Insulin signaling and insulin response in subcutaneous and retroperitoneal adipose tissue in Holstein cows during the periparturient period

Abstract

Adipose tissue response to endocrine stimuli, such as insulin, is crucial for metabolic adaptation at the onset of lactation in dairy cows. However, the exact molecular mechanisms behind this response are not well understood. Thus, the aim of this study was to determine the dynamics in protein expression and phosphorylation of key components in insulin signaling in subcutaneous (SCAT) and retroperitoneal (RPAT) adipose tissues of Holstein dairy cows. Furthermore, by ex vivo examinations, response to insulin was assessed in SCAT and RPAT at different time points during the periparturient period. Biopsy samples were taken 42 d prepartum, and 1, 21, and 100 d postpartum. Insulin and glucose concentrations were measured in blood serum in consecutive serum samples from d −42 until d +100. After parturition, the majority of the key components were downregulated in both adipose tissues but recovered by d +100. The extent of hormone-sensitive lipase phosphorylation increased postpartum and remained high throughout the experimental period. Strong differences in molecular response were observed between the 2 depots. The RPAT expressed a remarkably greater extent of AMP-activated kinase phosphorylation compared with SCAT, indicating that AMP-activated kinase as an energy sensor is highly active particularly in RPAT in times of energy scarcity. Consequently, this depot expressed a greater extent of hormone-sensitive lipase phosphorylation over the whole experimental period. Insulin response after parturition appeared to be greater in RPAT too, due to the significantly greater expression of the insulin receptor at d +21 and +100. Although insulin concentrations in plasma were low postpartum, the depot-specific changes in molecular modulation of insulin signaling and insulin response suggested that both adipose tissue depots studied were contributing to the periparturient homeorhetic adaptation, although most likely to a different extent.

Methionine supplementation during a hydrogen peroxide challenge alters components of insulin signaling and antioxidant proteins in subcutaneous adipose explants from dairy cows

“…At least in nonruminants, insulin signaling controls glucose absorption, lipogenesis, lipolysis, and protein synthesis (Kenéz et al, 2019), all of which play vital roles in adipose tissue metabolism. A transient state of insulin resistance around parturition prevents peripheral tissues from using glucose, to guarantee glucose supply for the mammary gland (Contreras et al,…”

Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

“…This provides evidence that adipose tissue with more ceramides would more suppress insulin sensitivity and have an enhanced sphingolipid dynamic. In contrast to SCAT, Kenéz et al demonstrated that Akt and HSL phosphorylation were greater in the insulin signaling pathway in dairy cow RPAT during the peripartum period [11]. This indicated that RPAT may be more sensitive and responsive in insulin signaling than SCAT.…”

“…Retroperitoneal (RPAT) and subcutaneous adipose tissue (SCAT) in dairy cows are suggested to be different in insulin signaling, proinflammatory signaling, and lipolytic activity [11][12][13]. It was demonstrated that RPAT is more responsive than SCAT regarding the insulin signaling pathway, with greater protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, as well as greater fatty acid synthase (FAS) expression, shown in an ex vivo study [11]. Moreover, RPAT had greater proinflammatory cytokine and chemokine messenger RNA [8], and Maceyka and Spiegel [9].…”

Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

“…This provides evidence that adipose tissue with more ceramides would more suppress insulin sensitivity and have an enhanced sphingolipid dynamic. In contrast to SCAT, Kenéz et al demonstrated that Akt and HSL phosphorylation were greater in the insulin signaling pathway in dairy cow RPAT during the peripartum period [9]. This indicated that RPAT may be more sensitive and responsive in insulin signaling than SCAT.…”

“…However, adipose metabolism differs to some extent between adipose depots. Retroperitoneal (RPAT) and subcutaneous adipose tissue (SCAT) in dairy cows are suggested to be different in insulin signaling, proin ammatory signaling, and lipolytic activity [9][10][11]. It was demonstrated that RPAT is more responsive than SCAT regarding the insulin signaling pathway, with greater Akt and AMPK phosphorylation, as well as greater FAS expression, shown by an ex vivo study [9].…”