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.

Prepartum and postpartum nutritional management to optimize fertility in high-yielding dairy cows in confined TMR systems

“…Other research groups (Rukkwamsuk et al, 1998;Holcomb et al, 2001;Holtenius et al, 2003;Vickers et al, 2013) have reached similar conclusions about controlling energy intake during the dry period, although not all studies have shown benefits (Winkleman et al, 2008). Application of these principles can be through controlled limit-feeding of moderate energy diets or ad libitum feeding of high-bulk, low-energy rations (Janovick and Drackley, 2010;Janovick et al, 2011;Ji et al, 2012) as proposed by others (Beever, 2006).Effects of controlling prepartum energy intake on fertility Individual studies such as these lack statistical power to accurately determine effects of diet on milk production, disease incidence and reproductive success. Therefore, Cardoso et al (2013) conducted a pooled statistical analysis of seven studies (cow was the experimental unit) at the University of Illinois to investigate associations between prepartum energy feeding regimen and reproductive performance.…”

“…Manage pre-calving energy intake Our research group has shown that controlling energy intake during the dry period to near calculated requirements leads to better transition success (Grum et al, 1996;Dann et al, 2005 andDouglas et al, 2006;Janovick et al, 2011;Graugnard et al, 2012 andJi et al, 2012). Our research drew from earlier reports that limiting nutrient intakes to requirements of the cows was preferable to overconsumption of energy (e.g.…”

“…The simplest and most easily defended principle of nutrition for dairy cows during the dry period and transition is to feed to meet but not greatly exceed requirements (Drackley and Dann, 2008). Although not new, this concept has been incorporated into practical systems suitable for modern dairy management practices on both small and large dairies.Transition nutritional management in TMR-fed herds 9 Manage pre-calving energy intake Our research group has shown that controlling energy intake during the dry period to near calculated requirements leads to better transition success (Grum et al, 1996;Dann et al, 2005 and Douglas et al, 2006;Janovick et al, 2011;Graugnard et al, 2012 andJi et al, 2012). Our research drew from earlier reports that limiting nutrient intakes to requirements of the cows was preferable to overconsumption of energy (e.g.…”

“…Alterations in cellular and gene-level responses in liver (Loor et al, 2006 and and adipose tissue (Ji et al, 2012) potentially explain many of the changes at cow level. Over-consumption of energy during the close-up period increases the enzymatic 'machinery' in adipose tissue for TAG mobilization after calving, with transcriptional changes leading to decreased lipogenesis, increased lipolysis and decreased ability of insulin to inhibit lipolysis (Ji et al, 2012). Controlling energy intake during the dry period also improved neutrophil function postpartum (Graugnard et al, 2012) and so may lead to better immune function.…”

“…Over-consuming energy results in negative responses of metabolic indicators, such as higher NEFA and BHBA in blood and more TAG in the liver after calving (Douglas et al, 2006;Janovick et al, 2011). Alterations in cellular and gene-level responses in liver (Loor et al, 2006 and and adipose tissue (Ji et al, 2012) potentially explain many of the changes at cow level. Over-consumption of energy during the close-up period increases the enzymatic 'machinery' in adipose tissue for TAG mobilization after calving, with transcriptional changes leading to decreased lipogenesis, increased lipolysis and decreased ability of insulin to inhibit lipolysis (Ji et al, 2012).…”