title: Overfeeding a moderate energy diet prepartum does not impair bovine subcutaneous adipose tissue insulin signal transduction and induces marked changes in peripartal gene network expression.
abstract: Mechanisms regulating subcutaneous adipose tissue (SAT) insulin sensitivity and gene network expression during the peripartal period were evaluated in cows fed to meet or exceed prepartal energy requirements. Holstein cows were dried off at -50 d relative to expected parturition and fed a controlled-energy diet [CON; net energy for lactation=1.24 Mcal/kg of dry matter (DM); 36% of DM as wheat straw] until -21 d. Cows were then randomly assigned (n=7/diet) to either the same CON diet or a moderate-energy close-up diet (OVE; net energy for lactation=1.47 Mcal/kg of DM) until parturition. Biopsies of SAT were harvested at -10, 7, and 21 d for mRNA expression of 48 genes associated with insulin signaling, adipogenesis, and lipolysis. In vitro basal and insulin-stimulated insulin receptor substrate 1 tyrosine phosphorylation (IRS1-PY) was assessed at -10 and 7 d. The OVE led to more positive energy balance and greater serum insulin concentration prepartum. Compared with CON, OVE led to a more drastic increase in serum NEFA and also greater overall serum BHBA postcalving, both of which were associated with greater hepatic total lipid and triacylglycerol concentration. Close-up OVE did not improve any aspect of performance. In prepartal SAT, insulin-stimulated IRS1-PY was greater in OVE than in CON. However, IRS1-PY, serum insulin, and GLUT4 expression decreased postpartum regardless of prepartal treatment, suggesting a more severe state of insulin resistance. The expression of all genes encoding adipogenic regulators (PPARG and ZFP423), most lipogenic enzymes/inducers (FASN, SCD, DGAT2, and INSIG1), and basal-lipolysis regulators (ATGL and ABDH5) was greater at -10 d in OVE than in CON. Whereas adipogenic and basal lipolysis regulator expression remained greater in cows fed OVE by 7 d postpartum, expression of all lipogenic enzymes decreased regardless of diet. Despite those responses, the approximately 3-fold increase in expression of IRS1 and ZFP423 between 7 and 21 d suggested that insulin responsiveness and adipogenic capacity of SAT were partially restored. Expression of the preadipocyte marker DLK1, adiponutrin (PNPLA3), and fibroblast growth factor 21 (FGF21) was undetectable. Results suggested that close-up energy overfeeding did not exacerbate insulin resistance in SAT. Signs of restored insulin responsiveness (upregulation of IRS1, INSIG2, SREBF1, and ZFP423) were apparent as early as 3 wk postpartum. Thus, identifying specific nutrients capable of activating PPARγ after calving in AT might help accelerate its replenishment. A regulatory network encompassing the genes and physiological measurements obtained is proposed.
authors: Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
authors: P
authors: P
authors: Ji
authors: J S
authors: JS
authors: Osorio
authors: J K
authors: JK
authors: Drackley
authors: J J
authors: JJ
authors: Loor
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics / Q000378:metabolism*; D002149:Energy Intake / Q000502:physiology*; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling / Q000662:veterinary; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D044343:Overnutrition / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma; D014157:Transcription Factors; D012313:RNA; D064429:Fatty Acid Synthases