- Andre J. Pantophlet (3)
- Joost J.G.C. Borne Van Den (1)
- Walter J.J. Gerrits (1)
- Marcel P. Vries de (1)
- A.J. Pantophlet (11)
- A.M. Pluschke (1)
- M.G. Priebe (2)
- H. Roelofsen (2)
- H.A. Schols (7)
- R.J. Vonk(older publications) (3)
- R.J. Vonk (2)
|Glucose homeostasis and insulin resistance in veal calves
Pantophlet, Andre J. - \ 2018
University of Groningen. -
Short communication : Supplementation of fructo-oligosaccharides does not improve insulin sensitivity in heavy veal calves fed different sources of carbohydrates
Pantophlet, Andre J. ; Gilbert, M.S. ; Gerrits, W.J.J. ; Vonk, R.J. - \ 2017
Journal of Dairy Science 100 (2017)11. - ISSN 0022-0302 - p. 9442 - 9446.
Fructo-oligosaccharides - Insulin sensitivity - Milk replacer - Veal calf
Heavy veal calves (4-6 mo old) often develop problems with insulin sensitivity. This could lead to metabolic disorders and impaired animal growth performance. Studies in various animal species have shown that the supplementation of short-chain fructo-oligosaccharides (scFOS) can improve insulin sensitivity. We therefore studied the effects of scFOS supplementation on insulin sensitivity in heavy veal calves. Forty male Holstein-Friesian calves (BW = 190 ± 2.9 kg; age = 162 ± 1.4 d at the start of the trial) were fed either a control milk replacer (MR) diet or a diet in which one-third of the lactose was replaced by glucose, fructose, or glycerol for 10 wk prior to the start of the trial. At the start of the trial, calves were subjected to a frequently sampled intravenous glucose tolerance test to assess whole-body insulin sensitivity (muscle and hepatic insulin sensitivity). Calves within each dietary treatment group were ranked based on their insulin sensitivity value. Half of the calves received scFOS (12 mg/kg of BW) with the MR for 6 wk (supplementation was equally distributed over the insulin sensitivity range). Subsequently, a second frequently sampled intravenous glucose tolerance test was conducted to assess the effect of scFOS. In addition, fasting plasma levels of glucose, insulin, triglycerides, and cholesterol were determined to calculate the quantitative insulin sensitivity check index and triglyceride:high-density lipoprotein cholesterol ratio (fasting indicators of insulin sensitivity). Whole-body insulin sensitivity was low at the start of the trial and remained low in all groups [1.0 ± 0.1 and 0.8 ± 0.1 (mU/L)-1 · min-1 on average, respectively]. Supplementation of scFOS did not improve insulin sensitivity in any of the treatment groups. The quantitative insulin sensitivity check index and the triglyceride:high-density lipoprotein cholesterol ratio also did not differ between scFOS and non-scFOS calves and averaged 0.326 ± 0.003 and 0.088 ± 0.004, respectively, at the end of the trial. We conclude that scFOS supplementation does not improve insulin sensitivity in heavy veal calves regardless of the carbohydrate composition of the MR. This is in contrast to other animals (e.g., dogs and horses), where scFOS supplementation did improve insulin sensitivity. The absence of an effect of scFOS might be related to the dosage or to metabolic differences between ruminants and nonruminants. Increasing evidence indicates that dietary interventions in veal calves have little or no effect on insulin sensitivity, possibly because of low levels of insulin sensitivity.
The use of metabolic profiling to identify insulin resistance in veal calves
Pantophlet, Andre J. ; Roelofsen, H. ; Vries, Marcel P. de; Gerrits, Walter J.J. ; Borne, Joost J.G.C. Van Den; Vonk, R.J. - \ 2017
PLoS ONE 12 (2017)6. - ISSN 1932-6203 - 12 p.
Heavy veal calves (4–6 months old) are at risk of developing insulin resistance and disturbed glucose homeostasis. Prolonged insulin resistance could lead to metabolic disorders and impaired growth performance. Recently, we discovered that heavy Holstein-Friesian calves raised on a high-lactose or high-fat diet did not differ in insulin sensitivity, that insulin sensitivity was low and 50% of the calves could be considered insulin resistant. Understanding the patho-physiological mechanisms underlying insulin resistance and discovering biomarkers for early diagnosis would be useful for developing prevention strategies. Therefore, we explored plasma metabolic profiling techniques to build models and discover potential biomarkers and pathways that can distinguish between insulin resistant and moderately insulin sensitive veal calves. The calves (n = 14) were classified as insulin resistant (IR) or moderately insulin sensitive (MIS) based on results from a euglycemic-hyperinsulinemic clamp, using a cut-off value (M/I-value <4.4) to identify insulin resistance. Metabolic profiles of fasting plasma samples were analyzed using reversed phase (RP) and hydrophilic interaction (HILIC) liquid chromatography–mass spectrometry (LC-MS). Orthogonal partial least square discriminant analysis was performed to compare metabolic profiles. Insulin sensitivity was on average 2.3x higher (P <0.001) in MIS than IR group. For both RP-LC-MS and HILIC-LC-MS satisfactory models were build (R2Y >90% and Q2Y >66%), which allowed discrimination between MIS and IR calves. A total of 7 and 20 metabolic features (for RP-LC-MS and HILIC-LC-MS respectively) were most responsible for group separation. Of these, 7 metabolites could putatively be identified that differed (P <0.05) between groups (potential biomarkers). Pathway analysis indicated disturbances in glycerophospholipid and sphingolipid metabolism, the glycine, serine and threonine metabolism, and primary bile acid biosynthesis. These results demonstrate that plasma metabolic profiling can be used to identify insulin resistance in veal calves and can lead to underlying mechanisms.
Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves
Pantophlet, A.J. ; Gerrits, W.J.J. ; Vonk, R.J. ; Borne, J.J.G.C. van den - \ 2016
Journal of Dairy Science 99 (2016)12. - ISSN 0022-0302 - p. 10022 - 10032.
Fat - Insulin sensitivity - Lactose - Veal calves
In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120 ± 2.8 kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2 ± 0.5 × 10-2 [(mg/kg·min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75 ± 13 g/d) than in HF calves (21 ± 6 g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5 ± 0.6 g/kg, but liver triglyceride content was higher in HF calves (16.4 ± 0.9 g/kg) than in HL calves (11.2 ± 0.7 g/kg), indicating increased hepatic fat accumulation. We conclude that increasing the contribution of fat to the digestible energy intake from the MR from 20 to 50%, at the expense of lactose does not affect whole-body insulin sensitivity and insulin secretion in calves. However, a high-lactose MR increases postprandial glucose and insulin responses, whereas a high-fat MR increases fat accumulation in liver but not muscle.
Insulin sensitivity in calves decreases substantially during the first 3 months of life and is unaffected by weaning or fructo-oligosaccharide supplementation
Pantophlet, A.J. ; Gilbert, M.S. ; Borne, J.J.G.C. van den; Gerrits, W.J.J. ; Priebe, M.G. ; Vonk, R.J. - \ 2016
Journal of Dairy Science 99 (2016)9. - ISSN 0022-0302 - p. 7602 - 7611.
Veal calves at the age of 4 to 6 mo often experience problems with glucose homeostasis, as indicated by postprandial hyperglycemia, hyperinsulinemia, and insulin resistance. It is not clear to what extent the ontogenetic development of calves or the feeding strategy [e.g., prolonged milk replacer (MR) feeding] contribute to this pathology. The objective of this study was therefore to analyze effects of MR feeding, weaning, and supplementation of short-chain fructo-oligosaccharides (FOS) on the development of glucose homeostasis and insulin sensitivity in calves during the first 3 mo of life. Thirty male Holstein-Friesian calves (18 ± 0.7 d of age) were assigned to 1 of 3 dietary treatments: the control (CON) group received MR only, the FOS group received MR with the addition of short-chain FOS, and the solid feed (SF) group was progressively weaned to SF. The CON and FOS calves received an amount of MR, which gradually increased (from 400 to 1,400 g/d) during the 71-d trial period. For the SF calves, the amount of MR increased from 400 to 850 g/d at d 30, and then gradually decreased, until completely weaned to only SF at d 63. The change in whole body insulin sensitivity was assessed by intravenous glucose tolerance tests. Milk tolerance tests were performed twice to assess changes in postprandial blood glucose, insulin, and nonesterified fatty acid responses. Whole-body insulin sensitivity was high at the start (16.7 ± 1.6 × 10−4 [μU/mL]−1), but decreased with age to 4.2 ± 0.6 × 10−4 [μU/mL]−1 at the end of the trial. The decrease in insulin sensitivity was most pronounced (∼70%) between d 8 and 29 of the trial. Dietary treatments did not affect the decrease in insulin sensitivity. For CON and FOS calves, the postprandial insulin response was 3-fold higher at the end of the trial than at the start, whereas the glucose response remained similar. The SF calves, however, showed pronounced hyperglycemia and hyperinsulinemia at the end of the trial, although weaning did not affect insulin sensitivity. We conclude that whole body insulin sensitivity decreases by 75% in calves during the first 3 mo of life. Weaning or supplementation of short-chain FOS does not affect this age-related decline in insulin sensitivity. Glucose homeostasis is not affected by supplementation of short-chain FOS in young calves, whereas postprandial responses of glucose and insulin to a MR meal strongly increase after weaning.
Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves
Pantophlet, A.J. ; Gilbert, M.S. ; Borne, J.J.G.C. van den; Gerrits, W.J.J. ; Roelofsen, H. ; Priebe, M.G. ; Vonk, R.J. - \ 2016
Journal of Dairy Science 99 (2016)4. - ISSN 0022-0302 - p. 3072 - 3080.
Fructose - Glucose homeostasis - Glycerol - Insulin sensitivity - Veal calves
Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100 kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight = 114 ± 2.4 kg; age = 97 ± 1.4 d) calves were fed an MR containing 462 g of lactose/kg (CON), or an MR in which 150 g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10 d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5 g of [U-13C] substrates was added to their respective meals and plasma glucose, insulin, and 13C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2 ± 0.1 and 1.0 ± 0.1 (mU/L)-1 × min-1], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4 ± 1.0 g/d), but increased (P <0.01) in CON and GLU calves (26.9 ± 3.9 and 43.0 ± 10.6 g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU and GLY and similar in GLU compared with CON calves. Postprandial 13C-glucose increased substantially in FRU and GLY calves, indicating that calves are able to partially convert these substrates to glucose. We concluded that replacing one third of lactose in MR by glucose, fructose, or glycerol in MR differentially influences postprandial glucose homeostasis but does not affect insulin sensitivity in veal calves.
Effects of replacing lactose from milk replacer by glucose, fructose, or glycerol on energy partitioning in veal calves
Gilbert, M.S. ; Pantophlet, A.J. ; Borne, J.J.G.C. van den; Hendriks, W.H. ; Schols, H.A. ; Gerrits, W.J.J. - \ 2016
Journal of Dairy Science 99 (2016)2. - ISSN 0022-0302 - p. 1121 - 1132.
Energy retention - Fructose - Glucose - Glycerol - Veal calf
Calf milk replacers contain 40 to 50% lactose. Fluctuating dairy prices are a major economic incentive to replace lactose from milk replacers by alternative energy sources. Our objective was, therefore, to determine the effects of replacement of lactose with glucose, fructose, or glycerol on energy and protein metabolism in veal calves. Forty male Holstein-Friesian calves (114 ± 2.4 kg) were fed milk replacer containing 46% lactose (CON) or 31% lactose and 15% of glucose (GLUC), fructose (FRUC), or glycerol (GLYC). Solid feed was provided at 10 g of dry matter (DM)/kg of metabolic body weight (BW0.75) per day. After an adaptation of 48 d, individual calves were harnessed, placed in metabolic cages, and housed in pairs in respiration chambers. Apparent total-tract disappearance of DM, energy, and N and complete energy and N balances were measured. The GLUC, FRUC, and GLYC calves received a single dose of 1.5 g of [U-13C]glucose, [U-13C]fructose, or [U-13C]glycerol, respectively, with their milk replacer at 0630 h and exhaled 13CO2 and 13C excretion with feces was measured. Apparent total-tract disappearance was decreased by 2.2% for DM, 3.2% for energy, and 4.2% for N in FRUC compared with CON calves. Energy and N retention did not differ between treatments, and averaged 299 ± 16 kJ/kg of BW0.75 per day and 0.79 ± 0.04 g/kg of BW0.75 per day, respectively, although FRUC calves retained numerically less N (13%) than other calves. Recovery of 13C isotopes as 13CO2 did not differ between treatments and averaged 72 ± 1.6%. The time at which the maximum rate of 13CO2 production was reached was more than 3 h delayed for FRUC calves, which may be explained by a conversion of fructose into other substrates before being oxidized. Recovery of 13C in feces was greater for FRUC calves (7.7 ± 0.59%) than for GLUC (1.0 ± 0.27%) and GLYC calves (0.5 ± 0.04%), indicating incomplete absorption of fructose from the small intestine resulting in fructose excretion or fermentation. In conclusion, energy and N retention was not affected when replacing >30% of the lactose with glucose, fructose, or glycerol. Increased fecal losses of DM, energy, and N were found in FRUC calves compared with CON, GLUC, and GLYC calves. Postabsorptive losses occurred with the urine for glucose and glycerol, which caused a lower respiratory quotient for GLUC calves during the night. Fructose was oxidized more slowly than glucose and glycerol, probably as a result of conversion into other substrates before oxidation.
Fermentation in the small intestine contributes substantially to intestinal starch disappearance in calves
Gilbert, M.S. ; Pantophlet, A.J. ; Berends, H. ; Pluschke, A.M. ; Borne, J.J.G.C. van den; Hendriks, W.H. ; Schols, H.A. ; Gerrits, W.J.J. - \ 2015
The Journal of Nutrition 145 (2015)6. - ISSN 0022-3166 - p. 1147 - 1155.
Background: The proportion of starch disappearing from the small intestinal lumen is generally lower in ruminants than in monogastric animals, and there are indications that the starch digestion capacity in ruminants is limited. Objectives: Milk-fed calves were used to study the rate-limiting enzyme in starch hydrolysis and to quantify starch fermentation in ruminants. Methods: Forty male Holstein-Friesian calves were fed milk replacer containing either lactose (control) or 1 of 4 corn starch products. The following starch products differed in the enzyme ratios required for their complete hydrolysis to glucose: gelatinized starch [a-amylase and (iso)maltase], maltodextrin [(iso)maltase and a-amylase], maltodextrin with a-1,6-branching (isomaltase, maltase, and a-amylase), and maltose (maltase). In the adaptation period, calves were stepwise exposed to an increasing dose of the starch product for 14 wk to allow maximal adaptation of all enzyme systems involved. In the experimental period, apparent total tract and ileal starch product disappearance, total tract starch product fermentation, and a-amylase, maltase, and isomaltase activities were determined at 18% inclusion of the starch product. Results: Maltase and isomaltase activities in the brush border did not increase for any of the starch product treatments. Luminal a-amylase activity was lower in the proximal (3.9 ± 3.2 and 2.7 ± 1.7 U/mg Co for control and starch product calves, respectively) but greater in the distal small intestine of starch-fed calves than in control calves (0.0 ± 0.0 and 6.4 ± 1.5 U/mg Co for control and starch product calves, respectively; means ± SEs for control and means ± pooled SEMs for starch product treatments). Apparent ileal (61.6% ± 6.3%) and total tract (99.1% ± 0.4%) starch product disappearance did not differ between starch product treatments, suggesting that maltase activity limits starch digestion in ruminants. Total tract starch product fermentation averaged 414 ± 43 g/d, corresponding to 89% of intake, of which half was fermented before the terminal ileum, regardless of starch product treatment. Conclusion: Fermentation, rather than enzymatic digestion, is the main reason for small intestinal starch disappearance in milk-fed calves.
A titration approach to identify the capacity for starch digeston in milk-fed calves
Gilbert, M.S. ; Borne, J.J.G.C. van den; Berends, H. ; Pantophlet, A.J. ; Schols, H.A. ; Gerrits, W.J.J. - \ 2015
Animal 9 (2015)2. - ISSN 1751-7311 - p. 249 - 257.
small-intestinal disappearance - abomasal glucose - maize starch - amylase - steers - oligosaccharide - digestibility - secretion - replacers - infusion
Calf milk replacers (MR) commonly contain 40% to 50% lactose. For economic reasons, starch is of interest as a lactose replacer. Compared with lactose, starch digestion is generally low in calves. It is, however, unknown which enzyme limits the rate of starch digestion. The objectives were to determine which enzyme limits starch digestion and to assess the maximum capacity for starch digestion in milk-fed calves. A within-animal titration study was performed, where lactose was exchanged stepwise for one of four starch products (SP). The four corn-based SP differed in size and branching, therefore requiring different ratios of starch-degrading enzymes for their complete hydrolysis to glucose: gelatinised starch (a-amylase and (iso)maltase); maltodextrin ((iso)maltase and a-amylase); maltodextrin with a-1,6-branching (isomaltase, maltase and a-amylase) and maltose (maltase). When exceeding the animal’s capacity to enzymatically hydrolyse starch, fermentation occurs, leading to a reduced faecal dry matter (DM) content and pH. Forty calves (13 weeks of age) were assigned to either a lactose control diet or one of four titration strategies (n=8 per treatment), each testing the stepwise exchange of lactose for one SP. Dietary inclusion of each SP was increased weekly by 3% at the expense of lactose and faecal samples were collected from the rectum weekly to determine DM content and pH. The increase in SP inclusion was stopped when faecal DM content dropped below 10.6% (i.e. 75% of the average initial faecal DM content) for 3 consecutive weeks. For control calves, faecal DM content and pH did not change over time. For 87% of the SP-fed calves, faecal DM and pH decreased already at low inclusion levels, and linear regression provided a better fit of the data (faecal DM content or pH v. time) than non-linear regression. For all SP treatments, faecal DM content and pH decreased in time (P
|The effect of replacing lactose by glucose, fructose or glycerol in milk replacer on energy partitioning in Holstein-Friesian calves
Gilbert, M.S. ; Pantophlet, A.J. ; Borne, J.J.G.C. van den; Hendriks, W.H. ; Schols, H.A. ; Gerrits, W.J.J. - \ 2014
In: Proceedings of the 30th Biennial Conference of the Australian Society of Animal Production. - Australian Society of Animal Production - p. 113 - 113.
|The effect of replacing lactose by glucose, fructose or glycerol on the energy partitioning of milk-fed calves
Gilbert, M.S. ; Pantophlet, A.J. ; Borne, J.J.G.C. van den; Hendriks, W.H. ; Schols, H.A. ; Gerrits, W.J.J. - \ 2014
In: Proceedings of the Wias Science Day 30 April 2014. - Wageningen : Wias Science Day - p. 22 - 22.
Small intestinal fermentation contributes substantially to starch disappearance in milk-fed calves
Gilbert, M.S. ; Pantophlet, A.J. ; Borne, J.J.G.C. van den; Schols, H.A. ; Gerrits, W.J.J. - \ 2014
|Small intestinal fermentation contributes substantially to starch disappearance in milk-fed calves
Gilbert, M.S. ; Pantophlet, A.J. ; Borne, J.J.G.C. van den; Schols, H.A. ; Gerrits, W.J.J. - \ 2013
In: Proceedings of the 4th International Symposium on Energy and Protein Metabolism and Nutrition, 9-12 September 2013, Sacramento, California, USA. - Wageningen : Wageningen Academic Publishers - ISBN 9789086862276 - p. 59 - 60.
A titration approach to identify the capacity for starch digestion in milk-fed calves
Gilbert, M.S. ; Borne, J.J.G.C. van den; Pantophlet, A.J. ; Gerrits, W.J.J. - \ 2013
In: Proceedings of the 4th International Symposium on Energy and Protein Metabolism and Nutrition, 9-12 September 2013, Sacramento, California, USA. - Wageningen : Wageningen Academic Publishers - ISBN 9789086862276 - p. 233 - 234.
Calf milk replacers commonly contain 40-50% lactose. For economic reasons, starch is of interest as a lactose replacer. Compared with lactose, starch digestion is generally low in calves. Ileal disappearance of starch was only 60% in calves, whereas lactose disappeared for 97% (Coombe and Smith, 1974). This indicates that the activity of enzymes required for the hydrolysis of starch to glucose limits starch digestion in milk-fed calves. It is however unknown which enzyme system is limiting the rate of starch hydrolysis in the intestinal lumen of calves. In addition, a maximum may exist for the daily quantity of starch that can be hydrolyzed and absorbed. Potentially, enzyme systems may also adapt to the starch fed. Both may be subject to considerable inter-individual variation.