Effect of neoadjuvant chemotherapy in hepatic steatosis.

UNLABELLED: Chemotherapy drugs often produce side effects in the liver. In recent years, there has been speculation about the ability to produce hepatic steatosis in patients treated with 5-fluorouracil and oxaliplatin. This prospective study examines whether these drugs can produce steatosis in patients with neoadjuvant treatment who were operated on for liver tumors. PURPOSE: Our objective was to assess the effect of neoadjuvant chemotherapy (NAC) on the development of hepatic steatosis in the healthy liver. PATIENTS AND METHODS: This was a prospective study based on 32 patients divided into two groups. The presence of steatosis was assessed using a histological score (Kleiner classification) and a biochemical method (Folch method) for patients from both groups. RESULTS: A total of 14 patients (44%) had hepatic steatosis and half of these were in each group. The steatosis was moderate to severe (grades 2-3) in 4 patients (13%), 2 in each group. The mean levels of triglycerides in the liver were 33.38 and 29.94 mg/g in group I and group II, respectively, with the difference not being statistically significant. CONCLUSIONS: Almost half of the patients treated with NAC for liver neoplasia developed steatosis. Nevertheless, NAC does not seem to increase the risk of hepatic steatosis.

Changes in white adipose tissue metabolism induced by resveratrol in rats.

BACKGROUND: A remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue. METHODS: Sixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography. RESULTS: There was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue. CONCLUSIONS: It can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.

A multi-gene analysis strategy identifies metabolic pathways targeted by trans-10, cis-12-conjugated linoleic acid in the liver of hamsters.

In mice, hepatic functions can be greatly affected by dietary trans-10, cis-12-conjugated linoleic acid (CLA). However, this phenomenon has been less documented in hamsters. In the present study, male hamsters were fed two doses of the trans-10, cis-12-CLA (0.5 and 1%, w/w diet) or linoleic acid (0.5%) for 6 weeks. The effects on the liver were examined by measuring the expression of thirty-six genes representing key metabolic pathways. CLA-responsive genes and their relationships with physiological outcomes were examined by a multivariate analysis procedure. Compared with control hamsters, those receiving either 0.5 or 1% CLA exhibited similar fat loss (15-24%; P < or = 0.05) and liver enlargement (21-28%; P < or = 0.05), with no signs of steatosis. We also observed a dose-dependent increase in the transcription of genes involved in lipid breakdown and lipid harvesting from blood, and in genes related to the oxidative stress and inflammatory responses. These responsive genes varied in parallel with cell membrane lipids (R2 0.31-0.42) and to a lesser extent with liver enlargement (R2 0.22) (all P < 0.05). We conclude that in hamsters, liver enlargement induced by trans-10, cis-12-CLA is accompanied by an increased metabolic potential to process fatty acids from mobilised adipose stores. This elevated metabolic activity, comprised of anabolic pathways and their catabolic counterparts, can trigger inflammation and the oxidant stress defence pathways in a dose-dependent manner. These results provide novel insights into the mechanisms by which trans-10, cis-12-CLA affects pathways related to liver function.

Fluoxetine alters mu opioid receptor expression in obese Zucker rat extrahypothalamic regions.

The aim of this article was to describe the effects of chronic fluoxetine on mu opioid receptor expression in obese Zucker rat extrahypothalamic regions. Male obese Zucker (fa/fa) rats were administered with fluoxetine (10 mg/kg; i.p.) daily for two weeks. Brain regional immunostaining for mu opioid receptor was carried out. An increase in the numbers of neural cells immunostained for mu opioid receptor in caudatus-putamen, dentate gyrus, lateral septum, amygdala, and frontal, parietal, and piriform cortices was observed. Increased mu opioid receptor expression in the central amygdaloid nuclei suggests a decreased opioidergic tone at this level that could be involved in fluoxetine anorectic action.