The 11th edition of the IBSA Foundation fellowship program had a record number of projects received. A total of 248 applicants from over 50 countries.
Cintia Folgueira was awarded in Endocrinology with 32,000 € for her project Exploring new insights into brown adipose tissue mitochondria for protection against endocrine disorders. She will investigate valuable insights into prospective therapeutic targets for addressing obesity and related metabolic disorders, particularly by underscoring that the absence of mitochondrial proteins correlates with improvements in obesity, adiposity, and glucose tolerance.
The winner for the area “Endocrinology”, Cintia Folgueira Cobos.
Un estudio del equipo de Guadalupe Sabio en el CNIO, publicado en EMBO Reports, revela el papel crucial de la señalización de la quinasa p38 en células T tanto en la inflamación crónica asociada a la obesidad como en el funcionamiento del tejido adiposo.
Vítor Ferreira, Cintia Folgueira, Ángela Montes-San Lorenzo, Andrea Rodríguez-López, Eva Gonzalez-Iglesias, Pablo Zubiaur, Francisco Abad-Santos, Guadalupe Sabio, Patricia Rada & Ángela M Valverde.
Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS).
Olanzapine reduces body weight exclusively in ovariectomized mice (Image: Cintia Folgueira).
Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17β-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons.
These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.
