Regulatory effects of the saturated fatty acids 6:0 through 18:0 on hepatic low density lipoprotein receptor activity in the hamster.

The plasma concentration of cholesterol carried in low density lipoproteins is principally determined by the level of LDL receptor activity (Jm) and the LDL-cholesterol production rate (Jt) found in animals or man. This study delineates which saturated fatty acids alter Jm and Jt and so increase the plasma LDL-cholesterol level. Jm and Jt were measured in vivo in hamsters fed a constant level of added dietary cholesterol (0.12%) and triacylglycerol (10%), where the triacylglycerol contained only a single saturated fatty acid varying in chain length from 6 to 18 carbon atoms. After feeding for 30 d, the 12:0, 14:0, 16:0, and 18:0 fatty acids, but not the 6:0, 8:0, and 10:0 compounds, became significantly enriched in the liver total lipid fraction of the respective groups fed these fatty acids. However, only the 12:0, 14:0, and 16:0 fatty acids, but not the 6:0, 8:0, 10:0, and 18:0 compounds, suppressed Jm, increased Jt, and essentially doubled plasma LDL-cholesterol concentrations. Neither the 16:0 nor 18:0 compound altered rates of cholesterol synthesis in the extrahepatic organs, and both lowered the hepatic total cholesterol pool. Thus, the different effects of the 16:0 and 18:0 fatty acids could not be attributed to a difference in cholesterol delivery to the liver. Since these changes in LDL kinetics took place without an apparent alteration in external sterol balance, the regulatory effects of the 12:0, 14:0, and 16:0 fatty acids presumably are mediated through some change in a putative intrahepatic regulatory pool of sterol in the liver.     

Fatty acids regulate hepatic low density lipoprotein receptor activity through redistribution of intracellular cholesterol pools.

When the intake of dietary cholesterol in the hamster is constant, feeding the saturated 14:0 fatty acid (n-tetradecanoic acid) elevates the plasma low density lipoprotein (LDL) cholesterol concentration from 72 to 204 mg/dl, while the monounsaturated 18:1 fatty acid (cis-9-octadecenoic acid) lowers this level to 28 mg/dl. The 14:0 fatty acid lowers the hepatic cholesteryl ester concentration from 12 to 5 mg/g, while the abundance of this fatty acid in the ester fraction is increased 13-fold. Hepatic LDL receptor activity is depressed to 41% of control, while the LDL cholesterol production rate is increased to 132%. These changes account for the 3-fold increase in the plasma LDL cholesterol concentration. In contrast, feeding the 18:1 fatty acid increases hepatic cholesteryl ester concentration to 21 mg/g, and the abundance of this acid in the esters is increased 1.4-fold. Hepatic receptor activity is increased to 145%, while the production rate is suppressed to 68% of control. These changes account for the decrease in plasma LDL cholesterol level to 28 mg/dl. Despite these marked changes in LDL metabolism, however, the 14:0 and 18:1 fatty acids cause no change in net cholesterol balance across the liver. These results suggest that there are two fundamentally different mechanisms regulating hepatic LDL metabolism. One involves changes in net sterol balance across the liver brought about by alterations in the rate of cholesterol or bile acid absorption across the intestine, while the second is articulated through a redistribution of the putative sterol regulatory pool within the hepatocyte that is dictated by the type of long-chain fatty acid that reaches the liver.     

Early type I interferon-mediated signals on B cells specifically enhance antiviral humoral responses

Type I interferons (IFN-I) limit viral spread by inducing antiviral genes in infected target cells and by shaping the adaptive response through induction of additional cytokines. Vesicular stomatitis virus (VSV) efficiently triggers the production of IFN-I in mice, and it is suggested that IFN-alpha is induced after binding of VSV to TLR7 in infected cells. Our study with virus-specific B cell receptor-transgenic mice demonstrates here that IFN-I directly fuel early humoral immune responses in vivo. VSV-specific B cells that lacked IFN-alpha/beta receptors were considerably impaired in plasma cell formation and in generating antiviral IgM. At low viral titers, production of IFN-alpha following VSV infection was independent of TLR7-mediated signals. Interestingly, however, TLR7 ligation in B cells increased the formation of early antiviral IgM. These findings indicate that IFN-alpha-mediated augmentation of specific B cell responses is a partially TLR7- and virus dose-dependent mechanism.     

Effect of <Emphasis Type="Italic">Myracrodruon urundeuva</Emphasis> leaf lectin on survival and digestive enzymes of <Emphasis Type="Italic">Aedes aegypti</Emphasis> larvae

Aedes aegypti transmits the viruses that cause yellow and dengue fevers. Vector control is essential, since a vaccine for dengue has not as yet been made available. This work reports on the larvicidal activity of Myracrodruon urundeuva leaf lectin (MuLL) against A. aegypti fourth-stage larvae (L₄). Also, the resistance of MuLL to digestion by L₄ gut proteases and the effects of MuLL on protease, trypsin-like and α-amylase activities from L₄ gut were evaluated to determine if lectin remains active in A. aegypti gut and if insect enzyme activities can be modulated by MuLL. MuLL promoted mortality of L₄ with LC₅₀ of 0.202 mg/ml. Haemagglutinating activity of MuLL was detected even after incubation for 96 h with L₄ gut preparation containing protease activity. MuLL affected the activity of gut enzymes, inhibiting protease and trypsin activities and stimulating α-amylase activity. The results suggest that MuLL may become a new biodegradable larvicidal agent for dengue control. Larvicidal activity of MuLL may be linked to its resistance to proteolysis by larval enzymes and interference in the activity of digestive larval enzymes.