Body Iron Stores Increase Hepatic and Serum Lipid in Rats fed a Standard Western Diet

The liver is the major site for lipoprotein processing and iron storage. Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum of chronic liver disorder with progressive factors hypothesized to include impaired hepatic lipid metabolism and oxidative stress. Since iron produces oxidative stress, its excess may lead to lipid peroxidation and hepatocyte damage. We hypothesized that increased hepatic iron in rats fed a western diet would progress NAFLD. We determined the effect of variation in iron on plasma and hepatic lipids and oxidative stress in a rat model without pre-existing liver damage. Rats were fed liquid diets in which 35% of the energy was fat and contained low (STD-), normal (STD) or twice the normal level (STD+) of iron. The STD+ group also received parenteral iron dextran injections. After 5 weeks liver and blood were taken for analysis. Serum cholesterol and non-esterified fatty acids were increased in STD+ compared with STD group. Serum triglyceride in STD+ rats was increased compared with STD-. Histologically the STD+ group showed foci of macrovesicular lipid droplets, whereas hepatic triglyceride was decreased in STD-. Liver expression of lipid responsive gene (SREBP-2, SREBP-1c, HMG CoA reductase, 7α hydroxylase, MTTP1), chemokine (MCP-1) and oxidative stress marker, haemoxygenase-1 mRNA were similar in all groups. There were significant increases in hepatic malondialdehyde and hydroxyalkenal in STD+ compared with STD group. The erythrocytes of STD+ were osmotically fragile compared with the STD group. Increased liver iron affects plasma and hepatic lipids and may progress NAFLD by impairing hepatic fat metabolism

Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning.

This study used functional magnetic resonance imaging to examine the effects of acute tryptophan (TRP) depletion (ATD), a well-recognized method for inducing transient cerebral serotonin depletion, on brain activity during probabilistic reversal learning. Twelve healthy male volunteers received a TRP-depleting drink or a balanced amino-acid drink ( placebo) in a double-blind crossover design. At 5 h after drink ingestion, subjects were scanned while performing a probabilistic reversal learning task and while viewing a flashing checkerboard. The probabilistic reversal learning task enabled the separate examination of the effects of ATD on behavioral reversal following negative feedback and negative feedback per se that was not followed by behavioral adaptation. Consistent with previous findings, behavioral reversal was accompanied by significant signal change in the right ventrolateral prefrontal cortex (PFC) and the dorsomedial prefrontal cortex. ATD enhanced reversal-related signal change in the dorsomedial PFC, but did not modulate the ventrolateral PFC response. The ATD-induced signal change in the dorsomedial PFC during behavioral reversal learning extended to trials where subjects received negative feedback but did not change their behavior. These data suggest that ATD affects reversal learning and the processing of aversive signals by modulation of the dorsomedial PFC