The fenofibrate functions in mammals could be affected by many factors such as dietary nutrient levels and physiological status. However, this phenomenon has not been well studied in fish. The goal of our study was to investigate the effect of dietary protein contents on metabolic regulation of fenofibrate in Nile tilapia. An 8-week experiment was conducted to feed fish with four diets at two protein levels (28 and 38 %) with or without the supplementation of fenofibrate (200 mg/kg body weight per d). After the trial, the body morphometric parameters, plasma biochemical parameters and quantitative PCR data were examined. These results showed that fenofibrate significantly reduced the feeding intake and weight gain rate, increased the oxidative stress (increased plasma methane dicarboxylic aldehyde) and liver : body ratio (increased hepatosomatic index) in the low protein (LP)-fed fish. In contrast, fenofibrate exhibited a lipid-lowering (reduced hepatic lipid) effect and up-regulated the expressions of the genes related to lipid catabolism, transport and anabolic metabolism in the high protein (HP)-fed fish. The present study suggested that lipid-lowering effect of fenofibrate would be strengthened in the fish fed with the HP diet containing high energy, but in the fish fed with the LP diet containing low energy, the fenofibrate treatment would cause adverse effects for metabolism. Taking together, our study showed that the metabolic regulation of fenofibrate in Nile tilapia was dependent not only on feed energy content but also on dietary nutrient composition, such as dietary protein and/or lipid levels.

Hyperlipidaemia is a major cause of atherosclerosis and related CVD and can be prevented with natural substances. Previously, we reported that a novel Bacillus-fermented green tea (FGT) exerts anti-obesity and hypolipidaemic effects. This study further investigated the hypotriglyceridaemic and anti-obesogenic effects of FGT and its underlying mechanisms. FGT effectively inhibited pancreatic lipase activity in vitro (IC50, 0·48 mg/ml) and ameliorated postprandial lipaemia in rats (26 % reduction with 500 mg/kg FGT). In hypertriglyceridaemic hamsters, FGT administration significantly reduced plasma TAG levels. In mice, FGT administration (500 mg/kg) for 2 weeks augmented energy expenditure by 22 % through the induction of plasma serotonin, a neurotransmitter that modulates energy expenditure and mRNA expressions of lipid metabolism genes in peripheral tissues. Analysis of the gut microbiota showed that FGT reduced the proportion of the phylum Firmicutes in hamsters, which could further contribute to its anti-obesity effects. Collectively, these data demonstrate that FGT decreases plasma TAG levels via multiple mechanisms including inhibition of pancreatic lipase, augmentation of energy expenditure, induction of serotonin secretion and alteration of gut microbiota. These results suggest that FGT may be a useful natural agent for preventing hypertriglyceridaemia and obesity.

We investigated whether the hypolipidaemic effect of fenofibrate and fasting observed in most omnivorous mammals may also apply to herbivorous fish. Grass carp (Ctenopharyngodon idella) fed a high-fat (8 %) diet exhibited a marked increase in blood lipids and body fat after 6 weeks. They were then treated with fenofibrate (100 mg/kg body weight) in the same high-fat diet for 2 weeks, followed by fasting for 1 week. Plasma lipid concentration, body fat amount, fatty acid composition, plasma thiobarbituric acid-reactive substances and some parameters related to hepatic fatty acid oxidation were measured, and liver samples were stained for histological examination. Fenofibrate treatment decreased TAG and cholesterol concentrations in plasma, total lipids of the whole body and liver, and EPA and DHA contents in tissues. Further, a mobilisation of mesenteric fat concomitant with an increase in hepatic peroxisomal fatty acid oxidation and lipid peroxidation was observed. Compared with fenofibrate treatment, fasting decreased body weight and plasma TAG, but not plasma cholesterol. It also reduced the fat content of the whole body and increased the EPA and DHA contents in the liver and other tissues. Fatty acid oxidation was stimulated by fasting in mitochondria, but not in peroxisomes. These data suggest that fenofibrate and fasting regulate the lipid metabolism in grass carp through different metabolic pathways. The grass carp is moderately responsive to a fibrate derivative in comparison with the well-known excess responsiveness of the rat model, and so it could be used for the study of lipid abnormalities as a herbivorous model.