Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote atherosclerosis in mice despite increasing blood concentrations of HDL cholesterol. This suggests that under these conditions, the HDL apolipoproteins (apo) produced are abnormal. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid (control), cis-9, trans-11-CLA or trans-10, cis-12-CLA (1.0% wt/wt) for 12 wk, and the effects on HDL metabolism and apoC-III levels recorded. Compared with the control and cis-9, trans-11-CLA mice, those fed the trans-10, cis-12-CLA diet had significantly higher HDL cholesterol concentrations, and had a higher incidence of hypertriglyceridemia and hepatic steatosis. Plasma apoA-I and paraoxonase concentrations were significantly lower in the trans-10, cis-12-CLA group than in the cis-9, trans-11-CLA group. These reductions were associated with decreased hepatic expression of these proteins and a shift toward lipid-poor apolipoprotein particles. The plasma apoA-II concentration increased with its corresponding mRNA concentration in the liver, and was preferentially bound to HDL in the trans-10, cis-12-CLA mice, thus explaining the increased HDL cholesterol concentrations in this group. Significant, positive associations were found between apoA-II and C-III (r=0.883, P<0.001) and between apoA-II and atherosclerosis (r=0.68, P<0.001). These results indicate that trans-10, cis-12-CLA intake modifies HDL to form a proatherogenic apoA-II containing particle and promotes phenotypic changes compatible with metabolic syndrome. Cis-9, trans-11-CLA does not promote this detrimental effect.
In human reproduction, hyperhomocysteinemia has been reported as a risk factor for early pregnancy loss and congenital birth defects. Hyperhomocysteinemia is also recognized as a cause of maternal obstetric complications such as preeclampsia. The role of plasma hyperhomocysteinemia in female fertility was examined using cystathionine beta synthase knockout (cbs KO) mice. Cbs KO females were infertile, showed alterations in the estrus cycle and an increased progesterone response during pseudo-pregnancy induction. Both cbs KO ovaries and ovulated oocytes showed no major morphological alterations. However, placental and uterine masses were decreased at day 18 of pregnancy and showed morphological abnormalities. In cbs-KO pregnant females, the number of uterine implantation sites was not decreased despite the low number of surviving embryos. Fertility was restored when cbs-deficient ovaries were transplanted to normal ovarectomized recipients. We detected an increased uterine expression of Grp78, a marker of endoplasmic reticulum stress, which was accompanied by the decreased levels of uterine cbs mRNA in both hyperhomocysteinemic heterozygous (fertile) and homozygous (non-fertile) females. Our results indicate that cbs -/- female infertility is a consequence of the uterine failure and demonstrate that uterine endoplasmic reticulum stress and cbs expression are not determinant of infertility, suggesting that uterine dysfunction is a consequence of either hyperhomocysteinemia or other factor(s) in the uterine environment of cbs -/- animals. In summary, these studies demonstrate the potential importance of homocysteine levels for uterine handling of embryos.
Cannabis
sativa L. produces over
200 known secondary metabolites that contribute to its distinctive
aroma. Studies on compounds traditionally associated with the scent
of this plant have focused on those within the terpenoid class. These
isoprene-derived compounds are ubiquitous in nature and are the major
source of many plant odors. Nonetheless, there is little evidence
that they provide the characteristic “skunk-like” aroma
of cannabis. To uncover the chemical origins of this
scent, we measured the aromatic properties of cannabis flowers and concentrated extracts using comprehensive two-dimensional
gas chromatography equipped with time-of-flight mass spectrometry,
flame ionization detection, and sulfur chemiluminescence. We discovered
a new family of volatile sulfur compounds (VSCs) containing the prenyl
(3-methylbut-2-en-1-yl) functional group that is responsible for this
scent. In particular, the compound 3-methyl-2-butene-1-thiol was identified
as the primary odorant. We then conducted an indoor greenhouse experiment
to monitor the evolution of these compounds during the plant’s
lifecycle and throughout the curing process. We found that the concentrations
of these compounds increase substantially during the last weeks of
the flowering stage, reach a maximum during curing, and then drop
after just one week of storage. These results shed light on the chemical
origins of the characteristic aroma of cannabis and
how volatile sulfur compound production evolves during plant growth.
Furthermore, the chemical similarity between this new family of VSCs
and those found in garlic (allium sativum) suggests an opportunity to also investigate their potential health
benefits.
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