Effects of the periparturient period and parity on local innervation markers in subcutaneous adipose tissue of dairy cows.

Adipose tissue serves as a vital energy source to meet the metabolic demands of the periparturient period in dairy cows. However, excessive release of nonesterified fatty acids (NEFA) from adipose tissue can lead to postpartum metabolic diseases. The objectives of this investigation were to identify changes in expression of nervous system gene and protein markers in the adipose tissue of dairy cows at varying parities during the periparturient period and to define their associations with circulating markers of metabolism and inflammation. Tailhead subcutaneous adipose tissue (SAT) was collected from 16 multiparous Holstein dairy cows (3.5 ± 1.6 lactations, 15,136 ± 1,743 previous 305-d milk yield, mean ± SD) approximately 10 d before parturition (8.56 ± 2.3 d to parturition, mean ± SD) and at 10 d postpartum. Blood samples were collected concurrently with SAT biopsy at prepartum time point and again, separately, at 7 d postpartum. Blood metabolites and inflammatory markers were quantified, and SAT was analyzed for markers related to nervous system signaling. Differences were assessed using a repeated-measures mixed-effects model in PROC MIXED in SAS (version 9.4; SAS Institute Inc., Cary, NC). Period was treated as a repetition by cow nested in parity, and parity, period, and the interaction of parity and period served as fixed effects. Metabolic profiling was consistent with that of transition dairy cows, with elevated NEFA and BHB and decreased insulin concentrations in the postpartum period. Approximately 56% of the cows demonstrated elevated lipolysis (EL) in the postpartum period, and 44% of animals developed disease in the first 7 DIM. The expression of catecholamine biosynthesis markers tyrosine hydroxylase (TH), phosphorylated TH serine 40 residue (pTHser40), dopamine β-hydroxylase (DBH), and norepinephrine transporter (NET) did not change in SAT from the prepartum to postpartum period, suggesting a stable catecholamine biosynthesis machinery during the periparturient period. However, protein abundance of TH, pTHSer40, protein gene product 9.5, NET, nerve growth factor receptor (intracellular domain 25 kDa), and glial fibrillary acidic protein increased with parity. Interestingly, DBH, the enzyme that converts dopamine to norepinephrine, decreased abundance with parity, suggesting reduced local capacity for norepinephrine synthesis in the SAT of older cows. Concurrently, increased expression of NET may reflect altered sympathetic signaling dynamics in SAT with advancing parity. The sensory system marker, calcitonin gene-related peptide, was detectable in SAT but did not differ across the periparturient period and was more abundant in cows in the third lactation. These findings indicate that advancing parity is associated with expansion and reorganization of local SAT innervation rather than acute periparturient remodeling. Markers of lipogenesis and lipolysis regulation but not of adipose tissue beiging were altered between the prepartum and postpartum periods, suggesting that neural remodeling may shape local SAT metabolic adaptation rather than adipocyte fate. Overall, our results reveal a previously underappreciated role of parity in shaping neural-catecholamine regulation of SAT during the periparturient period, providing new insights into mechanisms that may influence adipose tissue dysfunction and subsequent susceptibility to develop metabolic disorders in multiparous dairy cows.