BACKGROUND AND PURPOSE The lack of safe and effective treatments for obesity has increased interest in natural products that may serve as alternative therapies. From this perspective, we have analysed the effects of daidzein, one of the main soy isoflavones, on diet‐induced obesity in rats. EXPERIMENTAL APPROACH Rats made obese after exposure to a very (60%) high fat‐content diet were treated with daidzein (50 mg·kg−1) for 14 days. The dose was selected on the basis of the acute effects of this isoflavone on a feeding test. After 14 days, animals were killed and plasma, white and brown adipose tissue, muscle and liver studied for the levels and expression of metabolites, proteins and genes relevant to lipid metabolism. KEY RESULTS A single treatment (acute) with daidzein dose‐dependently reduced food intake. Chronic treatment (daily for 14 days) reduced weight gain and fat content in liver, accompanied by high leptin and low adiponectin levels in plasma. While skeletal muscle was weakly affected by treatment, both adipose tissue and liver displayed marked changes after treatment with daidzein, affecting transcription factors and lipogenic enzymes, particularly stearoyl coenzyme A desaturase 1, a pivotal enzyme in obesity. Expression of uncoupling protein 1, an important enzyme for thermogenesis, was increased in brown adipose tissue after daidzein treatment. CONCLUSIONS AND IMPLICATIONS These results support the use of isoflavones in diet‐induced obesity, especially when hepatic steatosis is present and open a new field of use for these natural products.

The ECS (endocannabinoid system) plays an important role in the onset of obesity and metabolic disorders, implicating central and peripheral mechanisms predominantly via CB1 (cannabinoid type 1) receptors. CB1 receptor antagonist/inverse agonist treatment improves cardiometabolic risk factors and insulin resistance. However, the relative contribution of peripheral organs to the net beneficial metabolic effects remains unclear. In the present study, we have identified the presence of the endocannabinoid signalling machinery in skeletal muscle and also investigated the impact of an HFD (high-fat diet) on lipid-metabolism-related genes and endocannabinoid-related proteins. Finally, we tested whether administration of the CB1 inverse agonist AM251 restored the alterations induced by the HFD. Rats were fed on either an STD (standard/low-fat diet) or an HFD for 10 weeks and then treated with AM251 (3 mg/kg of body weight per day) for 14 days. The accumulated caloric intake was progressively higher in rats fed on the HFD than the STD, resulting in a divergence in body weight gain. AM251 treatment reduced accumulated food/caloric intake and body weight gain, being more marked in rats fed on the HFD. CB2 (cannabinoid type 2) receptor and PPARα (peroxisome-proliferator-activated receptor α) gene expression was decreased in HFD-fed rats, whereas MAGL (monoglyceride lipase) gene expression was up-regulated. These data suggest an altered endocannabinoid signalling as a result of the HFD. AM251 treatment reduced CB2 receptor, PPARγ and AdipoR1 (adiponectin receptor 1) gene expression in STD-fed rats, but only partially normalized the CB2 receptor in HFD-fed rats. Protein levels corroborated gene expression results, but also showed a decrease in DAGL (diacylglycerol) β and DAGLα after AM251 treatment in STD- and HFD-fed rats respectively. In conclusion, the results of the present study indicate a diet-sensitive ECS in skeletal muscle, suggesting that blockade of CB1 receptors could work towards restoration of the metabolic adaption imposed by diet.

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BACKGROUND AND PURPOSEPeripheral blockade of cannabinoid CB1 receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects of centrally acting CB1 receptor antagonists. In this study we analysed the effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist with poor brain penetration, in an animal model of diet-induced obesity. EXPERIMENTAL APPROACHTo induce obesity, male Wistar rats were fed a high-fat diet (HFD; 60 kcal% fat) whereas controls received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding, animals received a daily i.p. injection of vehicle or 3 mg·kg -1 LH-21 for 10 days. Plasma and liver samples were used for biochemical analyses whereas visceral fat-pad samples were analysed for lipid metabolism gene expression using real-time RT-PCR. In addition, the potential of LH-21 to interact with hepatic cytochrome P450 isoforms and cardiac human Ether-à-go-go Related Gene (hERG) channels was evaluated. KEY RESULTSLH-21 reduced feeding and body weight gain in HFD-fed animals compared with the control group fed SD. In adipose tissue, this effect was associated with decreased gene expression of: (i) leptin; (ii) lipogenic enzymes, including SCD-1; (iii) CB1 receptors; and (iv) both PPARa and PPARg. Although there were no significant differences in plasma parameters between HFDand SD-fed rats, LH-21 did not seem to induce hepatic, cardiac or renal toxicity. CONCLUSIONS AND IMPLICATIONSThese results support the hypothesis that treatment with the peripherally neutral acting CB1 receptor antagonist, LH-21, may promote weight loss through modulation of visceral adipose tissue. AbbreviationsCYP, cytochrome P450; FAME, fatty acid methyl esters; hERG, Ether-à-go-go Related Gene; HFD, high fat diet; LH-21, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole; SD, standard diet BJP British Journal of Pharmacology

The study is an attempt to evaluate the feasibility of intensive tench culture using non-specific diets as a preliminary step to check the acclimatization of the species under intensive rearing systems. Five-month-old juvenile tench were reared in recirculating systems at mean water temperatures of 22°C for 75 days. Fish fed with four different commercial diets (trout starter, trout first feeding, sea-bass and eel), showed significantly higher final weights than the fish fed either eel or sea-bass diets. Initial weight for all treatments was 2.3 ± 0.53 g. Final weight for the commercial diet groups was 3.56 ± 0.4 g, compared with the remaining groups that reached 2.09 ± 0.47 g (P < 0.05). Significantly higher survival rates were observed in the eel and sea-bass groups (84.7 and 51.5%, respectively) than in either of the trout diet groups (38%). Specific growth rates (1.26 vs -0.18) and condition factor (1.26 vs 0.93) were also higher than those fed with salmonid diets (P < 0.05). Results obtained in this study indicate that regardless of the speciesÕ slow growth, when compared with other cyprinids, final growth rates and survival of tench fed exclusively on sea-bass or eel diets can be considered satisfactory. It must be pointed out that these promising results were obtained at lower temperatures than previous studies of tench in culture systems. The use of belt feeders did not show improvement in growth compared with manually fed fish when trout diets were used.