RESUMO
Today enormous research efforts are being focused on alleviating the massive, adverse effects of obesity. Short peptides are key targets for research as they can be generated from natural proteins, like milk. Here we conducted trypsinogen digestion of beta-lactoglobulin (ß-lg), the major mammalian milk protein, to release the hexamer VY6. It was assayed in vivo for its activities on lipid metabolism using zebra fish as a vertebrate model. Zebra fish juveniles were injected with two different doses of the peptide: 100 and 800 µg per g fish and left for 5 days before sacrificing. Lipid measurements showed significant reduction in liver triglycerides and free cholesterol, as well as increased liver HDL cholesterol. Dose-dependent increases of the mRNA levels of the genes coding for the enzymes acyl coenzyme A oxidase 1 (acox1) and lipoprotein lipase (lpl) were also found. The complete results suggest significant anti-obesity activity of the ß-lg-derived VY6 peptide. Its use as a nutraceutical has been discussed.
Assuntos
Lactoglobulinas/administração & dosagem , Fígado/metabolismo , Obesidade/tratamento farmacológico , Peptídeos/administração & dosagem , Peixe-Zebra/metabolismo , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Animais , Bovinos , Colesterol/metabolismo , HDL-Colesterol/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Lactoglobulinas/química , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Fígado/efeitos dos fármacos , Masculino , Obesidade/enzimologia , Obesidade/genética , Obesidade/metabolismo , Peptídeos/química , Triglicerídeos/metabolismoRESUMO
Growth factors in vertebrates display daily rhythms, which, while widely described in mammals, are still poorly understood in teleost fish. Here, we investigated the existence of daily rhythms in the somatotropic axis of the flatfish Solea senegalensis. In a first experiment, daily rhythms of the expression of pituitary adenylate cyclase-activating polypeptide (pacap), growth hormone (gh), insulin-like growth factor 1 (igf1) and its receptor (igf1r) were analyzed under a 12:12 h light:dark cycle. All genes displayed daily rhythms with the acrophases of pacap, gh and igf1 located in the second half of the dark phase (ZT 20:28-0:04 h), whereas the acrophase of igf1r was located around mid-light (ZT 5:33 h). In a second experiment, the influence of the time of day (mid-light, ML, versus mid-darkness, MD) of GH administration on the expression of these factors and on plasma glucose levels was tested. The response observed depended on the time of injection: the strongest effects were observed at MD, when GH administration significantly reduced pituitary gh and enhanced liver igf1 expression. These results provide the first evidence of daily rhythms and differential day/night effects in growth factors in S. senegalensis, suggesting new insights for investigating the physiology of growth and possible applications to improve fish aquaculture.
Assuntos
Relógios Circadianos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Proteínas de Peixes/metabolismo , Linguados/metabolismo , Hormônio do Crescimento/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proteínas de Peixes/genética , Linguados/genética , Hormônio do Crescimento/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Fotoperíodo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptor IGF Tipo 1/metabolismo , Fatores de TempoRESUMO
The role of insulin-like growth factor 1 (IGF-1) on regulation of growth hormone (GH) and prolactin (PRL) as well as the possible involvement of IGF-1 receptor subtype a (IGF-1Ra) mRNA was assessed in juvenile specimens of Sparus aurata. IGF-1Ra was successfully cloned, and active receptor domains were localized in its mRNA precursor. Also, phylogenetic analysis of the protein sequence indicated a closer proximity to IGF-1Ra isoform found in zebrafish and other teleosts, than to the isoform IGF-1Rb. The most abundant presence of IGF-1Ra mRNA was detected in white muscle, whereas head kidney showed the lowest gene expression among 24 different studied tissues. Pituitaries of juvenile specimens of S. aurata were incubated in vitro with different doses of IGF-1 (0, 1, 100, and 1000 ng mL(-1)) during a period of 10 h. Total RNA with a high quality could be obtained from these pituitaries. PRL mRNA expression significantly increased with increasing IGF-1 doses. Similarly, IGF-1Ra mRNA increased its expression in response to IGF-1. However, GH mRNA levels decreased in a dose-dependent manner after IGF-1 treatment. The contradictory responses of GH and PRL expressions to IGF-1 in our experiment are possibly mediated by IGF-1Ra presence on the somatotrophs and prolactotrophs. The increase in IGF-1Ra mRNA levels may be related to the proper activation of the PI3-K/Akt signal transduction pathways which are normally involved in GH and PRL regulation.
