The metabolism of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol, and lariciresinol by human fecal microflora was investigated to study their properties as mammalian lignan precursors. The quantitative analyses of lignan precursors and the mammalian lignans enterolactone and enterodiol were performed by HPLC with coulometric electrode array detector. The metabolic products, including mammalian lignans, were characterized as trimethylsilyl derivatives by gas chromatography-mass spectrometry. Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol were converted to mammalian lignans only. Several metabolites were isolated and tentatively identified as for syringaresinol and arctigenin in addition to the mammalian lignans. Metabolites of 7-hydroxymatairesinol were characterized as enterolactone and 7-hydroxyenterolactone by comparison with authentic reference compounds. A metabolic scheme describing the conversion of the most abundant new mammalian lignan precursors, pinoresinol and lariciresinol, is presented.
Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, 22.8-36.2 years of age, who were discordant (ΔBMI >3 kg/m(2), mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (ΔBMI <3 kg/m(2), n = 14) for body weight, and assessed their detailed mitochondrial metabolic characteristics: mitochondrial-related transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount, mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS) protein levels. We report global expressional downregulation of mitochondrial oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA-dependent translation system, and protein levels of the OXPHOS machinery in the obese compared with the lean co-twins. Pathway analysis indicated downshifting of fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic acid cycle, which inversely correlated with adiposity, insulin resistance, and inflammatory cytokines. Our results suggest that mitochondrial biogenesis, oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in acquired obesity, and are associated with metabolic disturbances already at the preclinical stage.
Our data highlight a strong relationship of reduced NAD(+)/SIRT pathway expression with acquired obesity, inflammation, insulin resistance, and impaired mitochondrial protein homeostasis in SAT.
Sesamin, a major sesame seed lignan, has many biological actions. The specific mechanisms for most of these actions as well as the full metabolic pathway of sesamin in humans are unclear. Two experiments were carried out to determine whether postprandial plasma enterolactone is related to sesamin concentration in sesame seeds and whether enterolactone is the major product of the in vitro fermentation of sesamin. Four subjects (3 women, 1 man) were given a single dose of sesame seeds after they consumed a low-lignan diet for 1 wk. Blood was collected at baseline and at time intervals after intake and plasma was analyzed for plant and mammalian lignan concentrations. Additionally, pure sesamin standard was incubated in vitro with human fecal inoculum to mimic the fermentation process in human gut. We calculated individual pharmacokinetic variables and found high interindividual variation in the plasma plant lignan concentrations. The mammalian lignan appearance rate in plasma shows that sesamin is a major precursor of enterolactone in vivo. In the in vitro experiment, enterolactone was the major metabolite and 3 intermediates were identified, allowing the elucidation of sesamin metabolism in humans. Enterolactone was the major metabolite of sesamin both in vivo and in vitro. The abundance of sesamin in sesame seeds indicates that they are a major food source of enterolactone precursors.
Manufacturing of healthy whole-grain foods demands knowledge of process-induced changes in macro-, micro- and non-nutrients. The high content of dietary fibre is a challenge in relation to good product texture and sensory quality. The stability and bioavailability of bioactive compounds have a marked influence on the health effects of cereal foods. It was confirmed that sterols, folates, tocopherols and tocotrienols, alkylresorcinols, lignans, phenolic acids and total phenolics are concentrated in the bran layers of the rye grain, and are only present at low levels in the flour endosperm. The levels of folate and easily-extractable phenolic compounds increase in germination and sourdough baking, but there are negligible changes in the levels of sterols, lignans and alk(en)ylresorcinols. The levels of tocopherols and tocotrienols are reduced during the sourdough fermentation. In conclusion, many of the bioactive compounds in whole-grain rye are stable during food processing, and their levels can even be increased with suitable processing.
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