Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis

We performed silencing and overexpression studies of flavin containing monooxygenase (FMO) 3 in hyperlipidemic mouse models to examine its effects on trimethylamine N-oxide (TMAO) levels and atherosclerosis. Knockdown of hepatic FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also observed significant decreases in hepatic lipids and in levels of plasma lipids, ketone bodies, glucose, and insulin. FMO3 overexpression in transgenic mice, on the other hand, increased hepatic and plasma lipids. Global gene expression analyses suggested that these effects of FMO3 on lipogenesis and gluconeogenesis may be mediated through the PPARα and Kruppel-like factor 15 pathways. In vivo and in vitro results were consistent with the concept that the effects were mediated directly by FMO3 rather than trimethylamine/TMAO; in particular, overexpression of FMO3 in the human hepatoma cell line, Hep3B, resulted in significantly increased glucose secretion and lipogenesis. Our results indicate a major role for FMO3 in modulating glucose and lipid homeostasis in vivo, and they suggest that pharmacologic inhibition of FMO3 to reduce TMAO levels would be confounded by metabolic interactions.     

Correlations between net auxin and secondary xylem development in young Populus deltoides

Stems of cottonwood ( Populs deltoides Bartr. ex Marsh.) plants grown under different conditions were examined to determine the relation between net endogenous auxin yields and the acropetal advance of the primary-secondary vascular transition zone (TZ). In all treatments, the internode yielding maximum net auxin activity, as determined by the Avena curvature bioassay, closely corresponded with the internode in which the TZ occurred. Under short-day (SD) dormancy-inducing conditions, auxin yield declined steadily while the maximum auxin peak and the TZ shifted toward younger internodes. Auxin yields from these plants were extremely low after 5 weeks of SD compared with those from long-day (LD) plants. The only consistent auxin yield was obtained from internodes subtending young leaves beneath the apical bud. Plants placed in SD for 3 weeks and then returned to LD conditions showed an immediate increase in auxin yield in the stem, and the progressive acropetal advance of the TZ under SD was reversed. Therefore, within 7 LD the positions of the TZ and peak auxin yield corresponded to those observed before the imposition of SD Fully dormant plants placed in LD showed a dramatic rise in auxin yields during the first 2 weeks of renewed growth. Although low levels of auxin were found in the newly developing shoots after 6 LD, yields increased rapidly after 9 and 14 LD. The position of the TZ corresponded with the peak of net auxin activity after 9 and 14 LD.