title: Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity.
abstract: Hepatic metabolic gene networks were studied in dairy cattle fed control (CON, 1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the last 45 days of pregnancy. A total of 57 target genes encompassing PPARα-targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on -14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more negative energy balance (NEB) postpartum and had greater serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG) concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded to postpartal NEB by up-regulating expression of PPARα-targets in the fatty acid oxidation and ketogenesis pathways, along with gluconeogenic genes. Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4)) and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin, and greater lipogenic gene expression suggesting insulin sensitivity was not impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal responses in NEFA and FGF21 with OVE support a role of this hepatokine in diminishing adipose insulin sensitivity.
authors.affiliation: Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA. ; Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: M Jawad
authors.initials: MJ
authors.lastname: Khan
authors.affiliation: NUPEEC, Departamento de Clínicas Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brasil.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Jacometo
authors.affiliation: Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Graugnard
authors.affiliation: NUPEEC, Departamento de Clínicas Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brasil.
authors.forename: Marcio N
authors.initials: MN
authors.lastname: Corrêa
authors.affiliation: Embrapa Rondônia, Porto Velho, RO, Brasil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Schmitt
authors.affiliation: Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardoso
authors.affiliation: Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Loor
keywords: lactation; nuclear receptor; nutrition; obesity
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