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The objective was to investigate the effects of feed restriction on concentrations of selected milk metabolites in mid-lactation Holstein and Montbéliarde cows and to explore their correlations with energy balance and classic plasma and milk indicators of nutritional status. Eight Holstein and 10 Montbéliarde cows (165 ± 21 d in milk) underwent 6 d of feed restriction during which feed allowance was reduced to meet 50% of their net energy for lactation (NEL) requirements. The experiment was divided in 4 periods: control (CON; d −3 to −1), restriction (RES; d 1 to 6), wk 1 (W1; d 7 to 13), and wk 2 (W2; d 14 to 18) after refeeding at ad libitum intake. Intake, milk production, energy balance and plasma metabolites were used to validate the feed restriction model. Concentrations of 7 milk metabolites: β-hydroxybutyrate (BHB), glucose, glucose-6-phosphate, isocitrate, glutamate, uric acid, and free amino groups were measured in morning milk samples, and fatty acids were measured in pooled p.m. and a.m. samples. Feed restriction induced a negative energy balance (−42.5 ± 4.4 MJ/d), increased plasma nonesterified fatty acids and BHB, and decreased plasma glucose concentrations. Feed restriction increased milk glucose-6-phosphate and isocitrate (+38% and +39%, respectively) and decreased milk BHB, glucose, glutamate, uric acid and free amino group concentrations (−20%, −57%, −65%, −42%, and −14%, respectively), compared with pre- restriction. Milk concentrations of medium-chain fatty acids (e.g., sum of C10 to C15) decreased and those of long chain (e.g., 18:0, cis-9 18:1) increased during restriction. Breed differences were not detected for the majority of variables. All studied milk metabolites were significantly correlated with energy balance (Spearman correlation = 0.48, 0.63, −0.31, −0.45, and 0.61 for BHB, glucose, glucose-6-phosphate, isocitrate, and glutamate, respectively). Milk glucose and glutamate showed the strongest correlations with plasma metabolites and milk FA associated with lipomobilization. These results suggest that milk metabolites may be used as noninvasive indicators of negative energy balance and metabolic status of dairy cows.

The objective was to investigate the effects of species (cow vs. goat) and of various dietary lipid supplements, known to modulate milk fat content, on selected metabolites and enzymes in milk and to explore their correlations with performance traits. Twelve Holstein cows and 12 Alpine goats, all multiparous and nonpregnant, and at 86 ± 24.9 and 61 ± 1.8 DIM, respectively, were fed a basal diet (45% forage + 55% concentrate) not supplemented (CTL) or supplemented with corn oil plus wheat starch [COS, 5% of diet dry matter (DM)], marine algae powder (MAP, 1.5% of diet DM), or hydrogenated palm oil (HPO, 3% of diet DM) in a replicated 4 × 4 Latin square design with 28-d experimental periods. Intake, milk production and composition, milk fatty acid profile, and plasma metabolite concentrations were previously reported. Concentrations of 9 milk metabolites [β-hydroxybutyrate (BHB), glucose, glucose-6-phosphate, isocitrate, choline, glutamate, urea, cholesterol, and free amino groups] and 2 milk enzyme activities (alkaline phosphatase and lactate dehydrogenase) were measured on d 24 of each experimental period. Dairy performance data showed marked species and diet effects on milk fat content. Irrespective of diet, cow milk was richer in alkaline phosphatase and glucose compared with goat milk (16 and 3 times more, respectively), whereas goat milk had greater urea and glucose-6-phosphate concentrations compared with cow milk (1.9 and 5.3 times more, respectively). In cows, COS decreased milk BHB and choline (−25 and −43%, respectively) compared with CTL, whereas no effects were observed in goats. The COS and MAP diets increased milk isocitrate compared with CTL in cows, but COS decreased isocitrate concentrations in goat milk. Milk choline was correlated with milk fat content in cows (Spearman r, rS = +0.73) and goats (rs = +0.58), and lactate dehydrogenase activity was correlated with milk somatic cell count (rs = +0.66) in cows but not in goats. We provide evidence of different milk metabolite responses according to species and diets. Metabolites and enzymes secreted in milk may be indicators of specificities of lipid metabolism among ruminant species and may contribute to a better understanding of mechanisms regulating milk fat secretion. Changes in the concentrations of some metabolites considered minor components of milk may be valuable diagnostic tools of mammary gland and animal metabolism as well as of milk processing characteristics.

International audience; The objective of our study was to identify cow-level factors associated with subclinical hypocalcemia at calving (SCH) in multiparous Jersey cows. A total of 598 Jersey and 218 Jersey × Holstein crossbreed cows from 2 commercial dairy herds were enrolled in a retrospective cohort study. Blood samples to determine total Ca concentration were collected from the coccygeal vessels at 3 h 19 min (±2 h 33 min) after calving. We used 2 serum Ca concentration thresholds to define SCH

To produce embryos by nuclear transfer, it needs a great epigenetic reprogramming of somatic nucleus into embryonic nucleus: this reprogramming is highly dependent of oocyte capacity. Thus, each nucleus is placed in a different environment as soon as the oocyte-somatic cell fusion. This way, the cloned animals obtained using the same fibroblast line, have the same nuclear genotype, but are indubitably epigenetically different ([1]). DNA methylation, is one of the more important epigenetic modification analyzed contributes play a role in regulating gene expression and consequently in different biological processes, such as those involved in health and disease. In this study, we analyzed the genome-wide DNA methylation of a purified subpopulation of immune cells, such as monocytes from cloned and controls Holstein (n=5 per group). Born in an experimental INRA’s farm the cows were breed exactly under the same conditions limiting environmental changes. All growth, health and reproductive information has been collected. Cows were hormonally synchronized, the ovulation detected by ultrasonography and blood samples collected at D15 of cycle. Monocyte purification was performed from peripheral blood mononuclear cells obtained by Ficoll gradient, using CD14+ antibody beads. Genome-wide DNA methylation was analyzed by Reduced Representation Bisulfite Sequencing (RRBS; [2]). After sequencing, the reads were analyzed using our dedicated pipeline (https://github.com/FAANG/faang-methylation/tree/master/RRBS-toolkit). After mapping to the reference genome (UMD3.1 assembly), around of 40% of uniquely mapped reads were obtained. Only CpGs covered between 10X and 500X were analyzed and used to calculate a DNA methylation score which was not different between cloned and control groups. However, PCA described a clear separation between cloned and control groups. Differential analysis of the 10 libraries provided differentially methylated cytosine (DMCs) between the two groups, corresponding to DMRs. This study therefore highlights CpGs and regions displaying a specific methylation pattern in cloned cows.

International audience; The objective was to assess effects of experimentally induced undernutrition on responses to an intramammary lipopolysaccharide (LPS) challenge in early-lactation cows. Starting at 24 +/- 3 d in milk, multiparous Holstein cows either received a ration containing 48% straw for 96 h to restrict nutrient intake (REST, n = 8) or were allowed ad libitum intake of a lactation diet (CONT, n = 9). After 72 h on diet or after an equivalent period for CONT, 50 mu g of LPS (Escherichia coli 0111:B4) was injected into one healthy rear mammary quarter to induce an acute inflammation response. Blood samples were collected weekly until 7 wk of lactation, daily during feed restriction (or control), before and at 1, 2, 4, 6, 10, and 24 h relative to LPS injection. Foremilk quarter samples were collected before and at 4, 6, 10, and 24 h after LPS injection. Dry matter intake, milk yield, energy balance, plasma glucose, nonesterifled fatty acids (NEFA), and beta-hydroxybutyrate (BHB) concentrations did not differ between CONT and REST immediately before nutrient restriction in REST (least squares means at d -1 were 21.8, 39.0 kg/d, -2.5 MJ/d, and 3.78, 0.415, 0.66 mM, respectively) but were significantly altered at 72 h of nutrient restriction (9.8, 28.3 kg/d, -81.6 MJ/d, and 2.77, 1.672, and 2.98 mM, respectively), when the LPS challenge was performed. The rectal temperature increment from baseline values in response to LPS did not differ, but cortisol increment was greater and cortisol response area under the curve (AUC) tended to be greater [202 vs. 122 (ng/mL) x 10 h] for REST than CONT. No treatment differences were observed in foremilk IL-8, IL-1 beta, tumor necrosis factor-alpha, and chemokine (C-X-C motif) ligand 3 concentrations in response to LPS injection. Composite milk somatic cell count per milliliter (6.919 x 10(6) vs. 1.956 x 10(6) cells/mL) and total number of somatic cells secreted in milk per day were greater for REST than CONT during the day following LPS. Plasma glucose, urea, and insulin concentrations increased after the LPS challenge, suggesting establishment of insulin resistance and modifications of glucose metabolism to support acute inflammation in both CONT and REST. Nonetheless, nutrient-restricted cows had delayed plasma insulin and glucose responses to LPS, smaller insulin AUC but greater glucose AUC compared with CONT, despite the limited nutrient availability to sustain an inflammation response. Undernutrition altered peripheral metabolic responses to an intramammary LPS challenge but had limited effects on selected indicators of inflammation response in early-lactation cows.

International audience; The effects of prophylactic oral Ca supplementation on blood mineral status and markers of energy balance were evaluated on 205 multiparous Jersey cows at a commercial dairy. Postpartum, cows were systematically assigned to control (n = 105) or oral Ca supplementation (CaOS; 50 to 60 g of Ca as boluses; n = 100) at 0 and 1 d in milk (DIM). Blood samples for analysis of serum minerals (Ca, P, Mg, K, Na, Fe, Zn, and Cu) were collected before and 1 h after treatment at 0 and 1 DIM, and at 2 DIM. Urine pH was measured immediately before and 1 h after treatment administration (n = 96). A subset of 74 cows was evaluated for plasma glucose and fatty acid concentrations at 0, 1, and 2 DIM. Cows were classified according to their initial calcemic status (Ca status) as normocalcemic (NC; serum Ca > 2.12 mmol/L) or subclinically hypocalcemic (SCH; serum Ca

International audience; The aim of this study was to evaluate the effects of long-term supplementation with different oilseeds rich in 18:1 cis-9 or 18:3n-3 fatty acids on dairy cow performance over 2 consecutive lactations. This trial involved 58 Holstein cows during the first year and 35 during the second year. During the first 5 wk of the first year, all of the cows were fed the same diet; after a 4-wk transition period, the cows received 1 of 5 treatments for 2 consecutive lactations, including the dry period. Their basal diet was supplemented or not with extruded linseeds or with different forms of rapeseeds: extruded seeds, cold-pressed fat-rich meal, or whole unprocessed seeds. Oilseed amount was calculated to provide 2.5 to 3.0% additional oil in ration dry matter. Cows were fed a grass-based diet (75% grass silage and 25% hay) during indoor periods and grazed during outdoor periods. For the first year of experimentation, oilseed supplementation had no effect on milk, fat, protein, and lactose yields, body weight, or body condition score compared with the control treatment (no oilseed supplementation). During the indoor period, extruded linseed tended to decrease dry matter intake (—1.5 kg/d), whereas all of the oilseed treatments decreased milk protein content without changing protein yield. Cold-pressed fat-rich rapeseed meal decreased milk protein content independently of the period (—0.29 and ―0.19 g/100 g for indoor and outdoor periods, respectively), and whole unprocessed rapeseed increased milk fat content during the outdoor period (+0.53 g/100 g compared with the control treatment). During the second year of experimentation, the effects of oilseed supplementation during the outdoor period were similar to those observed during the first outdoor period, but the effects of oilseed supplementation differed between the 2 indoor periods. This was likely due to changes in forage quality and composition and percentage in the ration of the concentrate mixtures. Thus, the effects of oilseed supplementation depended on oilseed nature (rapeseed or linseed) and form (extruded seeds, cold-pressed fat-rich meal, or whole unprocessed seeds) in interaction with the type of basal diet (grass silage and hay or pasture) and the concentrate composition and percentage in the ration. Effects were stable during the first indoor period, repeatable between the 2 outdoor periods, and were similar to effects observed previously in short-term studies (1 to 3 mo).

International audience; The objectives were to assess the use of nicotinic acid (NA) to chronically (i.e., 74 h) manipulate plasma nonesterified fatty acid (NEFA) concentrations in partially feed-restricted lactating cows, determine whether the reduction of plasma NEFA altered responses to i.v. glucose tolerance test (ivGTT) and whether NA would attenuate an acute lipolytic stimuli of a beta-agonist challenge (ivBAC). Eight lactating dairy cows [244 +/- 31 d in milk; 696 +/- 63 kg of body weight (BW)] were blocked by breed and body condition score (3.2 +/- 0.4) and randomly assigned to a sequence of 2 treatments in a crossover design. Treatments were 74-h continuous abomasal infusion of NA solution (3 mg/h per kg of BW) as an antilipolytic agent to decrease plasma NEFA concentrations or the same volume of water (200 mL/h), concomitant with partial feed restriction. From 0 to 74 h of each experimental period, cows were feed-restricted to 33% of the ad libitum intake recorded during the prior 5 d. An ivGTT (0.25 g/kg of BW of glucose i.v.) and an ivBAC (4 nmol/kg of BW of isoproterenol hydrochloride, i.v.) were performed at 48 and 72 h, respectively. Intake was 24.1, 8.2, 8.0, and 8.0 kg of dry matter/d before restriction, on d 1, 2 and 3, respectively. Nicotinic acid decreased plasma NEFA and increased insulin and glucose concentrations during feed restriction. Nicotinic acid also led to greater glucose and insulin response areas under the curve during ivGTT [glucose: 6,562 vs. 5,056 (mg/dL) x180 min; insulin: 6,042 vs. 2,502 (mu IU/mL) x180 min] and ivBAC [glucose: 535 vs. 240 (mg/dL) x120 min; insulin: 1,283 vs. 222 (mu IU/mL) x120 min], and enhanced NEFA area under the curve during ivBAC [45,521 vs. 22,862 (mu Eq/L) x120 min]. Milk, fat, and protein yields (29.1, 1.2, and 0.93 kg on d -2, respectively) decreased to 17.9, 0.81, and 0.56 kg for control, and 11.5, 0.54, and 0.39 kg for NA on d 3, respectively. Nicotinic acid may have decreased production by inhibiting the supply of NEFA for energy and milk fat synthesis. Milk urea nitrogen was increased by NA on d 2 (12.8 vs. 19.1 mg/dL) and d 3 (11.6 vs. 17.8 mg/dL), probably due to a greater reliance on mobilized amino acids. Somatic cell count was increased by NA on d 3 (187 vs. 848 x1,000 cells/mL). Patterns of glucose and insulin concentration observed during 74 h of NA infusion reflect a state of insulin resistance, which contrasts with shorter term responses in nonlactating cows. Data suggest that long-term supraphysiological infusion of NA affected intermediary metabolism beyond antilipolysis and did not inhibit acute lipolytic stimuli of ivBAC.

International audience; During early lactation, milk fatty acid (FA) composition is influenced by diet, animal genetics, and the high availability of preformed FA from body-fat mobilization. Long-term prepartum dietary oilseed supplementation could, therefore, modify milk FA composition postpartum in the subsequent lactation through changes in adipose tissue (AT) FA profile. To test this hypothesis, measurements were made in 19 Holstein cows fed grass-based diets containing no additional lipid (control, CTL; n=4) or supplemented with extruded linseeds (EL; n=4), cold-pressed fat-rich rapeseed meal (FRM; n=6), or whole unprocessed rapeseeds (WR; n=5) over 2 consecutive lactations (yr 1 and 2) and 2 dry periods. Oilseed supplements were withdrawn from the diets 23 d before the calving of yr 3, following the end of the previous experimental periods in yr 1 to 2. Thereafter, all cows received a total mixed ration composed of grass silage, grass hay, and concentrates (forage:concentrate ratio of 70:30 on a dry-matter basis). Cows previously fed EL and WR had a lower milk fat content (6.32% for CTL and FRM vs. 5.46% for EL and WR) and yield (1.90kg/d for CTL and FRM vs. 1.61kg/d for EL and WR) during the first week of lactation. Treatment effects on milk fat content and yield did not persist into lactation wk 3 and 7. Whatever the week, EL and WR increased concentration of FA in milk synthesized de novo (i.e., carbon number ≤15; 17.1g/100g of FA for CTL and FRM vs. 22.2g/100g of FA for EL and WR) and decreased concentration and secretion of preformed FA (i.e., carbon number ≥17; 56.1g/100g of FA for CTL and FRM vs. 49.9g/100g of FA for EL and WR). Alterations in milk FA composition may be explained by the lower availability of mobilized FA for uptake by the mammary gland, as indicated by the lower plasma nonesterified FA concentrations for EL and WR compared with CTL and FRM. Prepartum EL feeding increased AT and milk concentration of 18:3n-3 (0.96 vs. 0.79g/100g of milk FA for EL and the other groups, respectively) and intermediates of ruminal 18:3n-3 biohydrogenation. In contrast, FRM increased AT and milk concentration of ruminal cis-9 18:1 biohydrogenation intermediates. However, EL and FRM supplements resulted in a similar profile of 18-carbon FA isomers in AT (yr 2) and milk (yr 3, 4-10 wk after removing oilseeds from the diet). In conclusion, results confirm that long-term feeding of oilseed supplements alter AT FA composition and may influence milk FA composition during periods of extensive body-fat mobilization such as early lactation.

International audience; The objective was to study the effects of body condition score (BCS) at calving on dairy performance, indicators of fat and protein mobilization, and metabolic and hormonal profiles during the periparturient period of Holstein-Friesian cows. Twenty-eight multiparous cows were classed according to their BCS (0 to 5 scale) before calving as low (BCS ≤2.5; n = 9), medium (2.75 ≤ BCS ≤ 3.5; n = 10), and high (BCS ≥3.75; n = 9), corresponding to a mean of 2.33, 3.13, and 4.17 points of BCS, and preceding calving intervals of 362, 433, and 640 d, respectively. Cows received the same diets based on preserved grass to allow ad libitum feed intake throughout the study, and lactation diet contained 30% of concentrate (dry-matter basis). Measurements and sampling were performed between wk −4 and 7 relative to calving. No significant effects were observed of BCS group on dry matter intake (kg/d), milk yield, BCS loss, plasma glucose, and insulin concentrations. The high-BCS group had the lowest postpartum energy balance and the greatest plasma concentrations of leptin prepartum, nonesterified fatty acids and β-hydroxybutyrate postpartum, insulin-like growth factor 1, and milk fat content. Milk fat yield was greater for the high- than the low-BCS group (1,681 vs. 1,417 g/d). Low-BCS cows had the greatest concentration of medium-chain fatty acids (e.g., sum of 10:0 to 15:0, and 16:0), and the lowest concentration and secretion of preformed fatty acids (e.g., cis-9 18:1) in milk fat. Milk protein secretion was lowest in the low-BCS group, averaging 924, 1,051, and 1,009 g/d for low-, medium-, and high-BCS groups, respectively. Plasma 3-methylhistidine was greater in wk 1 and 2 postpartum compared with other time points, indicating mobilization of muscle protein. Plasma creatinine tended to be lower and the 3-methylhistidine: creatinine ratio was greater in low- compared with medium- and high-BCS cows, suggesting less muscle mass but more intense mobilization of muscle protein in lean cows. High-BCS cows were metabolically challenged during early lactation due to intense mobilization of body fat. Conversely, limited availability of body fat in low-BCS cows was associated with increased plasma indicators of body protein mobilization during the first weeks of lactation, and lower milk protein secretion. These results should be confirmed using an experimental approach where calving BCS variation would be controlled by design.

International audience; The objective was to determine the effects of abomasal infusion of linseed oil on liver triglyceride (TG) accumulation and adipose tissue lipolysis during an experimental protocol for induction of fatty liver. Eight nonpregnant, nonlactating Holstein cows were randomly assigned to treatments in a replicated 4 x 4 Latin square design. Treatments were abomasal infusion of water (W), tallow (T), linseed oil (LO), or half linseed oil and half tallow (LOT) at a rate of 0.56 g/kg of body weight per day. Each experimental period consisted of a 4-d fast concurrent with administration of treatments into the abomasum in 6 equal doses per day (every 4 h). Cows were fed ad libitum for 24 d between periods of fasting and lipid infusion. Infusion of linseed oil (LO and LOT) increased alpha-linolenic acid (C18:3n-3) content in serum (12.2, 10.4, 4.2, and 4.6 g/100 g of fatty acids for LO, LOT, T, and W, respectively), but not in the nonesterified fatty acid (NEFA) fraction of plasma. Treatments had no effect on plasma NEFA concentrations. Abomasal infusion of lipid increased in vitro stimulated lipolysis in subcutaneous adipose tissue, compared with W (4,294, 3,809, 4,231, and 3,293 nmol of glycerol released x g(-1) tissue x 2 h(-1) for LO, LOT, T, and W, respectively), but there was no difference between fat sources. Hepatic TG accumulation over 4-d fast was 2.52, 2.60, 2.64, and 2.09 +/- 0.75 mu g of TG/mu g of DNA for W, LO, LOT, and T, respectively, which did not differ. Abomasal infusion of LO did not reduce liver TG accumulation, plasma NEFA concentration, or alter in vitro adipose tissue lipolysis when compared with T. These results contrast with a previous study involving i.v. infusion of lipid emulsion derived from LO. Discrepancies might be explained by the use of different administration routes and a relatively modest induction of liver TG accumulation in the current experiment.

International audience; The objective was to study the effects of abomasal infusion of linseed oil, a source rich in n-3 C18:3, on whole-body response to insulin (experiment 1) and on insulin antilipolytic effects during feed restriction (experiment 2). In experiment 1, eight nonlactating, non-gestating cows were assigned to a crossover design, fed to meet maintenance requirements, and infused abomasally with either linseed oil (LIN) or tallow (TAL) at a rate of 0.54 g/kg of body weight per d for 5.5 d. Infusions were performed every 8 h during the first 3 d of each period and every 4 h thereafter. Intravenous glucose tolerance tests (IVGTT) were performed on d 5 of each period, followed by i.v. insulin challenges (IC) 12 h later. In experiment 2, six nonlactating, nongestating cows were assigned to a replicated 3 x 3 Latin square design. The experimental protocol included a water (WTR) treatment and feeding was suspended on d 3, leading to 50 and 62 h of feed restriction before IVGTT and IC, respectively. Clearance of glucose during IVGTT and IC was not affected by treatments in either experiment. However, LIN had an insulin sensitizing effect in experiment 1, because a lower insulin concentration led to the same clearance of glucose as TAL. In experiment 1, plasma nonesterified fatty acid (NEFA) concentration was low, reflecting a postprandial state, but NEFA was greater for LIN than TAL during IVGTT (108 vs. 88 {+/-} 4 {micro}Eq/L) and IC (133 vs. 83 {+/-} 9 {micro}Eq/L). In experiment 2, insulin concentrations during IVGTT did not differ across treatments. Basal plasma NEFA concentration before IVGTT tended to be greater for LIN than for TAL (612 vs. 508 {micro}Eq/L). Plasma NEFA clearance rate during IVGTT was greater for LIN than for TAL (2.8 vs. 2.5%/min), leading to a shorter time to reach half NEFA concentration (25 vs. 29 min) and greater absolute value of NEFA response area under the curve [AUC; 64,150 vs. 46,402 ({micro}Eq/L) x 180 min]. Data suggest that LIN enhanced the antilipolytic effects of insulin. Yet, other factors could have been involved because plasma NEFA concentration before IVGTT was 104 {micro}Eq/L greater for LIN than TAL for unknown reasons.

International audience; The objective was to investigate the relationship between elevated plasma nonesterified fatty acid (NEFA) concentration and insulin resistance in Holstein cows. Six nonlactating, nongestating, ruminally cannulated Holstein cows were blocked by body condition score and randomly assigned to a sequence of 2 treatments in a crossover design. Cows were offered legume and grass hay ad libitum supplemented with minerals and vitamins and were allowed free access to water and a trace mineralized salt block. Mobilization of body reserves was stimulated by withdrawing forage for 48 h before initiation of treatments. Treatments consisted of 11 hourly abomasal infusions of water (control) or nicotinic acid (NA; 6 mg/h per kg of body weight) as an antilipolytic agent. Infusions of NA decreased plasma NEFA concentration from 545 {micro}Eq/L to approximately 100 {micro}Eq/L within 2 h after initiation of treatments, and differences were maintained throughout infusions. Intravenous glucose tolerance test was performed 8 h after initiation of treatments and was followed by 3 h of blood sampling. The reduction of plasma NEFA concentration led to significantly greater glucose clearance rate (1.9 vs. 1.2%/min) and to decreased glucose half-life (37 vs. 58 min), time to reach basal concentration (81 vs. 114 min) and glucose response area under the curve during 180 min of sampling [6,942 vs. 10,085 ({micro}IU/mL) x 180 min]. Enhanced glucose clearance was achieved when plasma NEFA was reduced by NA, despite lower insulin concentration (70.0 vs. 97.9 {+/-} 13.4 {micro}IU/mL) and a tendency for smaller insulin response area under the curve during 180 min of sampling [7,646 vs. 12,104 {+/-} 2,587 ({micro}IU/mL) x 180 min], reflecting an increased response to endogenous insulin. Based on literature, we do not expect NA to have altered glucose metabolism directly; therefore, this experiment demonstrates a cause and effect relationship between elevated NEFA and insulin resistance in Holstein cows.

International audience; The objective was to test whether the induction of elevated blood nonesterified fatty acids (NEFA) by i.v. infusion of a tallow emulsion altered glucose tolerance and responsiveness to insulin in Holstein cows. Six nonlactating, nongestating Holstein cows were assigned to a crossover design. One cow was excluded before initiation of the experiment because of complications from mastitis. Treatments consisted of 11-h i.v. infusions of saline ( control) or a 20% (wt/ vol) triacylglycerol ( TG) emulsion derived from tallow ( tallow) to elevate plasma NEFA. Each period consisted of two 11-h infusions (INF1 and INF2), separated by 1d in which cows were not infused. Intravenous glucose tolerance tests (IVGTT) and insulin challenges ( IC) were performed 8 h after initiation of INF1 and INF2, respectively. The infusion of treatments continued during the 3 h of sampling for IVGTT and IC. Cows were fed every 4 h at a rate to meet energy requirements for 5d prior to each period, and every 2 h during the first 8 h of infusions. Infusion of tallow induced hyperlipidemia by increasing plasma NEFA (295 +/- 9 vs. 79 +/- 7 mu Eq/ L), serum TG (41.0 +/- 6 vs. 11.4 +/- 4.4 mg/dL), and glycerol (0.81 +/- 0.09 vs. 0.23 +/- 0.1 mg/dL) concentrations during INF1. During INF2, tallow treatment increased plasma NEFA (347 vs. 139 +/- 18 mu Eq/L), serum TG (20.8 +/- 4.6 vs. 13.1 +/- 2.3 mg/dL), and glycerol (0.88 +/- 0.04 vs. 0.31 +/- 0.02 mg/dL) concentrations. Induction of hyperlipidemia impaired glucose clearance during IVGTT, despite the greater endogenous insulin response to the glucose infusion, leading to a lower insulin sensitivity index [0.29 vs. 1.88 +/- 0.31 x 10(-4) min(-1)/(mu IU/mL)]. Accordingly, hyperlipidemia impaired glucose clearance during IC (1.58 vs. 2.72 %/min), reflecting lower responsiveness to insulin. These data show that induction of hyperlipidemia causes insulin resistance in Holstein cows by impairing both sensitivity and maximum responsiveness to insulin. The induction of insulin resistance by TG, NEFA, or both may increase the availability of glucogenic nutrients to the periparturient dairy cow. Yet excessive elevation of NEFA may potentially lead adipocytes to become more insulin resistant, further increasing plasma NEFA concentration and the risk of metabolic disorders.