scholarly journals Hepatic metabolomics and transcriptomics to study susceptibility to ketosis in response to prepartal nutritional management

Author(s):  
Khuram Shahzad ◽  
Vincenzo Lopreiato ◽  
Yusheng Liang ◽  
Erminio Trevisi ◽  
Johan S. Osorio ◽  
...  

Abstract Background Ketosis in dairy cows is associated with body fat mobilization during the peripartal period. Sub-clinical and clinical ketosis arise more frequently in cows that are overfed energy during the entire dry (last 50 to 45 days prior to parturition) or close-up period (last ~ 28 days prepartum). Methods A retrospective analysis was performed on 12 cows from a larger cohort that were fed a higher-energy diet [1.54 Mcal/kg of dry matter (DM); 35.9% of DM corn silage and 13% of DM ground corn] during the close-up dry period, of which 6 did not develop clinical ketosis (OVE, 0.83 mmol/L plasma hydroxybutyrate; BHB) and 6 were diagnosed with clinical ketosis (KET, 1.4 mmol/L BHB) during the first week postpartum. A whole-transcriptome bovine microarray (Agilent Technologies) and metabolomics (GC-MS, LC-MS; Metabolon® Inc.) were used to perform transcript and metabolite profiling of liver tissue harvested at − 10 days relative to parturition which allowed to establish potential associations between prepartal transcriptome/metabolome profiles and susceptibility to clinical ketosis postpartum. Results Cows in KET had greater (P = 0.01) overall body weight between − 2 and 1 week around parturition, but similar body condition score than OVE. Although dry matter intake (DMI) did not differ prepartum, KET cows had lower (P < 0.01) DMI and similar milk yield as OVE cows during the first week postpartum. Transcriptome analysis revealed a total of 3065 differentially expressed genes (DEG; P ≤ 0.05) in KET. Metabolomics identified 15 out of 313 total biochemical compounds significantly affected (P ≤ 0.10) in KET. Among those, greater concentrations (P ≤ 0.06, + 2.3-fold) of glycochenodeoxycholate in KET cows also have been detected in humans developing non-alcoholic fatty liver disease. Bioinformatics analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and the DEG revealed that, among the top 20 most-impacted metabolic pathway categories in KET, 65% were overall downregulated. Those included ‘Metabolism of cofactors and vitamins’, ‘Biosynthesis of other secondary metabolites’, ‘Lipid’, ‘Carbohydrate’, and ‘Glycan biosynthesis and metabolism’. The lower relative concentration of glucose-6-phosphate and marked downregulation of fructose-1,6-bisphosphatase 2 and pyruvate dehydrogenase kinase 4 support a strong impairment in gluconeogenesis in prepartal liver of cows developing KET postpartum. Among the top 20 most-impacted non-metabolic pathways, 85% were downregulated. Pathways such as ‘mTOR signalling’ and ‘Insulin signalling’ were among those. ‘Ribosome’, ‘Nucleotide excision repair’, and ‘Adherens junctions’ were the only upregulated pathways in cows with KET. Conclusions The combined data analyses revealed more extensive alterations of the prepartal liver transcriptome than metabolome in cows overfed energy and developing ketosis postpartum. The causative link between these tissue-level adaptations and onset of clinical ketosis needs to be studied further.

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 192-192
Author(s):  
Alice Brandão ◽  
Reinaldo F Cooke ◽  
Kelsey Schubach ◽  
Bruna Rett ◽  
Osvaldo Souza ◽  
...  

Abstract This experiment compared performance and physiological responses of the offspring from cows supplemented with Ca salts of soybean oil (CSSO) or prilled saturated fat (CON) during late gestation. Non-lactating, pregnant Angus × Hereford cows (n = 104) that conceived during the same fixed-time artificial insemination protocol, using semen from 2 sires, were used in this experiment. Cows were ranked by pregnancy sire, body weight (BW), and body condition score (BCS). On d 180 of gestation (d -15), cows were randomly assigned to receive (dry matter basis) 415 g of soybean meal per cow daily in addition to 1) 195 g/cow daily of CSSO (n = 52) or 2) 170 g/cow daily of CON (n = 52). Cows were maintained in 2 pastures (26 cows/treatment per pasture), and received daily 12.7 kg/cow (dry matter basis) of grass-alfalfa hay. From d 0 until calving, cows were segregated into 1 of 24 feeding pens thrice weekly and received treatments individually. Cow BW and BCS were recorded, and blood samples were collected on d -15 of the experiment and within 12 h after calving. Calf BW was also recorded and blood sample collected within 12 h of calving. Calves were weaned on d 290 of the experiment, preconditioned for 35 d (d 291 to 325), and transferred to a feedyard where they remained until slaughter. Upon calving, CSSO cows and calves had greater (P &lt; 0.01) plasma concentrations of linoleic acid and total ω - 6 FA compared with CON cohorts. No differences in calf birth BW, weaning BW, and final preconditioning BW were noted (P ≥ 0.36) between treatments. Average daily gain and final BW in the feedlot were greater (P ≤ 0.05) in steers from CSSO cows compared with CON. The incidence of calves diagnosed with BRD that required a second antimicrobial treatment was less (P = 0.03) in calves from CSSO cows, resulting in reduced (P = 0.05) need of treatments to regain health compared with CON (Table 5). Upon slaughter, longissimus muscle area was greater (P = 0.03) in calves from CSSO cows compared with CON. Collectively, these results suggest that supplementing CSSO to late-gestating beef cows stimulated programming effects on postnatal offspring growth and Page 2 of 15 For Peer Review health. Therefore, supplementing late-gestating beef cows with CSSO appears to optimize offspring welfare and productivity in beef production systems.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 919
Author(s):  
Verónica M. Merino ◽  
Lorena Leichtle ◽  
Oscar A. Balocchi ◽  
Francisco Lanuza ◽  
Julián Parga ◽  
...  

The aim was to determine the effect of the herbage allowance (HA) and supplement type (ST) on dry matter intake (DMI), milk production and composition, grazing behavior, rumen function, and blood metabolites of grazing dairy cows in the spring season. Experiment I: 64 Holstein Friesian dairy cows were distributed in a factorial design that tested two levels of daily HA (20 and 30 kg of dry matter (DM) per cow) and two ST (high moisture maize (HMM) and cracked wheat (CW)) distributed in two daily rations (3.5 kg DM/cow/day). Experiment II: four mid-lactation rumen cannulated cows, supplemented with either HMM or CW and managed with the two HAs, were distributed in a Latin square design of 4 × 4, for four 14-d periods to assess ruminal fermentation parameters. HA had no effect on milk production (averaging 23.6 kg/day) or milk fat and protein production (823 g/day and 800 g/day, respectively). Cows supplemented with CW had greater protein concentration (+1.2 g/kg). Herbage DMI averaged 14.17 kg DM/cow.day and total DMI averaged 17.67 kg DM/cow.day and did not differ between treatments. Grazing behavior activities (grazing, rumination, and idling times) and body condition score (BCS) were not affected by HA or ST. Milk and plasma urea concentration increased under the high HA (+0.68 mmol/L and +0.90 mmol/L, respectively). Cows supplemented with HMM had lower milk and plasma urea concentrations (0.72 mmol/L and 0.76 mmol/L less, respectively) and tended (p = 0.054) to have higher plasma β-hydroxybutyrate. Ruminal parameters did not differ between treatments.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Brigitta Wichert ◽  
Julia Trossen ◽  
Daniel Uebelhart ◽  
Marcel Wanner ◽  
Sonja Hartnack

Obesity is a common problem in cats. In the experimental cat family of the institute of animal nutrition besides a “normal” lean phenotype, cats with predisposition to an overweight phenotype are present. To investigate energy requirements and food intake behaviour of intact male cats of different phenotypes, six “normal” lean cats (GL) and six cats disposed to overweight (GO) were used. At the beginning of the experiment, all cats had an ideal body condition score of 5. To reach this the GO cats had to pass a weight-loss program. Energy requirements of the cats were determined using respiration chambers, whereas the amount and frequency of food intake was measured with a feeding station recording the data automatically. Energy requirement at weight constancy of the GO cats was even on fat-free mass (FFM) significantly (P=0.02) lower (162.6 kJ/kg FFM/d) than that of the “normal” lean cats (246 kJ/kg FFM/d). The GO cats also showed a higher food intake34.5±1.5 g dry matter/kg body weight0.67compared to the GL cats (24.0±2.1 g dry matter/kg body weight0.67)(P=0.001). In conclusion quantifiable differences in food intake and behaviour in cats predisposed to overweight compared to “normal” lean cats were found.


2013 ◽  
Vol 125 (11) ◽  
pp. 501-511 ◽  
Author(s):  
Valérie Lebrun ◽  
Olivier Molendi-Coste ◽  
Nicolas Lanthier ◽  
Christine Sempoux ◽  
Patrice D. Cani ◽  
...  

Alcohol consumption is a major cause of liver disease. It also associates with increased cardiovascular risk and Type 2 diabetes. ALD (alcoholic liver disease) and NAFLD (non-alcoholic fatty liver disease) share pathological features, pathogenic mechanisms and pattern of disease progression. In NAFLD, steatosis, lipotoxicity and liver inflammation participate to hepatic insulin resistance. The aim of the present study was to verify the effect of alcohol on hepatic insulin sensitivity and to evaluate the role of alcohol-induced steatosis and inflammation on glucose homoeostasis. C57BL/6J mice were fed for 20 days a modified Lieber–DeCarli diet in which the alcohol concentration was gradually increased up to 35% of daily caloric intake. OH (alcohol liquid diet)-fed mice had liver steatosis and inflammatory infiltration. In addition, these mice developed insulin resistance in the liver, but not in muscles, as demonstrated by euglycaemic–hyperinsulinaemic clamp and analysis of the insulin signalling cascade. Treatment with the PPAR-α (peroxisome-proliferator-activated receptor-α) agonist Wy14,643 protected against OH-induced steatosis and KC (Kupffer cell) activation and almost abolished OH-induced insulin resistance. As KC activation may modulate insulin sensitivity, we repeated the clamp studies in mice depleted in KC to decipher the role of macrophages. Depletion of KC using liposomes-encapsuled clodronate in OH-fed mice failed both to improve hepatic steatosis and to restore insulin sensitivity as assessed by clamp. Our study shows that chronic alcohol consumption induces steatosis, KC activation and hepatic insulin resistance in mice. PPAR-α agonist treatment that prevents steatosis and dampens hepatic inflammation also prevents alcohol-induced hepatic insulin resistance. However, KC depletion has little impact on OH-induced metabolic disturbances.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 467-468
Author(s):  
Fernanda F Santos ◽  
Luciano Brochine ◽  
Vanderlei Benetel Junior ◽  
Maria Laura R Coelho ◽  
Augusto H Gameiro ◽  
...  

Abstract The objective of this study was to evaluate the milk production, body weight, and body condition score (BCS) of ewes fed with different energy levels. Seventy-one ewes were used and distributed in three treatments according to the metabolizable energy (ME, Mcal/kg) levels in the diet: CTL = according to the NRC (2007) recommendation for each stage (gestation and lactation); PLUS = CTL plus 10% of ME per kilogram of dry matter; LESS = CTL less 10% ME per kilogram of dry matter. Body weight and body condition score were evaluated a week before the expected date of parturition, a week after giving birth, and at weaning (60 days). Dairy production was evaluated at 20, 30, 40, 50 and 60 days after giving birth by the indirect method of the two weighing. The experimental design was analyzed as randomized complete blocks. There were no differences on milk production during almost all the lactation curve. Only on day 50 (P = 0.051), CTL was still at peak, while LESS and PLUS had already decreased their production. However, at 60 days, all treatments were already with low production, justifying weaning in this period. Results of weight and BCS showed a significant difference in all periods evaluates. Ewes in the PLUS diet had greater BW and BCS. The BCS before giving birth is expected to be over 3.5 and treatment LESS was the only one that did not achieve this score (2.66, 3.37, 3.83 for LESS, CTL, and PLUS, respectively). At weaning, ewes fed PLUS and CTL had BCS of 3.51 and 2.92, respectively, but treatment LESS had only 1.82. That is prejudicial for the next mating seasonal and this animal. We concluded that LESS diet interfered with the body reserves of sheep.


2020 ◽  
Vol 21 (23) ◽  
pp. 9091
Author(s):  
Valentina Ceccarelli ◽  
Ilaria Barchetta ◽  
Flavia Agata Cimini ◽  
Laura Bertoccini ◽  
Caterina Chiappetta ◽  
...  

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes’ size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02–1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76–1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.


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