2 h during the first 8 h of treatment (tallow or control) infusions. The meal preceding IVGTT and IC was provided 2 h before the infusion of glucose or insulin to reduce potential interferences in the blood metabolite clearance patterns. Feeding was suspended during IVGTT and IC sampling.
The diet was composed of 37% alfalfa silage, 31% corn silage, 21% wheat straw, and 11% wheat middlings as the carrier for vitamins and minerals (DM basis). The diet was formulated to have 49% NDF, 33% ADF, 15.3% CP, and 1.44 Mcal/kg of DM of NEL, based on near-infrared reflectance spectroscopy from alfalfa silage and corn silage (UW Soil and Forage Feed Analysis Laboratory, Marshfield, WI) and tabular values (NRC, 2001) for the remaining diet components.
Estrus Synchronization
Cows were synchronized with an intravaginal progesterone-releasing device (CIDR containing 1.38 g of progesterone; Eazi-Breed, Hamilton, NZ) for 7 d. On the day before INF1, the device was removed and all follicles with diameter >5 mm were aspirated with an ultrasound-guided transvaginal approach, using a 17-gauge x 55 cm needle and 7.5-MHz convex array transducer (Aloka SSD-900V; Aloka Co., Wallingford, CT). Follicular aspirations were performed twice each period; the day before INF1 and the day before INF2. Prostaglandin F2
(Lutalyse, 25 mg; Pfizer Animal Health, Kalamazoo, MI) was administered i.m. 36 and 24 h before CIDR withdrawal to induce luteolysis. These procedures were performed to keep circulating progesterone and estradiol low in each experimental period and reduce potential interference with IVGTT and IC (Livingstone and Collison, 2002).
Blood Plasma and Serum Analysis
Blood was obtained from catheters using disposable 20-mL syringes and then transferred to Vacutainer tubes (Becton Dickinson, Franklin Lakes, NJ) for the separation of plasma (tubes contained 12 mg of potassium oxalate and 15 mg of sodium fluoride as a glycolytic inhibitor) and serum (additive-free tubes). Tubes for collection of blood plasma were kept on ice until centrifugation at 920 x g at 4°C, for 20 min. Tubes for collection of serum were allowed to clot at room temperature and were centrifuged at 2,050 x g at 20°C, for 20 min.
Plasma samples were analyzed for glucose (glucose oxidase/peroxidase method; Karkalas, 1985) and NEFA (NEFA-C kit; Wako Chemical USA, Richmond, VA; Johnson and Peters, 1993). Serum samples were analyzed for glycerol and TG (TR0100; Sigma Chemical Co.; McGowan et al., 1983), and insulin (porcine insulin RIA kit PI-12K; Linco Research Inc., St. Charles, MO). Intra- and interassay coefficients of variation were 2.8 and 2.8% for glucose, 3.5 and 6.3% for NEFA, 3.9 and 6.1% for glycerol, 4.4 and 11.3% for TG, and 5.0 and 11.4% for insulin.
Serum samples collected 30 min before IVGTT and IC were analyzed for estradiol and progesterone. Serum was extracted twice with diethyl ether and concentrations of E2 were measured using a commercial RIA kit for estradiol (Third Generation Estradiol Assay kit; Diagnostics System Laboratories Inc., Webster, TX) previously validated for use in cattle (Kulick et al., 1999). Circulating progesterone was evaluated from un-extracted serum using an antibody-coated-tube RIA kit (Coat-A-Count Progesterone; Diagnostic Products Corporation, Los Angeles, CA) validated by Lopez et al. (2004). The intraassay coefficients of variation for estradiol and progesterone were 9.5 and 6.2%, respectively.
Calculations and Statistical Analysis
Statistical analysis was performed using SAS version 9.1 (SAS Institute, 2004). The PROC NLIN was used to fit exponential curves for glucose concentration during the first 60 min of IVGTT, and for insulin and glucose concentrations during the first 30 min of IC (Hayirli et al., 2001) using the following equation:
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where F(t) is the metabolite concentration at time t; A is the maximum value of glucose (estimated for IVGTT; basal glucose concentration for IC), or estimated maximum insulin concentration (during IC); t is the time (min); and k is the regression coefficient. The following parameters were calculated:
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where [ta] is the concentration of metabolite at time a (ta), and [tb] is the concentration of metabolite at time b (tb).
The areas under the curve (AUC) of glucose and insulin during IVGTT and IC were calculated using the trapezoidal method and actual concentration values, after discounting the baseline concentration. Basal glucose and insulin concentrations (immediately before IVGTT and IC) were calculated by averaging values from samples taken 15 and 5 min prior to IVGTT or IC.
The insulin sensitivity index was obtained by analyzing the glucose and insulin concentrations for each animal using the Minimal model for IVGTT (Bergman, 1997). In this model, insulin-stimulated glucose disappearance reflects both the inhibition of production and increased uptake of glucose by peripheral tissues.
The parameters obtained from IVGTT, IC, and the Minimal model were analyzed using PROC MIXED of SAS. The model included the fixed effects of treatment and sequence, and the random effects of period and cow within sequence. A covariate was used to adjust for differences in glucose concentration before the challenges. This covariate was removed when its significance level was greater than 0.20.
The concentration of metabolites was analyzed using repeated measures in time (Littell et al., 1998) with a spatial power covariance structure to allow for unequal spacing between sampling times, and adding treatment, time, and a treatment x time interaction to the model. Heterogeneous variance across treatments was used when providing the best fit according to the Schwarz’s Bayesian criterion. In models used to study glucose and insulin concentrations after the IVGTT and IC, a covariate was used to adjust for differences in concentration before the challenges. This covariate was removed when the significance level was greater than 0.20.
The significance level for treatment effects was predefined at P < 0.10 and trends toward significance at 0.10 
P < 0.15 for the IVGTT and IC parameters. For repeated measures, the significance level for treatment, time, and a treatment x time interaction was reduced to P < 0.05 to decrease the risk of type I error. If the treatment effect or the treatment x time interaction was significant, the SLICE option was used to compare treatment differences at individual time points. Values reported are least squares means and standard errors of the mean unless otherwise stated.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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), which represents an increase of more than 3.7-fold.
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) and glycerol (P < 0.001) concentrations, and a treatment x time interaction (P < 0.001) for both TG and glycerol. Triacylglycerol concentrations increased throughout the 11 h of infusion with tallow, starting at 9.7 mg/dL immediately before initiation of treatment and ending at 68.4 mg/dL by h 11 of the infusion, with an overall mean of 41.0 ± 6 mg/dL. Triacylglycerol averaged 11.4 ± 4.4 mg/dL for the control. Glycerol increased with tallow, reaching a plateau during the first 2 h of treatment infusion. Glycerol was 0.81 ± 0.09 and 0.23 ± 0.1 mg/dL for the tallow and control infusion, respectively.
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Serum insulin increased from 20.0 µIU/mL before initiation of the treatment infusion to 68.5 µIU/mL 8 h after initiation of the tallow infusion. Insulin was 49.2 ± 5.2 µIU/mL for tallow and 22.2 ± 2.4 µIU/mL for the control.
Glucose and Insulin During IVGTT.
Glucose concentration was higher immediately before IVGTT when cows received tallow (76.2 vs. 66.2 ± 2.5; P < 0.05). Glucose clearance was impaired by tallow, leading to a lower CR, and longer times to reach half maximal glucose concentration and to reach basal levels (Figure 3; Table 1).
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). Accordingly, AUC for the insulin concentration was greater for tallow than for the control during the first 60 min of sampling (P < 0.10), 14,581 vs. 7,271 ± 1,957 [(µIU/mL) x 60 min], and throughout the 180 min of sampling of IVGTT (P = 0.05), 19,719 vs. 7,672 ± 2,706 [(µIU/mL) x 180 min].
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), and there was a treatment x time interaction (P < 0.001).
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) and there was a treatment x time interaction (P < 0.05). Triacylglycerol reached a plateau at approximately 4 h after initiation of INF2. This contrasted with INF1, during which TG increased continuously throughout the 11 h of tallow infusion. Serum TG was 20.8 ± 4.6 and 13.1 ± 2.3 mg/dL for the tallow and control infusion, respectively. Serum glycerol concentration was higher for cows receiving tallow than those receiving the control, reaching a plateau during the first 2 h of treatment infusion. Glycerol was 0.88 ± 0.04 and 0.31 ± 0.02 mg/dL for the tallow and control infusion, respectively, and there was a treatment x time interaction (P < 0.001).
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Glucose and Insulin During IC.
The treatment effects on glucose concentration during IC are shown in Figure 7. Infusion of tallow impaired glucose clearance (P = 0.06), decreasing the absolute value of the glucose response AUC during the first 30 min of IC (P = 0.04) and increasing the time needed to reach half the glucose concentration (P = 0.02; Table 2).
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). Insulin CR30 was 4.2 vs. 4.3 ± 0.64 %/min; T1/2 was 18 vs. 17 ± 2.8 min; Tbasal was 98 vs. 112 ± 18.8 min; AUC during the first 30 min of IC was 14,524 vs. 15,565 ± 1,589 (µIU/mL) x 30 min; AUC during the 180 min of IC was 16,206 vs. 17,966 ± 2,270 (µIU/mL) x 180 min for the tallow and control infusion, respectively.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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Cows were rumen cannulated to allow the eventual manual delivery of feed refusals into the rumen and maintain feed intake during the first 8 h of treatment infusions. Nevertheless, cows consumed the feed within minutes after each of the 4 meals was provided during INF1 and INF2 (every 2 h, before IVGTT and IC).
In this experiment, infusion of tallow caused an increase in blood NEFA, TG, and glycerol concentrations throughout INF1 and INF2. Therefore, we cannot say that elevation of NEFA per se caused the treatment effects, but rather that they resulted from hyperlipidemia. The degree of variation in the concentration of TG in periparturient dairy cows is extremely modest when compared with the increases in plasma NEFA (Guretzky et al., 2006). Therefore, the increase in serum TG concentration by tallow may potentially result in a different physiological state from that of the periparturient cow. Yet serum TG may affect the cellular responses to insulin through a mechanism similar to circulating NEFA, because TG originating from i.v. emulsion enters the cells of peripheral tissues mostly as NEFA and monoacylglycerol (Ferezou and Bach, 1999).
Tallow successfully promoted sustained increases in plasma NEFA concentrations throughout INF1 and INF2 (Figures 1
and 5). The concentrations of NEFA achieved during the treatment infusions were within the range found when lactating cows were infused for 4 h with a commercial soybean oil-based emulsion at a rate of approximately 0.15 g/kg of BW per h, which caused an increase in NEFA of 224 µEq/L (Bareille and Faverdin, 1996). But plasma NEFA have risen to more than 1,200 µEq/L when lactating cows were infused with a soybean oil-based emulsion for 6 h at a rate close to the one used in our experiment (approximately 0.1 g of TG/kg of BW per h; Chelikani et al., 2003). The reason for the differences in NEFA concentrations across these experiments is not known.
Intravenous glucose tolerance tests and IC were performed 8 h after initiation of INF1 and INF2, respectively, and caused an initial decrease of NEFA for both the tallow and the control infusion, followed by a rebound (Figures 1 and 5). A decrease in NEFA concentration is commonly observed after the IVGTT (Lemosquet et al., 1997; Hayirli et al., 2001), and it is caused by pancreatic secretion of insulin in response to i.v. administration of glucose (Figure 4), leading to a reduction of NEFA output from adipose. The subsequent rebound in NEFA concentration probably results from the gradual decline in insulin concentrations. The perturbation in the NEFA concentration pattern was more pronounced during INF2, after i.v. infusion of the insulin bolus for the IC (Figure 5). The dose of insulin used in the IC led to a transient supra-physiological concentration of insulin, followed by a rapid decline (Figure 8). The subsequent rebound of NEFA was particularly sharp when cows received the control infusion (Figure 5), probably as a result of a more marked hypoglycemia (Figure 7).
Previous reports indicate that serum TG concentrations in dairy cows range from 6 to 33 mg/dL (Lemosquet et al., 1997; Guretzky et al., 2006). In our experiment, serum TG was within that range except during INF1, which was characterized by a continuous increase of serum TG throughout the 11 h of infusion with tallow (Figure 2). This accumulation of TG in serum may have been due to the saturation of lipoprotein lipase.
Serum TG accumulation was less dramatic with INF2 of tallow (Figure 6) than during INF1 for the same treatment (Figure 2), possibly because of up-regulation of TG-clearing mechanisms caused by the previous exposure to emulsion during INF1, which occurred 48 h earlier. In agreement with the results from INF2, plasma total TG was elevated from 6.1 to only 16.5 when cows were infused i.v. with a commercial soybean oil-based emulsion for 4 h, at a rate of approximately 0.15 g/kg of BW per h (Bareille and Faverdin, 1996).
Experimental protocols for the study of interrelationships between elevated plasma NEFA and IR in nonruminants frequently involve infusion of a lipid emulsion and heparin. Heparin stimulates lipoprotein lipase translocation to the capillary endothelium and its release to the bloodstream promotes lipolysis, increases plasma NEFA, and accelerates clearance of emulsion TG (Chen et al., 1995). Previous work from our group suggested that heparin exerts only transient stimulatory lipolytic effects in the bovine (Mashek et al., 2005); therefore, we did not infuse heparin with the emulsion in this experiment. Nevertheless, considering the high infusion rate used in our protocol and the duration of treatments, it might have been useful to provide heparin concomitantly with tallow to stimulate TG hydrolysis by lipoprotein lipase (Chen et al., 1995), especially during INF1.
The increased glycerol concentration observed with tallow during INF1 and INF2 was expected and probably resulted directly from the emulsion (2.5% wt/vol glycerol) and from the lipolysis of emulsion TG. Despite being a gluconeogenic precursor, we do not expect this increase to have influenced the results. The average cow in this experiment weighed 722 kg and received approximately 99.3 g of glycerol as an ingredient of the emulsion plus 79.4 g as part of the TG backbone, assuming that TG contains 10% wt/wt glycerol and that all TG was completely hydrolyzed. This corresponds to a maximum of 16.2 g/h of glycerol, or 0.375 mg/kg of BW per h. The infusion of glycerol at approximately 1.9 times this rate (0.7 mg/kg per h glycerol, plus 0.4 IU/kg per min of heparin) did not alter glucose utilization or endogenous glucose production in humans (Boden et al., 1994). Furthermore, glycerol was found in low concentrations in our experiment (less than 1 mg/dL for tallow). Therefore, we suggest that the treatment effects observed with tallow were mainly due to the fatty acids originating from the hydrolysis of emulsion TG.
Throughout this experiment, during the first 8 h of INF1 and INF2, and during IVGTT and IC, glucose and insulin concentrations followed a pattern that was consistent with the induction of IR by tallow. During the first 8 h of INF1, glucose and insulin concentrations were greater when cows received tallow; the higher concentration of insulin was insufficient to lower the glucose concentration. During the first 8 h of INF2, a higher concentration of insulin was needed to achieve the same glucose concentration for tallow as for the control. These results reflect a situation of IR induced by tallow during INF1 and INF2.
Hyperlipidemia affected the clearance of glucose during IVGTT (Figure 3, Table 1), despite a greater insulin response observed with tallow (Figure 4). The plasma glucose concentration during IVGTT depends on glucose utilization by peripheral tissues, endogenous glucose production, absorption of glucose from the intestine, and excretion of glucose by the kidney. Nonlactating, nongestating cows should have relatively low gluconeogenic rates, because their glucose utilization is low when compared with gestating or lactating cows (Bell and Bauman, 1997). The increase in insulin concentration during IVGTT should have been sufficient to inhibit hepatic glucose production, because insulin at physiologic concentrations inhibits gluconeogenesis and hepatic glucose output in the ruminant (Brockman and Laarveld, 1986). We expect that negligible amounts of glucose were absorbed from the intestine, with no differences in the uptake of gluconeogenic precursors between treatments because cows were fed a forage-based diet at a rate to meet maintenance requirements. To our knowledge, there are no data suggesting a possible effect of treatments on excretion of glucose by the kidney. Therefore, decreased clearance of glucose during IVGTT with infusion of tallow was most probably due to decreased utilization of glucose by peripheral tissues. Lower clearance of glucose during IVGTT despite greater concentrations of insulin reflected a situation of IR induced by hyperlipidemia.
Increased insulin concentration during IVGTT when cows received tallow probably resulted from increased pancreatic secretion and not from decreased clearance of insulin, because the clearance of exogenous insulin after IC was not affected by hyperlipidemia (Figure 8). This shows that short-term hyperlipidemia does not affect whole-body insulin clearance in Holstein cows.
The insulin sensitivity index was reduced when cows received tallow, as compared with the control (0.29 vs. 1.88 ± 0.31 x 10–4 min–1/(µIU/mL); P < 0.05), which is in agreement with the higher concentrations of glucose and insulin observed during IVGTT for tallow. These values mean that for each 10-unit increase in serum insulin concentration, there was an increase of 0.188 %/min in fractional glucose disappearance with the control infusion, and only 0.029 %/min with tallow. The induction of hyperlipidemia reduced the insulin sensitivity index to only 15.4% of the control value.
Hyperlipidemia influenced the clearance of glucose during IC (Figure 7; Table 2), which is in agreement with the results from IVGTT. Insulin challenge caused a transient supra-physiological increase in insulin (Figure 8). Clearance of glucose during IC can be interpreted as the maximal response to insulin, and our results showed that insulin responsiveness was impaired by hyperlipidemia.
In summary, the induction of hyperlipidemia impaired insulin sensitivity and insulin responsiveness in Holstein cows. The impact of IR on the metabolic status and productivity of the dairy cow will ultimately depend on the degree of IR and on which tissues become insulin resistant. The potential effects of elevated NEFA concentrations on IR in periparturient dairy cows have not been addressed experimentally. Our results suggest that an elevated NEFA concentration during the periparturient period may be a key factor triggering IR in Holstein cows. Nonetheless, further experimentation is needed to confirm this, because blood metabolites other than NEFA were elevated during i.v. administration of the lipid emulsion.
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CONCLUSIONS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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ACKNOWLEDGEMENTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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Received for publication November 14, 2006. Accepted for publication January 24, 2007.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGEMENTSREFERENCES |
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—) or a tallow emulsion (—
—) on plasma NEFA concentration during the first infusion of treatments of each period. Intravenous glucose tolerance tests were performed 8 h after initiation of treatments. Fixed effects in the statistical model: sequence (NS), treatment, time (P < 0.001), and treatment x time (P < 0.001). *Treatments differed at each time point (P < 0.001). Error bars are SEM.
