RESUMEN
Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 µM, and 1 µM 17ß-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 µM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 µM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout.
Asunto(s)
Adipocitos/efectos de los fármacos , Adipogénesis , Autofagia , Genisteína/farmacología , Fitoestrógenos/farmacología , Trucha/metabolismo , Adipocitos/metabolismo , Animales , Catepsina D/genética , Catepsina D/metabolismo , Supervivencia Celular , Células Cultivadas , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Genisteína/toxicidad , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Metabolismo de los Lípidos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Fitoestrógenos/toxicidadRESUMEN
Fish are rich in n-3 long-chain polyunsaturated fatty acids (LC-PUFA), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, thus they have a great nutritional value for human health. In this study, the adipogenic potential of fatty acids commonly found in fish oil (EPA and DHA) and vegetable oils (linoleic (LA) and alpha-linolenic (ALA) acids), was evaluated in bone-derived mesenchymal stem cells (MSCs) from gilthead sea bream. At a morphological level, cells adopted a round shape upon all treatments, losing their fibroblastic form and increasing lipid accumulation, especially in the presence of the n-6 PUFA, LA. The mRNA levels of the key transcription factor of osteogenesis, runx2 significantly diminished and those of relevant osteogenic genes remained stable after incubation with all fatty acids, suggesting that the osteogenic process might be compromised. On the other hand, transcript levels of the main adipogenesis-inducer factor, pparg increased in response to EPA. Nevertheless, the specific PPARγ antagonist T0070907 appeared to suppress the effects being caused by EPA over adipogenesis. Moreover, LA, ALA and their combinations, significantly up-regulated the fatty acid transporter and binding protein, fatp1 and fabp11, supporting the elevated lipid content found in the cells treated with those fatty acids. Overall, this study has demonstrated that fatty acids favor lipid storage in gilthead sea bream bone-derived MSCs inducing their fate into the adipogenic versus the osteogenic lineage. This process seems to be promoted via different pathways depending on the fatty acid source, being vegetable oils-derived fatty acids more prone to induce unhealthier metabolic phenotypes.