ABSTRACT
Endocrine disrupting (EDs) chemicals can increase or block the metabolism of endogenous peptidergic or steroid hormones by activating or antagonizing nuclear receptors in the hypothalamus, besides adipose tissue, liver and gonads. Toxicological and epidemiological studies have suggested the involvement of different EDs in an increasing number of metabolic disorders such as obesity and diabetes. The aim of this review is to summarize the literature from experimental animal studies demonstrating the impairment of body weight raised by the deregulation of peptidergic signals as well as by the activation of key metabolic molecular targets. Regarding the modification of gene transcription levels induced by EDs, new data on DEHP effect on food intake and lipid metabolism in the experimental model zebrafish (Danio rerio) have also been included in this review providing evidences about the dangerousness of DEHP low doses.
Subject(s)
Endocrine Disruptors/toxicity , Receptors, Cell Surface/drug effects , Animals , Body Weight/drug effects , Diethylhexyl Phthalate/toxicity , Eating/drug effects , Hormones/metabolism , Hypothalamus/drug effects , Hypothalamus/physiology , Lipid Metabolism/drug effects , Metabolic Diseases/etiology , Metabolic Diseases/metabolism , Steroids/metabolism , ZebrafishABSTRACT
The aim of this study was to increase our understanding of the physiological functions controlled by the endocannabinoid system during embryogenesis. Using genomic and proteomic methodologies applied to zebrafish, we proved, for the first time in an oviparous species, that the cannabinoid receptor CB1 is not a maternal factor. The analysis of different developmental stages showed that the zygotic expression of CB1 occurs from the 3 somites stage while CB1 protein becomes evident during hatching time, indicating an involvement in the hatching process. This result was supported by the data regarding embryo exposure to the CB1 antagonist, AM251, consisting in a 75% decrease in hatching rate. In addition, as previously described for mammals, we observed a role of CB1 in the motility behavior in zebrafish larvae.
Subject(s)
Cannabinoid Receptor Modulators/metabolism , Endocannabinoids , Zebrafish/embryology , Animals , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/metabolism , Embryonic Development/drug effects , Female , Gene Expression Regulation, Developmental/drug effects , Locomotion/drug effects , Male , Oogenesis/drug effects , Ovary/drug effects , Ovary/metabolism , Piperidines/pharmacology , Pyrazoles/pharmacology , RNA Transport/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Zebrafish/geneticsABSTRACT
Endocannabinoids are known to be lipidic mediators with several biological functions as the stimulation of food intake and lipid metabolism via cannabinoid receptor CB1. Many evidences, such as the presence of CB1 mRNA in fat tissue, suggest a peripheral role for endocannabinoids in regulating lipogenesis and body weight in mammals. As animal models constitute good tools to study endocannabinoid system dynamics, we analyzed the role of the endocannabinoid anandamide (AEA) in modulating lipid metabolism and growth in zebrafish larvae and adults. The data obtained indicated that AEA administered via water modulates the transcription of its own receptor CB1, besides to up-regulate gene expression of sterol regulatory element binding protein (SREBP) and of the insulin-like growth factors (IGF-1 and IGF-2). The results here obtained represent the first evidence in fish of the endocannabinoid system involvement in lipid metabolism and growth.
Subject(s)
Arachidonic Acids/pharmacology , Lipid Metabolism/drug effects , Polyunsaturated Alkamides/pharmacology , Zebrafish/growth & development , Zebrafish/metabolism , Animals , Endocannabinoids , Gene Expression Regulation, Developmental/drug effects , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Larva/drug effects , Larva/metabolism , Liver/drug effects , Liver/metabolism , Piperidines/pharmacology , Pyrazoles/pharmacology , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Sterol Regulatory Element Binding Proteins/genetics , Sterol Regulatory Element Binding Proteins/metabolism , Zebrafish/geneticsABSTRACT
It is known that heavy metals can accumulate in tissues during aquatic organism growth (bioaccumulation) and often biomagnify up the food chain interfering with the health and reproduction of both wildlife and humans. Recently, cadmium (Cd) was included in the endocrine disruptors list, exerting its effect on gametes quality and reproductive functions; in addition, its role as apoptotic factor was evidenced in different cell types and tissues. In the present study, the effects of two different Cd doses on testis and liver of the black goby Gobius niger were analyzed. Cd concentration in the water and its uptake by the gills were measured by differential pulse anodic stripping voltammetry. Toxic, apoptotic, and stressor Cd effects were analyzed using metallothionein (MTT), caspase 3 and heath shock protein 70 (HSP70), respectively, as bioindicators. The results of the present study suggested that, in the gills, the saturation of all specific metal sites was reached only with the highest Cd dose exposure. Either testis and liver showed an increase of MTT gene expression and protein synthesis in addition to HSP70 gene expression, related with Cd concentration in the water indicating that both tissues were affected by Cd exposure. In conclusion, the present study, not only shows the toxic effect of Cd on hepatic tissue, but also indicates its potency as apoptotic factor in the testis. This is supported by the increase of caspase 3 gene expression and the presence of its active form in testis of exposed fish.
