Fetuin-A: A novel biomarker for lipolysis-induced metabolic stress in transition dairy cows

Abstract Text:

Periparturient cows that experience severe adipose tissue lipolysis are at a higher risk for inflammatory and metabolic diseases. Fetuin-A (FetA) is a glycoprotein that inhibits insulin signaling and enhances inflammatory responses in adipose tissues, which are known to exacerbate lipolytic responses in humans and rodents. However, little is known about its role during lipolysis and its use as a biomarker for metabolic stress and lactation performance in dairy cows. Our objective was to determine the dynamics of serum and adipose FetA concentrations and its association with metabolic markers during negative energy balance (NEB)-induced lipolysis at different stages of lactation. In Experiment 1, twenty-six multiparous cows were followed through the transition period. Blood samples and subcutaneous adipose tissue were collected at dry-off (DO; -51±3d), close-up (CU; -14±2d), and early lactation (EL; 7±0.5d). In Experiment 2, FetA response to lipolysis was evaluated independently of parturition-associated metabolic challenges using mid-lactation cows (DIM 119-210) assigned to one of two feeding protocols: ad libitum (AL; n=3, +EB=3.2±0.66 Mcal/d) or feed-restricted (FR; n=3, EB=-13.3 ± 0.5 Mcal/d). Blood and subcutaneous adipose tissue were collected after a 4-d period of feed restriction. FetA was determined by ELISA and western blot. Data were analyzed using a repeated measures mixed model. Serum and adipose FetA concentrations were affected by lactation stage. In Experiment 1, serum FetA concentrations were lower at EL (DO:1.31±0.06; CU:1.27±0.09; EL:1.14±0.06 mg/mL; P<0.05) when NEFA concentration was greatest (DO:0.34±0.02; CU:0.63±0.2; EL:1.19±0.14 mEq/L; P<0.05). Unlike in serum, adipose FetA expression decreased at CU (relative band density; DO:1.5±0.4; CU:0.2±0.02; EL:1.6±0.6; P<0.05). Circulating FetA concentration was higher in over-conditioned dry cows (BCS≥3.75; P<0.05) and was positively associated with BCS (R²=0.24; P<0.0001) and BCS loss (R²=0.43; P=0.0005) during the transition period. Cows with high BCS and increased serum FetA concentrations at DO had lower serum glucose concentrations at EL (P<0.05). In Experiment 2, despite the feed restriction-induced lipolysis (NEFA; FR=0.47±0.05; AL=0.09±0.08 mEq/L), neither serum nor adipose FetA concentrations were affected in mid-lactation cows (P>0.05). These results demonstrate that serum and adipose FetA concentrations during lipolytic states are determined by lactation stage and BCS around parturition. FetA is a potential novel biomarker for metabolic stress induced by lipolysis during the transition period. Future work will determine the mechanisms by which FetA affects lipolytic and inflammatory responses in adipose tissues of transition dairy cows. 

Keywords: adipose, biomarker, lipolysis