Fibroblast growth factor-21 improves insulin action in nonlactating ewes.

During metabolically demanding physiological states, ruminants and other mammals coordinate nutrient use among tissues by varying the set point of insulin action. This set point is regulated in part by metabolic hormones with some antagonizing (e.g., growth hormone and TNFα) and others potentiating (e.g., adiponectin) insulin action. Fibroblast growth factor-21 (FGF21) was recently identified as a sensitizing hormone in rodent and primate models of defective insulin action. FGF21 administration, however, failed to improve insulin action in dairy cows during the naturally occurring insulin resistance of lactation, raising the possibility that ruminants as a class of animals or lactation as a physiological state are unresponsive to FGF21. To start addressing this question, we asked whether FGF21 could improve insulin action in nonlactating ewes. Gene expression studies showed that the ovine FGF21 system resembles that of other species, with liver as the major site of FGF21 expression and adipose tissue as a target tissue based on high expression of the FGF21 receptor complex and activation of p44/42 extracellular signal-regulated kinase (ERK1/2) following exogenous FGF21 administration. FGF21 treatment for 13 days reduced plasma glucose and insulin over the entire treatment period and improved glucose disposal during a glucose tolerance test. FGF21 increased plasma adiponectin by day 3 of treatment but had no effect on the plasma concentrations of total, C16:0-, or C18:0-ceramide. Overall, these data confirm that the insulin-sensitizing effects of FGF21 are conserved in ruminants and raise the possibility that lactation is an FGF21-resistant state.

Temporal kinetics of bovine mammary IgG secretion into colostrum and transition milk.

Neonatal calf survival and health is predominantly dependent on sufficient consumption of immunoglobulin G (IgG) and the resulting transfer of passive immunity (TPI). In this study, we investigate the potential for continued IgG secretion and temporal kinetics of mammary IgG output in sequential milkings performed at 0, 4, 16, 28, 40, and 52 hr postcalving in Holstein dairy cows. For colostrum (0 hr), we also scrutinize the relationships between IgG concentration, volume, refractometer readings (˚Bx values, Brix) and concentration of sugars (lactose and glucose). Mammary transcripts postpartum (0 hr) indicated that active IgG secretion continues beyond the first milking (colostrum; n = 4 to 5). IgG measurements at the different timepoints indicated that colostrum represents only 25.1% of the total IgG produced across the 6 sequential milking timepoints, with a substantial 48.9% being secreted into transition milk over the next 3 timepoints (4-, 6-, and 28-hr) combined. The differences on the basis of IgG concentrations across 0-, 4-, and 16-hr milking timepoints were not statistically significant (P = 0.1522; n = 9). For colostrum, volume remained highly variable, even with induced let-down prior to milking (n = 27). Nonetheless, colostrum IgG secretion was significantly co-regulated with volume (R2 = 0.915; P < 0.001; n = 18), an association that was stronger than that measured for lactose (R2 = 0.803; P < 0.001; n = 18) and glucose (R2 = 0.467; P = 0.002; n = 17). Comparing colostrum ˚Bx values to absolute IgG concentrations showed no correlation (R2 = 0.127; P = 0.07; n = 27); biochemical separation of colostrum components indicated that both proteins and nonprotein solutes could affect ˚Bx values (P < 0.0001 for both; n = 5). This suggests that ˚Bx values do not reasonably indicate IgG concentration to serve as a measure of "colostrum quality." Additionally, our finding that early transition milk (4-, 6-, and 28-hr) can contribute substantially more IgG than colostrum forces a rethink of existing feeding paradigms and means to maximize TPI in calves. Collectively, our results reveal the remarkable value of early transition milk and caveats to colostrum assessments that could advance application in enhancing neonatal calf health.