17beta-estradiol upregulates the expression of peroxisome proliferator-activated receptor alpha and lipid oxidative genes in skeletal muscle

Abstract

This study examined the actions of 17β-estradiol (E 2 ) and progesterone on the regulation of the peroxisome proliferator-activated receptors (PPARα and PPARγ) family of nuclear transcription factors and the mRNA abundance of key enzymes involved in fat oxidation, in skeletal muscle. Specifically, carnitine palmitoyltransferase I (CPT I), β-3-hydroxyacyl CoA dehydrogenase (β-HAD), and pyruvate dehydrogenase kinase 4 (PDK4) were examined. Sprague-Dawley rats were ovariectomized and treated with placebo (Ovx), E 2 , progesterone, or both hormones in combination (E+P). Additionally, sham-operated rats were treated with placebo (Sham) to serve as controls. Hormone (or vehicle only) delivery was via time release pellets inserted at the time of surgery, 15 days prior to analysis. E 2 treatment increased PPARα mRNA expression and protein content (P<0·05), compared with Ovx treatment. E 2 also resulted in upregulated mRNA of CPT I and PDK4 (P<0·05). PPARγ mRNA expression was also increased (P<0·05) by E 2 treatment, although protein content remained unaltered. These data demonstrate the novel regulation of E 2 on PPARα and genes encoding key proteins that are pivotal in regulating skeletal muscle lipid oxidative flux.

Testosterone or 17β-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes

“…It has been shown previously that PDK4 activity is enhanced at high rates of fatty acid oxidation, which causes a consequent inhibitory effect on glucose oxidation (for review, Sugden & Holness (2006)). Consistent to our mRNA expression data, E 2 treatment increased PDK4 gene expression in ovariectomized female rats, (Campbell et al 2003), suggesting a regulative role of E 2 in skeletal muscle lipid metabolism. In contrast to this, our data showed that E 2 treatment-mediated fatty acid oxidation was only observed in myotubes from male donors and not in the female donors.…”

Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat

“…It is possible that estrogen may be playing a protective role in terms of minimizing the impact of restriction on skeletal muscle mitochondrial biogenesis. Estrogen treatment of female ovariectomized rats increases the mRNA and enzyme activity of lipid oxidative enzymes (5,6) in skeletal muscle and mitochondrial biogenesis in blood vessels (32), and PGC-1␣ is a known activator of the estrogen receptor (33). However, our finding of lower mtTFA mRNA and a tendency for lower PGC-1␣ mRNA following reductions in litter size suggests that skeletal muscle mitochondria from adult females is vulnerable to particular insults, at least in early postnatal life, although the mechanisms for this remain unclear.…”

PPAR-α Contributes to the Anti-Inflammatory Activity of 17β-Estradiol

“…Peroxisome proliferator-activated receptor-␣ (PPAR-␣) is an intracellular transcription factor, activated by fatty acids, that plays a role in inflammation. Moreover, it has been previously shown that PPAR-␣ cross-talks with estrogen signaling (Campbell et al, 2003). In addition, it has been reported that PPAR-␣ activation can result in inhibition of NF-B activation and the consequent expression of inflammatory genes (De Bosscher et al, 2006).…”