👤 Daniel E Graugnard

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. Show less

Adipocyte differentiation is probably controlled by transcriptional and post-transcriptional regulation. Longissimus lumborum from Angus steers (aged 155 d; seven animals per diet) fed high-starch or low-starch diets for 112 d (growing phase) followed by a common high-starch diet for an additional 112 d (finishing phase) was biopsied at 0, 56, 112 and 224 d for transcript profiling via quantitative PCR of twenty genes associated with adipogenesis and energy metabolism. At 56 d steers fed high starch had greater expression of PPARgamma as well as the lipogenic enzymes ATP citrate lyase (ACLY), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD), glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), and diacylglycerol O-acyltransferase homologue 2 (DGAT2), and the adipokine adiponectin (ADIPOQ). Expression of insulin-induced gene 1 (INSIG1) was also greater with high starch at 56 d. Steers fed low starch experienced a marked increase in FASN, FABP4, SCD, DGAT2 and thyroid hormone-responsive (SPOT14 homologue, rat) (THRSP) between 56 and 112 d of feeding. A greater expression of the transcription factors sterol regulatory element-binding transcription factor 1 (SREBF1) and MLX interacting protein-like (MLXIPL) was observed at 224 d in steers fed high starch, suggesting a nutritional imprinting effect. Carryover effects of low starch feeding were discerned by greater expression at 224 d of THRSP, FABP4, SCD and DGAT2. These steers also had greater PPARgamma at 224 d. Despite these responses, low starch led to greater expression at 224 d of nuclear receptor subfamily 2, group F, member 2 (NR2F2), a known repressor of rodent adipocyte differentiation through its negative effects on PPARgamma, ADIPOQ and FABP4. Results suggested that early exposure to high starch induced precocious intramuscular adipocyte proliferation and metabolic imprinting of lipogenic transcription regulators. Low starch might have blunted the PPARgamma-driven adipogenic response through up-regulation of NR2F2 but the endogenous ligand for this nuclear receptor remains unknown. Show less