The Effect of Prepartum Adiposity and Lipolysis on Gestational and Postnatal Oxylipids Biosynthesis

Gestational diabetes is associated with increased lipolysis and adipose tissue (AT) inflammation, which impair insulin signaling during the second half of pregnancy and in early lactation. Prevalence of gestational diabetes is high in overweight and obese women; similarly, dairy cows with high adiposity exhibit a surge in AT lipolysis and inflammatory responses during the last trimester of gestation that lead to AT insulin resistance. Oxidized FA (oxylipids) can modulate inflammatory responses during lipolysis. Linoleic acid (LNA) and arachidonic acid (AA) derived oxylipids, including hydroxy‐octadecadienoic acids (HODE), oxo‐octadecadienoic acids (oxoODE), and hydroxy‐eicosatetraenoic acids (HETE), were recently identified as potential biomarkers for early detection of insulin resistance. However, the effects of adiposity and lipolysis rate during late gestation and early lactation on oxylipid biosynthesis including FA substrate availability is currently unknown. We hypothesized that periparturient profiles of serum and AT concentrations of PUFA and oxylipids are dependent on body adiposity and lipolytic rate. Blood and subcutaneous AT samples were collected from multiparous Holstein cows with high (HA; n=5) or low (LA; n=4) adiposity scores at −27±7 (FO) and −10±5 (CU) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC‐MS/MS. We report that circulating free FA (FFA) concentrations increased as parturition approached, and peaked at PP. Across time, HA increased the concentration of circulating FFA compared to LA, reflecting a significant effect of adiposity on lipolytic rate during the periparturient period. Serum concentrations of AA and eicosapentanoic acid (EPA) were decreased at CU, compared to the other timepoints for all cows. Across time, serum AA and docosahexanoic acid (DHA) concentrations were decreased in HA compared to LA. AT content of AA and DHA, as well as LNA content in AT and serum, were unchanged throughout the study and were not influenced by adiposity. There were effects of both adiposity and timepoint on oxylipid concentrations. In AT, 13‐HODE, 5‐HETE, and 11‐HETE were increased at PP compared to FO and CU. Compared to LA, HA had decreased AT concentrations of 9‐HODE,13‐HODE, 5‐HETE, and 15‐HETE. Serum concentration of 9‐oxoODE was increased at PP and was positively correlated with serum FFA concentration ( r =0.52. P= 0.01), but was unaffected by adiposity. These data demonstrate that prepartum adiposity may limit the availability of serum PUFA, such as DHA, which serve as substrates for anti‐inflammatory oxylipids. Furthermore, lipolysis during late gestation and the onset of lactation may enhance AT biosynthesis and systemic release of HODE and HETE into circulation. Support or Funding Information USDA‐NIFA grants 2014‐68004‐21972 and 2015‐67015‐23207 Michigan Alliance for Animal Agriculture 1 Effect of adiposity and sampling time point across late gestation and early lactation on fatty add composition and oxylipid profile of subcutaneous adipose tissue and serum (mean + SEM) of dairy cows.AdipositySamplingMetabolite Low (LA) High (HA) SEM P Far off (FO) Close‐up (CU) Postpartum (PP) SEM PSerum free fatty acids (FFA) mEq/L FFA 0.43 0.63 0.05 <0.01 0.27 a 0.34 b 0.98 c 0.06 <0.01Serum fatty acids μmol/L Linoleic 341.5 222.6 78.8 NS 205.2 187 454 81.8 NS Arachidonic 42.2 20 10.5 0.02 22.2 a 17.4 a 53.8 b 16.1 0.01 EPA 2.5 0.9 0.8 NS 0.7 a 0.5 a 2.7 b 0.4 0.01 DHA 0.8 0.4 0.1 0.03 0.7 0.4 0.7 0.2 NSAdipose tissue fatty acids μmol/mg Linoleic acid 1340 1110 360 NS 1570 420 1720 500 NS Arachidonic acid 43.5 46.2 17 NS 43.9 9.3 52.4 16 NS EPA 0.83 0.43 0.3 NS 0.9 0.14 1.12 0.4 NS DHA 0.17 0.24 0.1 NS 0.23 0.31 0.07 0.2 NSAdipose tissue oxylipids nM/mg 9‐HODE 1.52 0.63 0.63 0.01 0.59 0.67 1.9 0.5 NS 9‐oxoODE 0.97 0.62 0.35 NS 0.49 1.01 0.87 0.26 NS 13‐HODE 2.42 0.71 0.84 0.05 0.77 a 0.95 a 2.97 b 0.7 0.05 13‐oxoODE 0.62 0.62 0.47 NS 0.32 0.5 1.09 0.38 NS 5‐HETE 0.6 0.33 0.12 0.05 0.24 a 0.56 b 0.6 b 0.12 0.05 11‐HETE 0.16 0.09 0.04 0.03 0.1 a 0.08 a 0.2 b 0.04 0.04 15‐HETE 0.29 0.04 0.08 0.01 0.06 a 0.12 b 0.42 c 0.08 0.01 20‐HETE 0.007 0.007 0.01 NS 0.007 0.007 0.006 0.004 NSSerum oxylipids nM/mL 9‐HODE 140.47 141.5 68.44 NS 210.98 111.45 101.65 60.4 NS 9‐oxoODE 82.3 67.6 36.76 NS 79.64 a 87.41 a 131 b 41.3 0.02 13‐HODE 302 309.67 119.44 NS 364.14 301.73 252.77 98.5 NS 13‐oxoODE 31.97 19.18 2.09 NS 36.47 10.58 23.45 15.66 NS 5‐HETE 13.38 20.59 11.04 NS 12.62 29.75 5.55 10.58 NS 11‐HETE 8.65 7.98 4.69 NS 7.48 9.02 8.43 4.09 NS 15‐HETE 10.31 8.64 5.36 NS 10.72 11.8 5.82 4.87 NS 20‐HETE 26.45 28.45 1.7 NS 5.16 32.55 6.65 16.44 NSEPA=eicosapentaenoic acid; DHA=docosahexaenoic acid; HODE=hydroxyoctadecadienoic acid; oxoODE=oxooctadecadienoic acid; HETE= hydroxyeicosatetraenoic acid. a,b,c Means in same row with different letter differ between sampling timepoint, P < 0.05. NS= non‐significant effect, P > 0.05.