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  • PF-562271 Besides being an energy storing tissue adipose tis


    Besides being an energy storing tissue, adipose tissue acts as an active endocrine organ that secretes a number of biologically active adipokines involved in multiple physiological processes such as inflammation and lipid and glucose metabolism, with direct and indirect effects on reproduction [15,16]. Adiponectin (known as AdipoQ, Acrp30, apM1, and GBP28) is an adipokine that plays an important role in the control of lipid metabolism, glucose homeostasis and insulin sensitivity, after binding to its two receptors (AdipoR1 and AdipoR2) [14,17,18]. Both adiponectin and its receptors have been identified in bovine granulosa cells, theca cells, corpora lutea, oocytes, and cumulus PF-562271 [17]. Once activated, AdipoR1 is more prominent in AMP-activated protein kinase (AMPK) phosphorylation, whereas AdipoR2 is involved in the activation of peroxisome proliferator-activated receptors (PPARs) [19]. AMPK is a metabolic sensor of the cellular energy state and plays an important role in the regulation of lipid, carbohydrate and protein metabolism of peripheral and central tissues [5,19]. Besides, in the ovary, AMPK modulates cellular proliferation and survival, as well as some reproductive functions such as ovarian steroidogenesis and oocyte maturation [14]. Therefore, adiponectin and AMPK may be important fuel sensors required for the growth of follicles, oocytes, and embryos. Based on the above, the aim of this study was to determine the expression of adiponectin and some of its downstream effectors (AdipoR1, AdipoR2, AMPK, CPT1 and ACOX1) in ovarian follicles of control cows and cows with spontaneous COD. We also aimed to evaluate some metabolic sensors such as insulin, glucose, NEFA, triacylglycerol, cholesterol, BHB and adiponectin in plasma and follicular fluid of control cows and cows with spontaneous COD.
    Materials and methods
    Discussion The increasing demand in milk production has consequences on the reproduction rates of dairy cows, with important economic losses [35,36]. Previously, we have shown alterations in insulin signaling pathways in animals with COD [28]. These pathways have important effects on reproduction functions and are regulated by several molecules including metabolites (glucose, fatty acids, etc.) and other hormones (adiponectin, ghrelin, etc.), which act through energy sensors (AMPK, PPARs, etc.) [5,14,37]. In the present study, despite the similar plasma values in most of the metabolites analyzed, in follicular fluid of COD animals we detected lower glucose and triacylglycerol concentrations along with higher NEFA, cholesterol and BHB concentrations. Glucose plays an essential role in ovarian metabolism, being its main source of energy [[38], [39], [40]]. The main source of glucose in the follicular fluid is probably blood, so the lower glucose concentration found in cystic follicles compared to the controls and the lower concentration in follicular fluid related to that in plasma in cows with COD are probably due to a greater anaerobic glycolysis [40,41]. Furthermore, since VLDL-triacylglycerol does not pass through the follicular wall [40,42], the higher levels of NEFA found in follicular fluid of cystic follicles could be a consequence of triacylglycerol hydrolysis, and its availability would favor its oxidation to obtain energy. Moreover, in cystic follicles, we detected higher protein expression of CPT1 and ACOX1, two key enzymes involved in mitochondrial and peroxisomal beta-oxidation respectively. In this sense, Elis et al. [43] have demonstrated the importance of fatty acid oxidation and synthesis in granulosa cells of cows for sustaining follicular growth. On the other hand, the increase in BHB and cholesterol concentrations in follicular fluid of cysts could be related to the higher availability of acetyl-CoA from the increased fatty acid oxidation [44]. Also, the systemic cholesterol concentration could contribute to its increase in the follicular fluid of cysts.