The list of signals orchestrating metabolic adaptations in dairy cows during the transition from late pregnancy (LP) to early lactation (EL) is incomplete. This dissertation investigated the role of three categories of signals known to drive adaptations in other conditions and species. In Chapter 3, I explored the possibility that the acute phase protein orosomucoid 1 (ORM1) contributes to insufficient appetite during the transition from LP to EL by activating the leptin receptor as it does in rodents. ORM1 increased from LP to EL but was not elevated in other physiological conditions associated with depressed appetite. In addition, ORM1 did not activate signal transducer and activator of transcription 3 via the leptin receptor in vitro. These data do not support ORM1 as a signal regulating appetite via the leptin receptor in cattle. In rodents, increased inflammatory tone in liver and adipose tissue has been implicated in insulin resistance. Dairy cows experience insulin resistance in EL and have elevated circulating biomarkers of inflammation, but little is known about tissue-localized inflammation. In Chapter 4, I asked whether inflammatory tone is increased in liver and adipose tissue during the transition from LP to EL. I measured gene expression of inflammatory genes in these tissues, but changes were unremarkable. Similar results were obtained when measuring inflammatory gene expression in stromal vascular cells (SVC), the cell compartment of adipose tissue enriched with immune cells. These data do not support a rise in local inflammation in liver and adipose tissue of cows experiencing a healthy transition period. miRNAs regulate level and translation of target mRNA and regulate adipose tissue metabolism in rodents. In Chapter 5, I investigated this mode of regulation by sequencing miRNA in LP and EL adipose tissue in dairy cows. Six miRNAs out of 415 total had expression > 500 rpm and differed > 2-fold between LP and EL. Among those, miR-378 was predominantly expressed in adipocytes and regulated by energy balance and plasma insulin. Altough bioinformatics analysis yielded 675 potential mRNA targets, only 57 appears to relate to metabolic changes occuring during the transition period. Functional studies are needed to ascertain the role of miR-378 in adipocytes during the transition from LP to EL.