Lower Nonesterified Fatty Acid Concentrations Research Articles

Leptin Concentration, Obesity, and Plasma Non-esterified Fatty Acid Levels in Children.

The association between obesity and higher non-esterified fatty acid (NEFA) levels has been established in adults. In contrast, lower NEFA levels have been described in children with obesity although the reason behind this association remains unclear. Leptin, which regulates body weight and plays a role in lipolysis, could be involved in this relationship. We evaluated the influence of leptin in the association between obesity and NEFA concentrations in children, analyzing two cohorts including 684 6- to 8-year-olds and 836 12- to 16-year-old children, respectively. After adjusting by leptin, insulin levels remained significantly higher in adolescents with obesity as compared with levels in those without obesity. However, insulin levels showed no differences between prepubertal children with and without obesity. The significantly lower NEFA concentrations observed in 6- to 8-year-old girls with obesity disappeared when comparing NEFA levels between girls with and without obesity after adjusting by leptin. We report an influence of leptin levels on the association between obesity and insulin and NEFA in young children that is not observed in adolescents. Our findings add information about factors that may contribute to explain the lower NEFA levels described in prepubertal children with obesity.

Provision of shelter during the prepartum period: Effects on behavior, blood analytes, and health status in dairy cows in winter

This study aimed to assess the effect of shelter provision during the prepartum period on lying, ruminating, and feeding behavior in outdoor-housed dairy cows exposed to winter weather conditions in a temperate climate. We also aimed to determine whether shelter provision during the prepartum period influenced blood analytes related to energy metabolism, body cleanliness, and health status. In this study, 2 cohorts of 12 multiparous Holstein prepartum cows were tested in winter. Twenty-five days before their expected calving date, the cows in each cohort were paired and randomly assigned to an open paddock without shelter or to one with access to an artificial shelter until calving. Shelter use, lying time, number of lying bouts, duration of lying bouts, rumination time, and feeding time were continuously recorded during the 3 wk before calving. Cows were assessed weekly for body cleanliness throughout the 3-wk prepartum period. A blood sample was taken from the coccygeal vein of each cow at wk -3, -2, -1, 1, 2, and 3 relative to calving date, and were assayed for nonesterified fatty acids (NEFA), β-hydroxybutyrate, and haptoglobin concentrations. Cases of clinical health disorders after calving were also recorded. The cows spent 60% of their daily time in the shelters, and for 75% of that time they were lying down. Cows with access to shelter during the prepartum period lay down around 3.2 h/d more than cows without shelter on wk -3 and -2 relative to calving. The cows with shelter access spent less time feeding during the morning (wk -3: 29.7 min; wk -2: 12.1 min; wk -1: 17.3 min) and afternoon (wk -3: 18.2 min; wk -2: 21.9 min) than cows without shelter access. As well, cows with shelter access showed a higher body cleanliness score (∼92 vs. ∼48%) and lower NEFA concentrations (wk -2: 0.27 vs. 0.44 mmol/L; wk -1: 0.46 vs. 0.64 mmol/L) in the precalving period, and lower haptoglobin concentrations in the first week postpartum (0.34 vs. 0.79 mg/mL) than cows without shelter access. We observed no treatment differences in daily rumination time, β-hydroxybutyrate concentrations, or postpartum health disorders. Despite the small number of dairy cows used in this study, these findings suggest that having access to a shelter during the prepartum period increases lying time, improves body cleanliness, and reduces adipose mobilization. Therefore, it is important to provide a protected area for the welfare of prepartum dairy cows exposed to winter climate conditions.

Relationships between body condition, body condition loss, and serum metabolites during the transition period in primiparous and multiparous cows

In the transition period from late gestation to early lactation, dairy cows undergo tremendous metabolic changes. Insulin is a relevant antilipolytic factor. Decreasing serum concentrations of insulin and glucose, increasing serum concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHB), and changes in body condition score (BCS) reflect the negative energy balance around calving. This study investigated peripartum metabolic adaptation in 359 primiparous and 235 multiparous German Holstein cows from a commercial dairy herd under field conditions. Body condition score was recorded and blood samples were taken 10 to 1 d prepartum, 2 to 4 d postpartum, and 12 to 20 d postpartum. Generalized mixed models and generalized estimation equations were applied to assess associations between prepartum BCS; BCS changes during the transition period; insulin, glucose, NEFA, and BHB serum concentrations; and milk yield, which was taken from an electronic milk meter from d 6 of lactation. Serum insulin concentrations of multiparous postpartum cows were lower compared with prepartum, and compared with primiparous cows. In general, primiparous cows had lower postpartum NEFA and BHB concentrations than multiparous cows. In primiparous cows, we identified a positive association between prepartum BCS and prepartum serum insulin concentration. Prepartum obese multiparous cows, but not primiparous cows, were characterized by higher postpartum serum NEFA and BHB concentrations and lower milk yield than other cows in the same parity class. Primiparous cows with a smaller degree of BCS loss during the transition period had higher postpartum insulin and lower NEFA concentrations and lower milk yield than other primiparous cows. In conclusion, primiparous cows had less lipolysis and lower milk yield than multiparous cows, associated with higher insulin concentrations. Avoiding high body condition loss during the transition period is a main factor in preventing peripartal metabolic imbalances of glucose and fat metabolism.

Dietary Inclusion of 1,3-Butanediol Increases Dam Circulating Ketones and Increases Progeny Birth Weight.

1,3-Butanediol (BD) is a ketogenic substance that can improve piglet growth and survival and potentially increase performance in gilt progeny when provided as a dietary supplement during late gestation. Gilts (n = 77; parity 1) and sows (n = 74; parities 2 and 3) were fed either a standard commercial gestation diet or a diet supplemented with 4% BD from day 90 of gestation until farrowing. Dams fed with diets supplemented with BD had higher plasma beta-hydroxybutyrate (p = 0.01) and lower non-esterified fatty acid concentrations (p < 0.001). The percentage of progeny that were light-for-age (<1.1 kg) at birth was decreased by BD (18.2 vs. 13.5%, p < 0.006), particularly in gilts (24.0 vs. 18.3%, p < 0.034). Individual birth weights and litter weights birth weights tended to be increased by the BD diet (p = 0.085 and 0.078; respectively) although these effects were not maintained to weaning. Pre-weaning mortality was greater in gilt than in sow progeny and was not altered by dietary BD. Feeding BD in late gestation can improve birth weight, but further work is needed to see if these effects are carried through subsequent stages of growth, particularly in gilt progeny.

Energy balance in transition cows and its association with health, reproduction and milk production.

It was the purpose of this study to determine the effects of non-esterified fatty acids (NEFA) concentrations at different time periods of the transition period as well as lactation number on metabolism, health, reproduction and milk production in dairy cows. This trial was conducted in a single dairy herd located in Northern Germany. Of the herd, which comprised 330 lactating Holstein cows housed in a free stall barn and fed a total mixed ration (TMR), 83 primiparous and multiparous cows were randomly selected. Animals were checked for body condition score (BCS), locomotion score, calving data, quality of colostrum, reproductive measures, daily rectal temperature of the first 10days post-partum (p.p.), health data and culling rates up to 200days in milk (DIM) as well as milk production until 305DIM. Three different time periods were considered: 3 and 1week ante partum (a.p.); partus and 1weekp.p.; 3weeksp.p. Animals with NEFA concentrations ≥0.4mmol/l ante partum had a higher risk of no ovarian activity in week 5p.p. and of subclinical ketosis post partum than cows with lower NEFA concentrations (p<0.05). Cows with NEFA concentrations ≥1.1mmol/l in week 1p.p., in comparison to those with lower NEFA concentrations, showed a higher prevalence of clinical ketosis (24.1% vs. 5.9%), subclinical ketosis (62.1% vs. 34.0%) and culling rate within 200DIM (34.5% vs. 14.0%) (p < 0.05). Cows with NEFA concentrations ≥0.3mmol/l at week 3p.p. had higher 100- and 305-day milk yields than cows with lower NEFA concentrations (p<0.05). First lactating heifers were at higher risk to loose body condition ante partum, of dystocia, fever within the first 10DIM, metritis, clinical and subclinical ketosis as well as to develop a disease within the first 30DIM (p<0.05). Multipara were more likely to loose body condition after calving, to a prolonged calving to first service interval and to higher milk yields (p<0.05). In conclusion increased NEFA concentrations during the transition period as well as parity can have an influence on health, production and reproduction of dairy cows.

Prepartum nutritional strategy affects reproductive performance in dairy cows

Negative energy balance during early postpartum is associated with reduced reproductive performance in dairy cows. A pooled statistical analysis of 7 studies completed in our group from 1993 to 2010 was conducted to investigate the association between prepartum energy feeding regimen and reproductive performance. The interval from calving to pregnancy (days to pregnancy, DTP) was the dependent variable to assess reproductive performance. Individual data for 408 cows (354 multiparous and 54 primiparous) were included in the analysis. The net energy for lactation (NEL) intake was determined from each cow’s average dry matter intake and calculated dietary NEL density. Treatments applied prepartum were classified as either controlled-energy (CE; limited NEL intake to ≤100% of requirement) or high-energy (HE; cows were allowed to consume >100%) diets fed during the far-off (FO) or close-up (CU) dry periods. Cow was the experimental unit. The Cox proportional hazard model revealed that days to pregnancy was shorter for CE (median=157d) than HE (median=167d) diets during the CU period [hazard ratio (HR)=0.70]. Cows fed HE diets during the last 4wk prepartum lost more body condition score in the first 6wk postpartum than those fed CE diets (−0.43 and −0.30, respectively). Cows fed CE diets during the FO period had lower nonesterified fatty acids concentrations in wk 1, 2, and 3 of lactation than cows fed HE diets. Higher nonesterified fatty acids concentration in wk 1 postpartum was associated with a greater probability of disease (n=251; odds ratio=1.18). Cows on the CE regimen during the FO period had greater plasma glucose concentrations during wk 1 and 3 after calving than cows fed the HE regimen. Higher plasma glucose (HG) concentration compared with lower glucose (LG) in wk 3 (HG: n=154; LG: n=206) and wk 4 (HG: n=71; LG: n=254) after calving was associated with shorter days to pregnancy (wk 3: median=151 and 171d for HG and LG, respectively, and HR=1.3; wk 4: median=148 and 167d, respectively, and HR=1.4). In the first 2wk after calving, cows that received HE diets in the FO period had higher concentrations of total lipids and triglyceride and greater ratio of triglyceride to glycogen in liver than cows fed CE diets. In conclusion, cows fed CE diets during the CU period had a shorter interval between parturition and conception, which may be explained by increased NEL intake during the first 4wk postpartum and lower incidence of peripartal diseases. Lower body condition score loss during the first 6wk postpartum and slightly higher glucose concentration at wk 3 likely contributed to improved reproductive performance.

Embryo survival, progesterone profiles and metabolic responses to an increased feeding level during second gestation in sows

This study describes reproductive and metabolic responses in sows fed at two different feeding levels from day 3–35 of second gestation. After insemination, 37 sows were assigned to one of two treatments: 1) Control: 2.5 kg/day of a gestation diet; 2) Plus Feed 3.25 kg/day of a gestation diet (+30%). Sow weight, back fat and loin muscle depth were measured at farrowing, weaning, start of treatment, day 14 after start treatment and end of treatment. Frequent blood samples were taken for progesterone, luteinizing hormone (LH), glucose and insulin, insulin-like-growth-factor-1 (IGF-1), non-esterified-fatty-acids (NEFA) and urea analysis. At day 35 after insemination sows were euthanized and their reproductive tract collected to assess ovarian, embryonic and placental characteristics. Plus Feed sows gained 5.4 kg more weight and 0.9 mm more back fat and tended to be heavier at slaughter compared to Control sows (193 vs. 182 kg, P = 0.06). No difference in loin muscle gain was found. Treatment also did not affect vital embryonic survival, which was 72.1 ± 3.9% for Control and 73.4 ± 3.2% for Plus Feed sows, resulting in, respectively, 15.9 ± 0.9 and 15.7 ± 0.7 vital embryos. No effect of treatment on any of the ovarian, embryonic or placental characteristics was found. Progesterone profiles during the first month of gestation, and LH characteristics at day 14 of gestation were not different between treatments. Progesterone concentration was lower (P < 0.05) 3 h after feeding compared with the prefeeding level on days 7–11 after first progesterone rise for Plus Feed and on days 8–10 after first progesterone rise for Control sows. At day 15, preprandial glucose and insulin concentrations were not different between treatments, insulin peaked later (48 vs. 24 min) and at a higher concentration in Plus Feed than in Control sows. Furthermore, glucose area under the curve (AUC) tended to be lower (−171.7 ± 448.8 vs. 1257.1 ± 578.9 mg/6.2 h, P = 0.06, respectively) for Plus Feed vs. Control sows. IGF-1 concentration was not different between treatments, but NEFA concentrations were lower for Plus Feed vs. Control sows (149.5 ± 9.2 vs. 182.4 ± 11.9 μm/L, respectively, P = 0.04) and urea concentration tended to be higher in Plus Feed than in Control sows (4.3 ± 0.1 vs. 3.9 ± 0.1, respectively, P = 0.13). None of the metabolic parameteres were related to reproductive measures. In conclusion, feeding 30% more feed from day 3 till d 35 of second gestation increased weight gain and resulted in lower NEFA concentrations, but did not affect progesterone, LH or IGF-1 and embryonic and placental characteristics.

The association of serum metabolites with clinical disease during the transition period

The objective of this observational field study was to validate the relationship of serum concentrations of nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and calcium with disease in early lactation across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were selected and visited weekly for blood sample collection from 2,365 cows. Only diseases that were consistently recorded across herds and blood samples collected before the disease occurred were considered. Metabolite concentrations in serum in wk −1 relative to calving were considered as predictors of retained placenta (RP) and metritis, and metabolite concentrations in serum in wk −1 and wk +1 relative to calving were considered as predictors of displaced abomasum (DA). For each disease, each metabolite, and week of sampling in the case of DA, a critical threshold was calculated based on the highest combined sensitivity and specificity and used to categorize the serum concentrations into high and low risk categories. Multivariable logistic regression models were built for each disease of interest and week of sampling, considering cow as the experimental unit and herd as a random effect. Cows with precalving serum NEFA concentrations ≥0.3mEq/L were more likely to develop RP [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.3 to 2.6] and metritis (OR = 1.8; 95% CI=1.5 to 2.9) after calving than cows with lower NEFA concentrations. Precalving NEFA ≥0.5mEq/L (OR=2.4; 95% CI=1.5 to 3.7), postcalving NEFA ≥1.0mEq/L (OR=2.7; 95% CI=1.7 to 4.4), and postcalving calcium ≤2.2mmol/L (OR=3.1; 95% CI=1.9 to 5.0) were associated with subsequent risk of DA. In conclusion, elevated serum NEFA concentrations within 1 wk before calving were associated with increased risk of RP, metritis, and DA after calving. Serum NEFA and calcium concentrations in the 2 wk around calving in combination were associated with the risk of DA.

High NEFA concentrations around parturition are associated with delayed ovulations in grazing dairy cows

The objectives of this study were to assess indicators of metabolic status of grazing dairy cows around parturition, and the relationship between these indicators with the resumption of ovulations postpartum (ROP). Holstein multiparous cows (N=20) grazing on improved pastures and supplemented with concentrates were body condition scored and tail bled weekly from wk −2 through +9 related to parturition. Plasma samples were analyzed for non-esterified fatty acids (NEFA), leptin, insulin-like growth factor-1 (IGF-1) and progesterone (P4). Data were analyzed with mixed models, logistic regression, with receiver operator characteristic (ROC), and Cox regression analysis. Cows having Delayed Ovulation ([DO], ROP on week ≥5) had lower BCS, and higher NEFAs than cows having a normal ROP around parturition (BCS: 2.73±0.08 vs. 2.94±0.05, P<0.05, and NEFA: 0.43±0.04 vs. 0.35±0.02mM, P<0.10, respectively). Also, DO cows had lower BCS than normal herdmates (2.59±0.10 vs. 2.99±0.06, P<0.01) around time of ROP, but they had similar NEFA, leptin and IGF-1. The risk for DO increased as NEFA increased (0.4% and 0.5% per every increasing mM of NEFA in prepartum and postpartum, respectively). The ROC curve showed that NEFA (prepartum and postpartum) had areas of 0.85 and 0.80, and cut-off values of 0.39 and 0.47mM. Finally, hazard for ROP increased as prepartum IGF-1 increased, and it decreased as postpartum NEFA increased. In conclusion, cows with lower BCS and higher prepartum and postpartum NEFA had higher odds for getting DO than herdmates with greater BCS and lower NEFA concentrations.

Peripartum responses of dairy cows to prepartal feeding level and dietary fatty acid source

This experiment was conducted to investigate the effect of feeding level and oilseed supplementation during the close-up dry period on energy balance (EB), hepatic lipidosis, metabolic status, and productivity in early lactation. Seventy-seven Holstein cows were blocked according to parity and expected calving date and then assigned randomly to 1 of 6 treatments in a 2 × 3 factorial allocation with 2 feeding levels: ad libitum (AL) or 30% feed restriction (FR), and 3 dietary fatty acid sources: canola seed, linola seed, or flaxseed at 8% of dietary dry matter (DM), to enrich the rations with oleic, linoleic, or linolenic acids, respectively during the last 4 wk of gestation. After parturition, all cows were fed a common lactation diet. Cows fed AL lost less body weight (−2.9 vs. −6.0%) and body condition score (+0.67 vs. −2.30%), and consequently were in more positive EB (+4.6 vs. −0.3 Mcal) during the prepartum period than cows subjected to FR. Postpartum, FR cows lost less body weight (−9.7 vs. −12.4%) and experienced less severe negative EB (−4.5 vs. −7.0 Mcal) than AL cows. Cows fed AL had higher plasma insulin (6.8 vs. 4.4 μIU/mL) and lower nonesterified fatty acid concentrations (436 vs. 570 mEq/mL) during the close-up period than cows subjected to FR. Cows fed AL tended to have lower liver glycogen content in early lactation than cows subjected to FR (4.4 vs. 2.9 μg/g of DM), but had similar triglyceride content (13.1±1.2 μg/g of DM). Fatty acid source did not influence response variables. In conclusion, eliminating intake depression by FR during the close-up period had positive carryover effects on EB and metabolic status during early lactation, but feeding linoleic and linolenic acids via unprotected oilseeds only had negligible effects on peripartum responses.

Performance and amino acid utilization of early lactation dairy cows fed regular or reduced-fat dried distillers grains with solubles

The objective of this study was to evaluate lactation response and AA utilization of early lactation cows fed 2 types of dried distillers grains with solubles (DG): regular (DDGS) or reduced-fat (RFDGS). Thirty-six Holstein cows 19.7±2.6 d in milk at the start of the experiment were used in a randomized complete block design for 14 wk including a 2-wk covariate period. Treatments consisted of the following diets: 1) control (CON) diet containing 0% DG; 2) diet containing 22% DDGS; and 3) diet containing 20% RFDGS. Distillers grains replaced soybean meal, expeller soybean meal, and soyhulls from the CON diet. Diets were formulated to be similar in crude protein, ether extract, neutral detergent fiber, and net energy for lactation concentrations. Dry matter intake (24.7 kg/d) and milk yield (39.3 kg/d) were similar for all diets. Milk fat and lactose percentages were unaffected by diets; however, protein percentage was greater for cows fed the DG diets compared with the CON diet. Consequently, milk protein yield was also greater for the DG diets compared with CON. Milk urea nitrogen decreased for cows fed DG diets and averaged 11.8, 10.9, and 10.1 mg/dL, respectively, for CON, DDGS, and RFDGS. Feed efficiency tended to be greater and N efficiency was greater for cows fed DG compared with CON. Body weight (711kg), body weight change (+0.49 kg/d), and body condition score (3.36) were similar for all diets, but cows fed CON tended to gain more body condition (+0.14) than cows fed DG diets. Amino acid utilization was evaluated at the peak of milk production corresponding to wk 9 of lactation. Arterial Lys concentration was lower with DG diets (70.4, 58.6, and 55.8 μM/L). Cows fed DG had greater arterial Met concentration (21.3 μM) compared with CON (14.9 μM). Arterio-venous difference of Lys was similar across diets, whereas that of Met was greater for the DG diets compared with the CON diet (10.3 vs. 13.0 μM/L). Extraction efficiency of Lys by the mammary gland was greater for DG diets than for CON (76.1 vs. 65.4%). Mammary uptake of Lys (2.56 g/kg of milk) was similar for all diets, and the uptake of Met tended to increase in cows fed DG diets. Plasma glucose, triglyceride, and total cholesterol were unaffected by treatment; however, cows fed DG diets had lower β-hydroxybutyrate and tended to have lower nonesterified fatty acid concentrations than cows fed the CON diet. Despite the apparent deficiency of Lys, milk protein percentage was increased in cows fed DG diets.

Effect of dietary fats with odd or even numbers of carbon atoms on metabolic response and muscle damage with exercise in Quarter Horse–type horses with type 1 polysaccharide storage myopathy

To evaluate effects of fats with odd and even numbers of carbon atoms on muscle metabolism in exercising horses with polysaccharide storage myopathy (PSSM). 8 horses with PSSM (6 females and 2 males; mean +/- SD age, 6.3 +/- 3.9 years). Isocaloric diets (grain, triheptanoin, corn oil, and high-fat, low-starch [HFLS] feed) were fed for 3 weeks each; horses performed daily treadmill exercise. Grain was fed to establish an exercise target, and HFLS feed was fed as a negative control diet. Daily plasma samples were obtained. For each diet, a 15-minute exercise test was performed, and gluteus medius muscle specimens and blood samples were obtained before and after exercise. Feeding triheptanoin, compared with the corn oil diet, resulted in exercise intolerance; higher plasma creatine kinase (CK) activity and concentrations of C3:0- and C7:0-acylcarnitine and insulin; and lower concentrations of nonesterified fatty acids (NEFA) and C16:0-, C18:1-, and C18:2-acylcarnitine, without changes in concentrations of plasma glucose or resting muscle substrates and metabolites. Feeding grain induced higher CK activity and insulin concentrations and lower NEFA concentrations than did corn oil or HFLS feed. Feeding grain induced higher glucose concentrations than did triheptanoin and corn oil. In muscle, feeding grain resulted in lower glucose-6-phosphate, higher citrate, and higher postexercise lactate concentrations than did the other diets. Triheptanoin had detrimental effects, reflecting decreased availability of NEFA, increased insulin stimulation of glycogen synthesis, and potential inhibition of lipid oxidation. Long-chain fats are the best dietetic for PSSM.

Improved Metabolic Control After 12-Week Dietary Intervention with Low Glycaemic Isomalt in Patients with Type 2 Diabetes Mellitus

The polyol isomalt (Palatinit) is a very low glycaemic sugar replacer. The effect of food supplemented with isomalt instead of higher glycaemic ingredients like sucrose and/or starch hydrolysates on metabolic control in patients with type 2 diabetes was examined in this open study. Thirty-three patients with type 2 diabetes received a diet with foods containing 30 g/d isomalt instead of higher-glycaemic carbohydrates for 12 weeks. Metformin and/or thiazolidindiones were the only concomitant oral antidiabetics allowed during the study. Otherwise, the participants maintained their usual diet during the test phase, but were instructed to refrain from additional sweetened foods. Before start, after 6 weeks and 12 weeks (completion of the study), blood samples were taken and analysed for clinical routine parameters, metabolic, and risk markers. Thirty-one patients completed the study. The test diet was well accepted and tolerated. After 12 weeks, significant reductions were observed for: glycosylated haemoglobin, fructosamine, fasting blood glucose, insulin, proinsulin, C-peptide, insulin resistance (HOMA-IR), and oxidised LDL (an atherosclerosis risk factor). In addition, significant lower nonesterified fatty acid concentrations were found in female participants. Routine blood measurements and blood lipids remained unchanged. The substitution of glycaemic ingredients by isomalt and the consequent on reduction of the glycaemic load within otherwise unchanged diet was accompanied by significant improvement in the metabolic control of diabetes. The present study is in agreement with findings of previous reported studies in human subjects demonstrating beneficial effects of low glycaemic diets on glucose metabolism in patients with diabetes mellitus type 2.

Interrelations Between Glucose-Induced Insulin Response, Metabolic Indicators, and Time of First Ovulation in High-Yielding Dairy Cows

High-yielding dairy cows are more susceptible to metabolic and reproductive disorders than low-yielding cows. Insulin plays a pivotal role in the development of both problems. In the present study, we aimed to assess the glucose-induced insulin responses of dairy cows at different time points relative to calving and to relate this to the metabolic status and the time of first ovulation. Twenty-three healthy, multiparous Holstein-Friesian cows with a high genetic merit for milk yield were studied from 14 d prepartum to 42 d postpartum. Intravenous glucose tolerance tests were performed on −14, 14, and 42 d relative to calving to evaluate the plasma insulin and glucose responses to a glucose load, as estimated by the peak concentration, the area under the curve (AUC), and the clearance rates of insulin and glucose. Blood samples were obtained at 3-d intervals and analyzed for glucose, insulin, and nonesterified fatty acids (NEFA). The time of first ovulation was defined by transrectal ultrasonography and plasma progesterone analysis. Glucose-induced insulin AUC and peak concentration decreased and glucose clearance increased during lactation compared with the dry period. Plasma NEFA concentrations were negatively related to insulin AUC and peak concentrations. Fourteen cows ovulated within 42 d postpartum, and the remaining 9 cows suffered from delayed resumption of ovarian function. Survival analysis demonstrated that cows with lower NEFA concentrations during the dry period tended to have earlier resumption of ovarian activity. In conclusion, our data suggest a decreased plasma insulin response to glucose postpartum in high-yielding dairy cows, possibly contributing to metabolic stress during the early postpartum period. It is hypothesized that NEFA impair glucose-induced insulin secretion in dairy cows. Additionally, our results suggest the importance of lipolysis during the transition period as a risk factor for delayed ovulation.

Putting your genes on a diet: the molecular effects of carbohydrate

Traditionally, food is thought to influence human health through its nutrient content, whereas drugs are recognized to act through molecular pathways. However, consumption of a meal stimulates the release of numerous hormones that can powerfully affect signal transduction and gene function. The article by Kallio et al (1) in this issue of the Journal highlights this possibility by demonstrating changes in gene expression in individuals consuming diets with different effects on postprandial insulin concentrations. The authors randomly assigned adults with features of the metabolic syndrome to a rye-pasta (low insulin response) or an oat-wheat-potato (high insulin response) diet for 12 wk. The diets were designed to be similar in energy, fiber, and macronutrient contents, although modest differences in fiber, carbohydrate, and protein contents were documented by food records. Gene expression in subcutaneous fat was evaluated at baseline and at 12 wk with microarrays and quantitative polymerase chain reaction. In individuals in the low-insulin-response group, 71 genes showed decreased expression and none showed increased expression. Of particular interest, several down-regulated genes have links to insulin-signaling pathways and apoptosis. In contrast, in individuals in the high-insulin-response group, 62 genes showed increased expression and none showed decreased expression. Prior microarray studies found differences in gene expression between overweight and lean individuals (2) and after energy restriction (3); however, changes in the ratio of fat to carbohydrate did not alter gene expression (3). The study by Kallio et al makes a significant contribution to the literature by demonstrating the potentially major effects of dietary composition on gene regulation, independent of energy intake and body weight. Two specific findings concerning the low-insulin-response diet merit particular attention: the down-regulation of both hormonesensitive lipase (HSL) and TCF7L2. HSL, a key enzyme in the release of fatty acids from adipose tissue, has been proposed to affect body weight and metabolic variables. Mice made deficient in HSL by genetic manipulation are resistant to geneticor diet-induced obesity (4, 5). Women carrying an allele associated with decreased HSL activity have lower fasting and simulated insulin concentrations, and men with this allele have lower nonesterified fatty acid concentrations (6). In light of these data, proteins involved in lipolysis have become targets of drug development for the treatment of obesity and the metabolic syndrome. Thus, decreased HSL activity might mediate some of the purported benefits of diets designed to lower insulin secretion. The transcription factor TCF7L2 is the strongest known genetic predictor of type 2 diabetes. A microsatellite within intron 3 of this transcription factor occurs with increased frequency in individuals with type 2 diabetes, which corresponds to an estimated population attributable risk of 21% (7). Although the mechanisms involved in disease risk have not been fully elucidated, TCF7L2 affects the Wnt signaling pathway and may be critical for glucagon-like peptide 1 (GLP-1) secretion by intestinal endocrine L cells. Decreased secretion of GLP-1 appears to play a role in the development of type 2 diabetes, and GLP-1 agonists have recently been developed for the treatment of diabetes. The present study has direct implications concerning our understanding of the dietary glycemic index (GI). The GI is a system for classifying carbohydrate-containing foods according to how blood glucose concentrations change in the postprandial period (reviewed in reference 8). High-GI meals produce greater postprandial insulin concentrations and C-peptide excretion than do nutrient-controlled low-GI meals. Observational and interventional studies have linked GI to the risk of obesity, diabetes, heart disease, and cancer, although the topic remains much debated. One factor contributing to this ongoing controversy is the relative paucity of data regarding the relevant molecular mechanisms. If differences in insulin secretion mediate the genetic effects observed by Kallio et al, similar effects would be expected to occur with both low-GI and high-GI diets. This possibility is supported by a human study and several rodent studies, which showed potentially beneficial changes in the expression of HSL and other relevant genes with a low-GI diet (8, 9). Several methodologic issues should be considered in the interpretation of this study. Microarray analyses have well-known technical limitations and statistical problems, especially when involving small sample sizes (10). The unidirectional change in gene expression within each diet group provides some grounds

Peripartum Responses of Dairy Cows Fed Energy-Dense Diets for 3 or 6 Weeks Prepartum

Pregnant cows (n=189) in two commercial dairy farms were assigned randomly to be fed energy-dense diets for either 3 or 6 wk before expected calving. Cows fed diets for less than or equal to 26 d were designated the short (S) treatment group, and those fed greater than 26 d were the long (L) treatment group. Cows in L tended to have improved energy status during the first 2 wk postpartum, as indicated by higher insulin concentrations and a tendency for lower nonesterified fatty acid concentrations. Treatment did not affect plasma β-hydroxybutyrate concentrations. Cows in L tended to gain more body condition during the late dry period. Total body condition loss from parturition through 6 wk postpartum was not different between treatments, but the rate of change varied over this period. Cows in S lost more body condition during the first 3 wk postpartum than cows in L. In farm 1 only, cows in L lost more body condition from 3 to 6 wk postpartum and had a higher incidence of metritis and a longer interval to first service than cows in S. Cows in L had higher milk protein content through 60 d in milk compared with cows in S. Additionally, cows in L in farm 1 produced 4.4kg/d less milk, tended to have lower milk fat content and yields, and higher somatic cell counts through 150 d in milk than cows in S. Overall, increasing the length of time cows were fed the energy-dense diet prepartum elicited significant changes in farm 1, but had little effect in farm 2. Based on these results, L treatment may improve energy status immediately postpartum, but long-term effects varied between farms, perhaps due to other unmeasured management differences.

Effect of the antiobesity agent sibutramine in obese-diabetic ob/ob mice.

Sibutramine is a reuptake inhibitor of 5-hydroxytryptamine and noradrenaline, being developed as a treatment for obesity. To investigate the effect of sibutramine on glucose homeostasis in obese-hyperglycaemic insulin-resistant ob/ob mice. Sibutramine 5 mg/kg once daily was administered orally to ob/ob mice for six weeks. Sibutramine treatment decreased body weight gain by 12% without a significant overall change in daily food intake. Sibutramine reduced the hyperinsulinaemia by 31%, and lowered plasma non-esterified fatty acids (NEFA) by 17%. Basal plasma glucose concentrations were not significantly altered by sibutramine, but glucose concentrations fell more rapidly after an i.p. glucose challenge, despite lower insulin concentrations. The rate of insulin-induced glucose disappearance was increased by 10% during sibutramine treatment. First administration of sibutramine, 5 mg/kg, did not acutely alter basal plasma glucose, insulin or NEFA concentrations in ob/ob mice, although NEFA concentrations were raised after 24 h. The results indicate that chronic administration of sibutramine can reduce weight gain, lower NEFA concentrations, decrease hyperinsulinaemia and ameliorate the insulin resistance of ob/ob mice.

Plasma non-esterified fatty acid response to dialysate acetate concentration during haemodialysis in humans

We have inhibited the in vitro generation of non-esterified fatty acids in plasma samples taken during haemodialysis by cooling the samples rapidly, centrifuging and freezing within 5 min of sampling and completing the assay on the same day. The relationship of non-esterified fatty acid concentrations during haemodialysis to the acetate concentration of the dialysate and the profile of circulating lipase activities was studied. With this sample-handling protocol we found lower non-esterified fatty acid concentrations than reported in many other studies and the results suggest that, under normal conditions of haemodialysis, the circulating non-esterified fatty acid concentrations and the associated risk of unwanted side-effects may have been previously over-estimated due to artefactual in vitro sample lipolysis. We also showed that, at the end of dialysis, when circulating lipase activities were least, the non-esterified fatty acid concentrations were lower ( P < 0.05) with an acetate dialysate containing 37 mmol/l acetate than with a bicarbonate dialysate containing 3 mmol/l acetate.