The health of dairy cows is endangered by metabolic changes around calving (Ospina et al. 2010; Celi and Gabai 2015). The present study showed that PIO supplementation improved the metabolic parameters and insulin sensitivity index of dairy cows during the transition period.
Plasma NEFA concentration is a well-known biomarker of lipolysis (Tordjman et al. 2003). Previous studies have indicated that TZD administration reduced the plasma NEFA concentration during the postpartum period (Smith et al. 2007; Smith et al. 2009; Schoenberg and Overton 2011). Ghoreishi (2012) also showed that supplementation of 4 mg PIO/kg BW was able to reduce the concentration of NEFA. It has been suggested that TZD supplements decrease insulin resistance by reducing plasma NEFA in dairy steers (Kushibiki et al. 2001). The effect of PIO supplementation on lowering plasma NEFA concentration is explained by two potential mechanisms including: 1) increasing dry matter intake during the postpartum period (Smith et al. 2007; Smith et al. 2009; Ghoreishi 2012) which mitigated NEB, and 2) re-esterification of fatty acids, reducing mobilization, and stimulating liver capacity for free fatty acids oxidation (Tordjman et al. 2003; Yousefi et al. 2016).
In addition to NEFA, BHBA is another metabolite that is associated with energy balance and liver functioning in lactating cows (Ospina et al. 2010). In this study, the decrease in BHBA concentration with PIO intake was consistent with the study of Yousefi et al. (2016), who showed that feeding 6 mg PIO per kg BW decreased plasma BHBA concentration in dairy cows. Smith et al. (2007) also stated that administration of 2 or 4 mg TZD per kg decreased plasma BHBA concentration. Nevertheless, others did not find plasma BHBA changes (Ghoreishi 2012; Gheise et al. 2018) or even observed higher plasma BHBA (Smith et al. 2009) after administration of TZDs in dairy cows. Decreased plasma NEFA availability and increased hepatic capacity for free fatty acids oxidation are the main reasons considered to explain the reduced BHBA in PIO-supplemented cows (Ide et al. 2000; Allen et al. 2005; Yousefi et al. 2016).
In the present study, PIO supplementation had no significant effect on plasma insulin concentration throughout the study; however, it caused higher plasma concentrations during calving and the first week after calving in PIO-treated cows. In agreement with our results, Schoenberg and Overton (2011) reported that TZD did not significantly alter plasma insulin concentrations. Although we did not measure the DMI, increasing dry matter intake has been reported to increase plasma glucose (Wolden-Hanson et al. 2002; Larsen et al. 2003; Smith et al. 2007; Ghoreishi 2012) which in turn can increase the insulin concentration. The results of current study showed that PIO supplementation did not influenced mean plasma glucose concentrations, which was in agreement with the results of Smith et al. (2007) and Ghoreishi (2012); however, the interaction effect of treatment and time on plasma glucose revealed that it was increased at calving in PIO-treated cows. Consistently, some studies have suggested that administration of 2 or 4 mg TZD /BW increased the concentration of glucose during the periparturient period as a result of the increased liver glycogen to triglyceride ratio and hepatic gluconeogenesis (Smith et al. 2009; Schoenberg and Overton 2011).
The PIO supplementation increased the plasma IGF-1 concentration and the IGF-I to GH ratio, but did not affect the GH concentration. Consistent results was reported by Yousefi et al. (2016), but, Gheise et al. (2018) stated that PIO supplementation did not affect IGF-I plasma concentrations, likely due to the use of PIO in short term feeding period (28 days). The high-producing dairy cows experience low plasma IGF-1 and high GH concentrations during the transition period (Lucy 2004). The uncoupling of the somatotropic axis in postpartum cows is probably due to a decrease in hepatic growth hormone receptor 1A (GHR 1A) during the prepartum period (Lucy 2004). Therefore, increasing the GHR 1A receptor and improving dry matter intake, and reducing the NEB may cause subsequent recoupling of this axis (Butler et al. 2003). In the present study, NEB indices, such as NEFA and BHBA, were significantly decreased. These effects were also supported by the previous findings showing higher dry matter intake and lower NEB during the postpartum in TZD-treated cows (Smith et al. 2007; Smith et al. 2009). It could be postulated that the higher IGF-I concentration per insulin unit in the PIO-supplemented cows is due to the possible improvement in the response of the liver and other peripheral tissues to insulin. Probably, the effect of PIO on increasing liver's sensitivity to insulin and more expression of the GHR 1A receptor resulted in more efficient IGF-1 production in the liver.
The results also showed that PIO supplementation had no effect on milk production, but it did increase the percentage of milk fat. In line with this result, Yousefi et al. (2016) showed that PIO supplementation reduced the milk fat percentage in dairy cows. It has been also shown that administration of 4 mg TZD per kg BW before calving tended to reduce milk fat percentage in dairy cows (Smith et al. 2009). As a component influencing blood fat metabolites and body fat mobilization, it could be postulated that the reduced milk fat is a consequence of lowering blood NEFA and other fat metabolites that are directly involved in the milk fat synthesis (Lucy 2004). On the other hand, TZD administration has shown to alter lipogenic gene networks in bovine mammary epithelial cells (Kadegowda et al. 2009) and therefore could change de novo fat synthesis in mammary glands. The increased percentage of milk protein in the first week after calving by supplementing PIO is probably due to the increased concentration of colostrum and milk immunoglobulins, which occurred following improving the immune function of periparturient cows. This assumption is supported by the results of previous findings where TZD administration improved the immunity of periparturient cows (Revelo and Waldron 2010) and dairy goat (Rosa et al. 2017).
Dietary PIO supplementation reduced BCS and BW loss. Consistent with our findings, it has been reported that cows fed PIO experienced lesser BCS loss during transition period (Smith et al. 2009; Yousefi et al. 2016; Gheise et al. 2018). However, no significant effect of TZD on the reduction of BCS and BW losses also has been reported (Smith et al. 2007; Schoenberg and Overton 2011). The discrepancy between the literature is likely depends on the TZD level, route of administration or duration of administration. Lower concentrations of lipolysis indices (NEFA and BHBA) indicate that PIO supplementation potentially improved the lipid metabolism and thus energy balance. In addition, less energy used to synthesis of milk fat and possibly more energy income (as dry matter) are other reasons for the reduction in BCS and BW loss.
Our findings indicated that PIO supplementation increased insulin sensitivity index. The RQUICKI-BHB index is a significant influencing factor for the relationship between baseline and dynamic glucose, NEFA, BHB, and insulin levels in ketotic cows (Djoković et al. 2017). The revised quantitative insulin sensitivity check Index (RQUICKI) and its modified variant (RQUICKI-BHB) appear to be similarly capable of estimating insulin sensitivity changes (Balogh et al. 2008). The addition of BHB to the RQUICKI index would assist in the evaluation of insulin sensitivity in a quicker and more efficient. Our findings showed that the insulin index increased in PIO- fed cows, which could be due to a decrease in NIFA and BHBA concentration. Gheise et al. (2018) and Schoenberg et al. (2011) showed that PIO and TZD treatments did not affect RQUICKI index. The RQUICKI has a poor distinguishing capacity when it applies to diagnosing reduced insulin sensitivity in cows, particularly when they are affected by metabolic diseases (Kerestes et al. 2009). Therefore, it can be assumed that the significant effect of PIO supplementation on insulin resistance in our study is due to the use of RQUICKI-BHBA values. In addition, PIO supplementation increased the plasma IGF-1 concentration and the IGF-I to GH ratio, but did not affect the GH concentration. Consistent results were reported by Yousefi et al. (2016), but Gheise et al. (2018) stated that PIO supplementation did not influence IGF-I plasma concentrations, likely due to the use of PIO in the short term feeding period (28 days). The high-producing dairy cows experience low plasma IGF-1 and high GH concentrations during the transition period (Lucy 2004). The uncoupling of the somatotropic axis in postpartum cows is probably due to a decrease in hepatic GHR 1A during the prepartum period (Lucy 2004). Therefore, increasing the GHR 1A receptor as a results of lower NEB may involve in recoupling of this axis (Butler et al. 2003).