Characterization of a model of hindgut acidosis in mid-lactation cows: A pilot study.

The objective of this pilot study was to generate data to support the development of an experimental model of hindgut acidosis to further understand its systemic consequences independently of rumen acidosis. Four ruminally fistulated multiparous Holstein cows (213 ± 11 d in milk) were subjected to 2 consecutive experimental periods (P1 and P2), separated by a 3-d washout. Experimental periods were 96 h long from the baseline to the final measurements but expanded over 5 calendar days (d 0-4). Abomasal infusions of saline and corn starch (2.8 kg/d) were performed for the first 72 h (d 0-3) of P1 and P2, respectively. Final measurements were performed 24 h after the end of the infusions (d 4). Each cow was used as its own control by comparing P2 to P1. Postruminal-intestinal permeability was assessed by Cr appearance in blood after a pulse dose administration of Cr-EDTA into the abomasum on d 2 (48 h after infusion initiation) of each period. Starch infusion during P2 was associated with a milk protein yield increase (3.3%) and a decrease in milk urea nitrogen (11%). Fecal dry matter increased (8.8%), and starch content tended to increase (∼2 fold) during P2. There was a period-by-day interaction for fecal pH as it decreased during starch infusion (1.3 pH points) but remained constant during P1. Although fecal lactate was not detectable during P1, it consistently increased during starch infusion. Fecal alkaline phosphatase activity also increased (∼17 fold) in association with starch infusion. Two hours after Cr-EDTA administration, blood Cr concentration was higher during starch infusion, resulting in a tendency for a treatment-by-hour interaction. Furthermore, blood d-lactate increased (∼2.5 fold), serum Cu decreased (18%), and blood urea nitrogen, cholesterol, and Ca tended to decrease (9.4%, 1.2%, and 2.4%, respectively), relative to P1. The current results suggest that hindgut acidosis was successfully induced by postruminal starch infusion, leading to gut damage and increased intestinal permeability. However, indications of systemic inflammation were not observed. The herein described preliminary results will require confirmation in a properly powered study.

Digestive and metabolic efficiency of energy and nitrogen during lactation and the dry period in dairy cows.

The objective of this study was to characterize total-tract nutrient digestibility, energy balance, and N balance in the critical dietary and metabolic transitions of the lactation cycle. Twelve dairy cows were housed in tiestalls from 10 wk before to 16 wk after parturition. After 2 wk of adaptation to the facility and diet, digestibility of organic matter (OM), neutral detergent fiber (NDF), starch, and N were measured, and energy and N balances determined at weekly intervals by total collection of feces, urine, and milk over 48 h. Cows were individually fed ad libitum a grass silage- and corn silage-based total mixed ration during lactation and a corn silage- and barley straw-based total mixed ration during the dry period. Effects of stage of lactation were evaluated by clustering week in 5 groups: late lactation (wk -8 to -7), dry period (wk -6 to -1), and 3 early lactation periods (wk 1 to 5, wk 6 to 10, and wk 11 to 16). In lactation, apparent total-tract digestibility of OM, NDF, and starch was lowest in the first 5 wk of lactation. From wk 2 to 16 after parturition, apparent nutrient digestibility of all nutrients increased linearly, but with a negative quadratic component for dry matter, OM, and NDF, to levels comparable to those reported in last 2 wk of the previous lactation. However, differences in digestibility across lactation stage were moderate, illustrated by the difference between OM digestibility in late lactation (last 2 wk, 74.8%) and early lactation (first 5 wk, 72.5%). Cows were in negative energy balance for the first 8 wk after calving, and in negative N balance for the first 4 wk after calving. Based on energy and N balance, we predicted that 36.5 kg of body fat and 3.5 kg of body protein were gained in the last 8 wk before calving, and that 47.5 kg of body fat and 7.6 kg of body protein were mobilized in the first weeks of lactation. These predicted changes in body mass, both the gain before calving and loss after calving, were greater by 37% and 10%, respectively, than fluctuations in measured body weight (corrected for predicted gut fill and fetus weights). At wk 1 and 2 postpartum, body N loss corresponded to 25 and 29%, respectively, of total N excretion in milk, and body energy loss corresponded to 64% and 44%, respectively, of the energy exported to milk, illustrating the important contribution of N and energy from body stores to milk production in early lactation. Metabolic N efficiency, measured as total N output (milk and body) over digestible N input (from diet and body), averaged 54.4% in the last 2 wk of lactation, increased to 65.9% 2 wk after calving, and decreased linearly as lactation advanced to 61.9% by wk 16. Short (48 h) but weekly repetition of total collection of feces and urine appears to be a suitable approach to evaluate temporal changes in nutrient digestibility, energy balance, and N balance across lactation and the dry period.

Targeting the Hindgut to Improve Health and Performance in Cattle.

An adequate gastrointestinal barrier function is essential to preserve animal health and well-being. Suboptimal gut health results in the translocation of contents from the gastrointestinal lumen across the epithelium, inducing local and systemic inflammatory responses. Inflammation is characterized by high energetic and nutrient requirements, which diverts resources away from production. Further, barrier function defects and inflammation have been both associated with several metabolic diseases in dairy cattle and liver abscesses in feedlots. The gastrointestinal tract is sensitive to several factors intrinsic to the productive cycles of dairy and beef cattle. Among them, high grain diets, commonly fed to support lactation and growth, are potentially detrimental for rumen health due to their increased fermentability, representing the main risk factor for the development of acidosis. Furthermore, the increase in dietary starch associated with such rations frequently results in an increase in the bypass fraction reaching distal sections of the intestine. The effects of high grain diets in the hindgut are comparable to those in the rumen and, thus, hindgut acidosis likely plays a role in grain overload syndrome. However, the relative contribution of the hindgut to this syndrome remains unknown. Nutritional strategies designed to support hindgut health might represent an opportunity to sustain health and performance in bovines.

A Cross-Sectional Study of Obesity Effects on the Metabolomic Profile of a Leptin-Resistant Swine Model.

Identifying metabolite signatures associated with obesity and related diseases might represent a valuable preventive and therapeutic tool to predict subjects at risk, establish an accurate prognosis, and monitor treatment success. The current cross-sectional study is aimed to evaluate the metabolite profile of diet-induced obesity in a porcine model of leptin resistance. Six Iberian female pigs prone to develop obesity (OB) were ad libitum fed a fat-enriched diet (HFD) for 82 days. Five lean Iberian sows (CON) in a maintenance diet served as controls. At the end of the dietary treatments, all animals were sacrificed, and plasma, liver, and muscle samples were immediately collected for nuclear magnetic resonance analysis. In plasma, signals corresponding to betaine, glycerophosphocholine/phosphocholine, glycine, and glutamate were decreased; and the valine signal was increased in OB sows compared to controls. Similarly, the betaine signal was decreased in the liver. No differences were detected in muscle. The observed metabolite changes suggest alterations in branched chain amino-acid metabolism and the methionine-homocysteine cycle, which have been previously associated with obesity-related diseases and type 2 diabetes in human observational studies. The current study supports the utilization of the leptin resistant Iberian pig for further interventional research in the field.

Heat stress increases insulin sensitivity in pigs.

Proper insulin homeostasis appears critical for adapting to and surviving a heat load. Further, heat stress (HS) induces phenotypic changes in livestock that suggest an increase in insulin action. The current study objective was to evaluate the effects of HS on whole-body insulin sensitivity. Female pigs (57 ± 4 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 21°C) and were fed ad libitum. During period 2, pigs were exposed to: (i) constant HS conditions (32°C) and fed ad libitum (n = 6), or (ii) TN conditions and pair-fed (PFTN; n = 6) to eliminate the confounding effects of dissimilar feed intake. A hyperinsulinemic euglycemic clamp (HEC) was conducted on d3 of both periods; and skeletal muscle and adipose tissue biopsies were collected prior to and after an insulin tolerance test (ITT) on d5 of period 2. During the HEC, insulin infusion increased circulating insulin and decreased plasma C-peptide and nonesterified fatty acids, similarly between treatments. From period 1 to 2, the rate of glucose infusion in response to the HEC remained similar in HS pigs while it decreased (36%) in PFTN controls. Prior to the ITT, HS increased (41%) skeletal muscle insulin receptor substrate-1 protein abundance, but did not affect protein kinase B or their phosphorylated forms. In adipose tissue, HS did not alter any of the basal or stimulated measured insulin signaling markers. In summary, HS increases whole-body insulin-stimulated glucose uptake.

Heat Stress Alters Ovarian Insulin-Mediated Phosphatidylinositol-3 Kinase and Steroidogenic Signaling in Gilt Ovaries.

Heat stress (HS) compromises a variety of reproductive functions in several mammalian species. Inexplicably, HS animals are frequently hyperinsulinemic despite marked hyperthermia-induced hypophagia. Our objectives were to determine the effects of HS on insulin signaling and components essential to steroid biosynthesis in the pig ovary. Female pigs (35 ± 4 kg) were exposed to constant thermoneutral (20°C; 35%-50% humidity; n = 6) or HS conditions (35°C; 20%-35% humidity; n = 6) for either 7 (n = 10) or 35 days (n = 12). After 7 days, HS increased (P < 0.05) ovarian mRNA abundance of the insulin receptor (INSR), insulin receptor substrate 1 (IRS1), protein kinase B subunit 1 (AKT1), low-density lipoprotein receptor (LDLR), luteinizing hormone receptor (LHCGR), and aromatase (CYP19a). After 35 days, HS increased INSR, IRS1, AKT1, LDLR, LHCGR, CYP19a, and steroidogenic acute regulatory protein (STAR) ovarian mRNA abundance. In addition, after 35 days, HS increased ovarian phosphorylated IRS1 (pIRS1), phosphorylated AKT (pAKT), STAR, and CYP19a protein abundance. Immunostaining analysis revealed similar localization of INSR and pAKT1 in the cytoplasmic membrane and oocyte cytoplasm, respectively, of all stage follicles, and in theca and granulosa cells. Collectively, these results demonstrate that HS alters ovarian insulin-mediated PI3K signaling pathway members, which likely impacts follicle activation and viability. In summary, environmentally induced HS is an endocrine-disrupting exposure that modifies ovarian physiology and potentially compromises production of ovarian hormones essential for fertility and pregnancy maintenance.

Effects of dairy products on intestinal integrity in heat-stressed pigs.

Heat stress compromises intestinal integrity which may partially explain its negative effects on animal health and productivity. Research suggests that challenged intestinal barrier function improves with dietary dairy products in various models. Thus, the study objective was to evaluate the effects of bovine milk whey protein (WP) and colostral whey protein (CWP) on intestinal integrity in heat-stressed pigs. Crossbred gilts (39 ± 3 kg body weight) were fed 1 of 4 diets (n = 8 pigs/diet): control (Ct), control diet containing an 80% WP and 20% CWP product (WP80), control diet containing a 98% WP and 2% CWP product (WP98), and control diet containing a 100% WP product (WP100). After 7d on experimental diets, pigs were exposed to constant heat stress conditions (32 °C) for 24h. There were no treatment differences in growth or body temperature indices prior to heat stress. During heat exposure, both rectal temperature and respiration rate increased (+0.85 °C and 3-fold, respectively; P < 0.01), and feed intake and body weight decreased (44% and -0.5kg, respectively; P < 0.01), but neither variable was affected by dietary treatments. Plasma L-lactate and D-lactate concentrations increased (36%; P < 0.01) and tended to increase (19%; P = 0.09) with heat stress. After 24h of heat exposure, WP100-fed pigs had lower plasma D-lactate relative to Ct-fed pigs. Ileal transepithelial electrical resistance was decreased (37%; P = 0.02) in WP80 pigs, compared with controls. No differences were detected in other intestinal integrity ex vivo measurements. These data demonstrate that dietary WP and CWP did not mitigate intestinal integrity dysfunction during severe heat stress.

Effects of mammalian in utero heat stress on adolescent body temperature.

In utero hyperthermia can cause a variety of developmental issues, but how it alters mammalian body temperature during adolescence is not well-understood. Study objectives were to determine the extent to which in utero hyperthermia affects future phenotypic responses to a heat load. Pregnant first parity pigs were exposed to thermal neutral (TN) or heat stress (HS) conditions during the entire gestation. Of the resultant offspring, 12 were housed in TN conditions, and 12 were maintained in HS conditions for 15 days. Adolescent pigs in HS conditions had increased rectal temperature and respiration rate (RR) compared to TN pigs, regardless of gestational treatment. Within the HS environment, no gestational difference in RR was detected; however, GHS pigs had increased rectal temperature compared to GTN pigs. As rectal temperature increased, GTN pigs had a more rapid increase in RR compared to the GHS pigs. Adolescent HS decreased nutrient intake, and body weight gain, but neither variable was statistically influenced by gestational treatments. In summary, in utero HS compromises the future thermoregulatory response to a thermal insult.