Growth Hormone Promotes Lipolysis and Impairs Insulin Sensitivity by Activating the ERK/HSL Signaling Pathway in Bovine Adipocytes

The physiological adaptation responses of peripartum cows to negative energy balance, including fat mobilization and insulin resistance, are controlled by hormones. Excessive growth hormone (GH) promotes fat mass loss and insulin resistance in nonruminants. Despite elevated circulating GH in postpartum cows, its regulatory mechanisms on lipid metabolism and insulin signaling pathways in bovine adipocytes remain unresolved. This research study intends to examine the effects that GH has on lipolysis and insulin sensitivity within bovine adipocytes and provide mechanistic insights. We discovered that GH stimulates lipolysis and compromised insulin sensitivity, as evidenced by elevated glycerol release, reduced triglyceride accumulation, and diminished lipid droplet formation, along with impaired insulin-mediated phosphorylation of protein kinase B (AKT) in GH-treated adipocytes. The combination of GH and isoproterenol exacerbated the insulin insensitivity and lipolysis induced by GH. Phosphorylation levels of ERK and HSL were elevated in adipocytes treated with GH, suggesting that GH activated the ERK/HSL signaling pathway. The mRNA abundance of cell death-inducing DNA fragmentation factor-α-like effector c and perilipin 1 was downregulated by GH in adipocytes. Importantly, inhibiting ERK and HSL (hormone sensitive lipase; encoded by LIPE) attenuated GH-induced lipolysis and insulin insensitivity. Collectively, GH enhances lipolysis and impairs insulin sensitivity in bovine adipocytes via activating the ERK/HSL signaling pathway at least partially. Therefore, inhibiting the ERK/HSL signaling pathway may be a promising means to avoid excessive fat mobilization and insulin resistance in dairy cows during the peripartum period.