Statins downregulate ATP-binding-cassette transporter A1 gene expression in macrophages

The ATP-binding-cassette transporter A1 (ABCA1) plays an essential role in cellular cholesterol efflux and helps prevent macrophages from becoming foam cells. The statins are widely used as cholesterol-lowering agents and have other anti-atherogenic actions. We tested the effects of four different statins (fluvastatin, atorvastatin, simvastatin, and lovastatin) on ABCA1 expression in macrophages in vitro. The statins suppressed ABCA1 mRNA expression in RAW246.7 and THP-1 macrophage cell lines and in mouse peritoneal macrophages. The effect was time- and dose-dependent and was abolished by the addition of the post-reductase product, mevalonate. These findings imply that there is a possible modulation of the well-known beneficial effects of the statins on the reverse cholesterol transport pathway.     

p53 involvement in the pathogenesis of fatty liver disease

Obesity is a major health problem in industrialized societies, and fatty liver disease (hepatic steatosis) is common in obese individuals. Oxidative stress originating from increased intracellular levels of fatty acids has been implicated as a cause of hepatocellular injury in steatosis, although the precise mechanisms remain to be elucidated. p53, widely known as a tumor suppressor, has been shown often to be activated in stressed cells, inducing cell cycle arrest or death. Here we demonstrate that p53 is involved in the molecular mechanisms of hepatocellular injury associated with steatosis. We found that p53 in the nucleus is induced in the liver from two mouse models of fatty liver disease, ob/ob and a transgenic mouse model that overexpresses an active form of sterol regulatory element-binding protein-1 in the liver (TgSREBP-1), the one with obesity and the other without obesity. This activation of the p53 pathway leads to the elevation of p21 mRNA expression, which can be considered an indicator of p53 activity, because ob/ob mice lacking p53 generated by targeting gene disruption exhibited the complete restoration of the p21 elevation to wild type levels. Consistent with these results, the amelioration of hepatic steatosis caused by Srebp-1 gene disruption in ob/ob mice lowered the p21 expression in a triglyceride content-dependent manner. Moreover, p53 deficiency in ob/ob mice resulted in a marked improvement of plasma alanine aminotransferase levels, demonstrating that p53 is involved in the mechanisms of hepatocellular injury. In conclusion, we revealed that p53 plays an important role in the pathogenesis of fatty liver disease.     

The anorectic effect of neurotensin is mediated via a histamine H1 receptor in mice

Neurotensin (NT), a tridecapeptide found in the mammalian brain and peripheral tissues, induces a decrease in food intake after central administration. In this investigation, we examine whether the histaminergic system is involved in NT-induced suppression of feeding. Intracerebroventricular injection of NT (0.1–1 nmol/mouse) led to dose-dependent inhibition of food intake in fasted ddY mice. The anorectic effect induced by NT (0.1 nmol/mouse) was ameliorated upon co-administration of pyrilamine (3 nmol/mouse), an antagonist for histomine H₁ receptor. The NT-induced anorectic effect was partially ameliorated in H₁ knockout mice. The findings suggest that the H₁ receptor in part mediates the NT-induced suppression of food intake.     

Dicer has a crucial role in the early stage of adipocyte differentiation, but not in lipid synthesis, in 3T3-L1 cells

Dicer is a rate-limiting enzyme for microRNA (miRNA) synthesis. To determine the effects of Dicer on adipogenesis, we performed stage-specific knockdown of Dicer using adenovirus encoding short-hairpin RNAi against Dicer in 3T3-L1 cells. When cells were infected with the adenovirus before induction of adipocyte differentiation, Dicer RNAi suppressed the gene expression of inducers of adipocyte differentiation such as PPARγ, C/EBPα, and FAS in 3T3-L1 cells during adipocyte differentiation. Concurrently, both adipocyte differentiation and cellular lipid accumulation were cancelled by Dicer RNAi when compared with control RNAi. Meanwhile, we addressed the roles of Dicer in lipid synthesis and accumulation in the final stages of differentiation. When the differentiated cells at day 4 after induction of differentiation were infected with adenovirus Dicer RNAi, cellular lipid accumulation was unchanged. Consistent with this, Dicer RNAi had no effects on the expression of genes related to cellular lipid accumulation, including PPARγ and FAS. Thus, Dicer controls proadipogenic genes such as C/EBPα and PPARγ in the early, but not in the late, stage of adipogenesis via regulation of miRNA synthesis.     

Environmental variation in Amazonian interfluves and its effects on local mayfly assemblages

Hydrobiologia - We assessed how the variation in environmental factors influences mayfly assemblages in conserved streams of different Amazonian interfluves. We hypothesized that environmental...     

Nitrogen stocks in a riparian area invaded by N-fixing black locust (Robinia pseudoacacia L.)

Fixation of river flow passages and riverbed degradation may facilitate the development of higher floodplains with the establishment of exotic species such as black locust (Robinia pseudoacacia L.). We quantitatively evaluated the relationship between nitrogen (N) levels in black locust trees and in sediments under different flood disturbance regimes in a riparian area of the Chikuma River. In this study, allometric equations were developed for relating leaf N content to diameter at breast height of black locust. The amount of leaf N in black locust increased with distance from the river, reaching 159 kg N ha⁻¹ at 180 m from the river. There was a small difference in N content between green and fallen leaves (0.2%), and so the leaf N was almost equivalent to N input to riparian sediments. Fine sediments accumulated on the riparian area, where the amount of sediments N increased with distance from the river, ranging from 1091 ± 767 to 4953 ± 2953 kg N ha⁻¹. The N accumulation rates also increased with distance from the river, corresponding with the amount of leaf N in black locust per unit area, but the former exceeded the latter. The sediment N accumulation might be accelerated by sediment trapping effect due to riparian vegetation itself. A large input of N provided by invaded black locust might alter nutrient dynamics and native plant community structure in the riparian area.