title: Insulin signaling and skeletal muscle atrophy and autophagy in transition dairy cows either overfed energy or fed a controlled energy diet prepartum.
abstract: During periods of negative energy balance, mobilization of muscle is a physiologic process providing energy and amino acids. This is important in transition dairy cows experiencing negative energy and protein balance postpartum. Overconsumption of energy during late pregnancy affects resting glucose and insulin concentrations peripartum and increases the risk for hyperketonemia postpartum, but the effects on muscle tissue are not fully understood. Skeletal muscle accounts for the majority of insulin-dependent glucose utilization in ruminants. Our objective was to study peripartal skeletal muscle insulin signaling as well as muscle accretion and atrophy in cows with excess energy consumption prepartum. Skeletal muscle biopsies were obtained 28 and 10 days prepartum, as well as 4 and 21 days postpartum from 24 Holstein cows. Biopsies were taken immediately before and 60 min after intravenous glucose challenge causing endogenous release of insulin. Gene expression of IGF-1, myostatin, and atrogin-1, as well as immunoblot analysis of atrogin-1, muRF1, ubiquitinated proteins, LC3, and phosphorylation of AKT, ERK and mTORC1 substrate 4EBP1 was performed. Excess energy consumption in late pregnancy did not lead to changes in insulin-dependent molecular regulation of muscle accretion or atrophy compared with the controlled energy group. In both groups, phosphorylation of AKT and mTORC1 substrate was significantly decreased postpartum whereas proteasome activity and macroautopagy were upregulated. This study showed that in addition to the proteasome pathway of muscle atrophy, macroautophagy is upregulated in postpartum negative energy and protein balance regardless of dietary energy strategy prepartum and was higher in cows overfed energy throughout the study period.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, Cornell College of Veterinary Medicine, Ithaca, NY, 14853-6401, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mann
authors.affiliation: Department of Animal Pathology, College of Veterinary Medicine, Universidade de Santiago de Compostela, 27002, Lugo, Spain.|Graham Centre for Agricultural Innovation, School of Animal and Veterinary Sciences, Charles Sturt University and NSW Department of Primary Industries, Wagga Wagga, NSW, 2678, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Abuelo
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, Cornell College of Veterinary Medicine, Ithaca, NY, 14853-6401, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: Nydam
authors.affiliation: Department of Animal Science, Cornell College of Veterinary Medicine, Ithaca, NY, 14853-6401, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Leal Yepes
authors.affiliation: Department of Animal Science, Cornell College of Veterinary Medicine, Ithaca, NY, 14853-6401, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Overton
authors.affiliation: Department of Clinical Sciences, Cornell College of Veterinary Medicine, Ithaca, NY, 14853-6401, USA. jw37@cornell.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Wakshlag
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002417:Cattle; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin / Q000235:genetics / Q000378:metabolism; D049590:Postpartum Period; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D055435:Myostatin; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt
keywords: Dairy cow; Insulin pathway; Ketosis; Muscle; Muscle atrophy; Negative energy balance