Acetyl CoA carboxylase inactivation and meiotic maturation in mouse oocytes

Abstract

In mouse oocytes, meiotic induction by pharmacological activation of PRKA (adenosine monophosphate-activated protein kinase; formerly known as AMPK) or by hormones depends on stimulation of fatty acid oxidation (FAO). PRKA stimulates FAO by phosphorylating and inactivating acetyl CoA carboxylase (ACAC; formerly ACC), leading to decreased malonyl CoA levels and augmenting fatty-acid transport into mitochondria. We investigated a role for ACAC inactivation in meiotic resumption by testing the effect of two ACAC inhibitors, CP-640186 and Soraphen A, on mouse oocytes maintained in meiotic arrest in vitro. These inhibitors significantly stimulated the resumption of meiosis in arrested cumulus cell-enclosed oocytes, denuded oocytes, and follicle-enclosed oocytes. This stimulation was accompanied by an increase in FAO. Etomoxir, a malonyl CoA analogue, prevented meiotic resumption as well as the increase in FAO induced by ACAC inhibition. Citrate, an ACAC activator, and CBM-301106, an inhibitor of malonyl CoA decarboxylase, which converts malonyl CoA to acetyl CoA, suppressed both meiotic induction and FAO induced by follicle-stimulating hormone, presumably by maintaining elevated malonyl CoA levels. Mouse oocyte-cumulus cell complexes contain both isoforms of ACAC (ACACA and ACACB); when wild-type and Acacb(-/-) oocytes characteristics were compared, we found that these single-knockout oocytes showed a significantly higher FAO level and a reduced ability to maintain meiotic arrest, resulting in higher rates of germinal vesicle breakdown. Collectively, these data support the model that ACAC inactivation contributes to the maturation-promoting activity of PRKA through stimulation of FAO.

Melatonin regulates lipid metabolism in porcine oocytes

“…Melatonin treatment greatly increased the expression of ACACA, FASN, PPARγ, and SREBF1, illustrating the importance of LDs accumulation in oocytes . The ACACA gene plays a vital role in lipid metabolism . Uzbekova et al.…”

The consequences of porcine IVM medium supplementation with follicular fluid become reflected in embryo quality, yield and gene expression patterns

“…Two genes ( ACACA , the acetyl-CoA carboxylase and FASN , the fatty acid synthase) are involved in FA synthesis. The starting substrate for ACACA is acetyl-CoA which is transformed into malonyl CoA subsequently committing to the first step of FA synthesis 52 . The formation of new lipid droplets which stores lipids mostly in the form of triacyloglicerols is controlled by ADRP (also known as PLIN2 ).…”

Vitamin D3 regulates steroidogenesis in granulosa cells through AMP‐activated protein kinase (AMPK) activation in a mouse model of polycystic ovary syndrome

“…ACACA is an important substrate for AMPK, the phosphorylation of this molecule could exhibit the AMPK activation. 51 Growing evidence suggests that reproductive events are sensitive to metabolic cues, and the activation of the gonadal axis and fertility preservation are critically reliant on the metabolic state and the maintenance of energy reserves of the body. 52,53 As described in previous studies, AMPK is expressed in female gonad and has a key role in the ovarian function in connecting the reproductive axis with energy balance.…”

“…Because ACACA is an important substrate for AMPK, the phosphorylation of this molecule could exhibit the AMPK activation 51. The GCs were pre-incubated in the serum-free medium in the presence or absence of compound C and then stimulated or not with Aicar in serumfree medium.…”