Percorrer por autor "Rotllant, Josep"
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- Agouti overexpression in a transgenic model regulates integrity, permeability and electrogenic amino acid transport in zebrafish intestinePublication . Leal, Esther; Angotzi, Anna Rita; Godino-Gimeno, Alejandra; Gregorio, Silvia F.; Rotllant, Josep; Saera-Vila, Alfonso; Fuentes, Juan; Cerdá-Reverter, José MiguelOverexpression of asip1 in transgenic zebrafish disrupts dorsoventral pigment pattern in addition to increasing food intake levels and linear growth. A higher feed intake is unnecessary in transgenic fish to enable larger and heavier growth. A plausible explanation may rely on the enhanced feeding efficiency mediated by improved nutrient absorption in transgenic animals. To test this hypothesis, wide scope transcriptomic techniques were used to elucidate the potential pathways involved in the enhanced nutrient absorption and intestinal epithelium permeability/integrity. In addition, the electrogenic capacity for amino acid transport was analysed. Transcriptomic analysis reveal that amino acid, monocarboxylates, ionic and vitamin transmembrane transporters were substantially modified. Enrichment analysis also revealed an inhibition of intestinal lipid metabolism and down-regulation of KEGG pathways related to membrane integrity suggesting augmented intestinal laxity that may enhance paracellular transport. Electrophysiological experiments carried out in Ussing chambers show that asip1 overexpression decrease membraned tissue resistance (Rt), indicating a modification of the intestinal barrier function in ASIP1 transgenic animals. Similarly, paracellular permeability was higher in transgenic zebrafish. Both the decrease in Rt and the increase in permeability point to an ASIP1-dependent decrease in the tissue barrier function. Electrogenic amino acid transport was also enhanced in transgenic animals providing strong indication that ASIP1 fish can extract more amino acids from their diet at similar feeding levels. Both transcriptomic and electrophysiological results suggest that asip1-overexpressing zebrafish display improved nutrient absorption and by extension a higher feed efficiency which explains enhanced growth in the absence of augmented food intake. The enhanced growth of ASIP1 zebrafish potentially mediated by improved nutrient uptake and feed efficiency suggests that the melanocortin system, specifically asip1 overexpression, is a potential target for the development of genetically engineered fish displaying improved performance and no differential lipid accumulation.
- Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathwayPublication . Suarez-Bregua, Paula; Torres-Nunez, Eva; Saxena, Ankur; Guerreiro, Pedro; Braasch, Ingo; Prober, David A.; Moran, Paloma; Miguel Cerda-Reverter, Jose; Du, Shao Jun; Adrio, Fatima; Power, Deborah M.; Canario, Adelino V. M.; Postlethwait, John H.; Bronner, Marianne E.; Canestro, Cristian; Rotllant, JosepRegulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals' lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle.
- Stress, glucocorticoids and bone: A review from mammals and fishPublication . Suarez-Bregua, Paula; Guerreiro, Pedro M; Rotllant, JosepGlucocorticoids (GCs) are the final effector products of a neuroendocrine HPA/HPI axis governing energy balance and stress response in vertebrates. From a physiological point of view, basal GC levels are essential for intermediary metabolism and participate in the development and homeostasis of a wide range of body tissues, including the skeleton. Numerous mammalian studies have demonstrated that GC hormones exert a positive role during bone modeling and remodeling as they promote osteoblastogenesis to maintain the bone architecture. Although the pharmacological effect of the so-called stress hormones has been widely reported, the role of endogenous GCs on bone mineral metabolism as result of the endocrine stress response has been largely overlooked across vertebrates. In addition, stress responses are variable depending on the stressor (e.g., starvation, predation, and environmental change), life cycle events (e.g., migration and aging), and differ among vertebrate lineages, which react differently according to their biological, social and cognitive complexity (e.g., mineral demands, physical, and psychological stress). This review intends to summarize the endogenous GCs action on bone metabolism of mammals and fish under a variety of challenging circumstances. Particular emphasis will be given to the regulatory loop between GCs and the parathyroid hormone (PTH) family peptides, and other key regulators of mineral homeostasis and bone remodeling in vertebrates.
- Studies on cortisol, corticosterone, and 17b-estradiol indicate these steroids have no role in stress or reproduction in the common octopus (Octopus vulgaris)Publication . Maskrey, Benjamin H.; Costas, Carolina; Méndez-Martínez, Luís; Guerrero-Peña, Laura; Tur, Ricardo; García, Pablo; Touriñan, Pablo; Chavarrias, David; Canario, Adelino; Scott, Alex P.; Rotllant, JosepThe common octopus (Octopus vulgaris) is a promising candidate for aquaculture diversification, particularly in Europe. As interest in octopus farming grows, animal welfare concerns arise. In bony vertebrates (teleosts and tetrapods), measurements of the levels of corticosterone or cortisol have been successfully used as indicators of stress and welfare. Here, it is explored whether octopuses also produce cortisol or corticosterone and, if so, whether they are released into the water in response to stress (as can be done in teleosts and amphibians). The ability of the octopus to absorb cortisol from the water is also investigated-with another steroid, the principle vertebrate estrogen, 17 beta-estradiol (E-2), being used as a positive uptake control. In this study, using liquid chromatography tandem mass spectrometry techniques, it was found that octopus hemolymph did not contain either cortisol, corticosterone, cortisone (a common metabolite of cortisol), or E-2. Nor were any of the corticosteroids consistently found in the water in which stressed octopuses were held. The results support the evolutionary argument that octopuses are unlikely to exhibit a stress response mediated by vertebrate-like corticosteroids. Octopus demonstrated a low ability to absorb cortisol from the water (<2% over 24 h) but showed a high ability to absorb E-2 from water (92% over 24 h). In this latter respect, the octopus is similar to other mollusks. The finding calls into doubt the origin of the E-2 measured in this species. NEW & NOTEWORTHY This study demonstrates that common octopuses (Octopus vulgaris Cuvier 1797) do not produce cortisol, cortisone, or corticosterone in response to stress. Using liquid chromatography tandem mass spectrometry, it was also shown that octopuses have a low absorption rate of cortisol from water but a high absorption rate of 17 beta-estradiol (E2). The findings support the evolutionary argument that octopuses are unlikely to exhibit a stress response mediated by vertebrate-like