Tissue-specific sex differences in docosahexaenoic acid and Δ6-desaturase in rats fed a standard chow diet

Abstract

Docosahexaenoic acid (DHA, 22:6n-3) is higher in the blood and tissues of females relative to males, but the underlying mechanism is not clear. The present study examined the expression of enzymes involved in the biosynthesis of DHA from short-chain n-3 polyunsaturated fatty acids in male and female rats (n = 6 for each sex). Rats were maintained on an AIN-93G diet and sacrificed at 14 weeks of age after an overnight fast. Plasma, erythrocytes, liver, heart, and brain were collected for fatty acid composition analysis and the determination of enzyme and transcription factor expression by RT-PCR and immunoblotting. Females had higher DHA concentrations in the total lipids of liver, plasma, erythrocyte, and heart (53%, 75%, 36%, and 25% higher, respectively, compared with males) with no sex differences in brain DHA concentrations. The mRNA content of Δ5-desaturase, Δ6-desaturase, and elongase 2 was 1.0-, 1.4-, and 1.1-fold higher, respectively, in the livers of female rats compared with males, with no differences in the hearts or brains. The protein content of Δ6-desaturase was also higher in females. Higher hepatic mRNA of sterol-regulatory element-binding protein 1-c and estrogen receptor α in the females suggests that lipogenic and estrogen signaling mechanisms are involved. The sex difference in DHA concentration is tissue specific and is associated with higher Δ6-desaturase expression in females relative to males, which appears to be limited to the liver.

Hepatic and plasma sex differences in saturated and monounsaturated fatty acids are associated with differences in expression of elongase 6, but not stearoyl-CoA desaturase in Sprague–Dawley rats

“…The concentration of 18:0 was also higher in the hepatic triacylglycerols of females as compared with males, which was the only sex difference in triacylglycerol fatty acid composition (data not shown). Total hepatic fatty acid concentrations did not differ between the sexes, although there were significant differences between n-3 and n-6 PUFA examined previously (Kitson et al 2012). Sex differences were not observed in MUFA composition of brain, heart or adipose tissue (data not shown).…”

Alterations in levels and ratios of n–3 and n–6 polyunsaturated fatty acids in the temporal cortex and liver of vervet monkeys from birth to early adulthood

“…It is during this period of time that PUFAs such as DHA and ARA accumulate in the central nervous system [44]. This “DHA accretion spurt” has been associated with a marked increase in Δ-6 desaturase (enzymatic product of FADS1 ) activity in late embryonic and postnatal rodent brain [30, 32, 45]. However, less is known about the accretion of these FAs in the brain during adolescence and throughout adulthood.…”

“…Once formed, LC-PUFAs are released into circulation as complex lipids (phospholipids, lyso-phospholipids, triglycerides, and cholesterol esters) or free fatty acids. These LC-PUFAs can then be specifically transported into tissues such as the brain [30–36]. Additionally, cells within the brain, including astrocytes and some neurons, have been shown to synthesize low levels of ARA and DHA from LA and ALA, respectively, in vitro [37].…”

Dietary docosahexaenoic acid supplementation reduces SERCA Ca2+ transport efficiency in rat skeletal muscle

“…The diet was purged under nitrogen gas and stored at À75 C in between feeding sessions. The fatty acid composition of the diets was confirmed upon arrival by gas chromatography as described in detail elsewhere (Kitson et al, 2012) and monitored throughout the feeding protocol to confirm fatty acid stability (data not shown). The dietary protocol lasted for 8 weeks beginning at 20 weeks of age.…”