at the CNIO

Tag: brown adipose tissue (Page 1 of 7)

Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: effects on brown/beige adipose tissues and liver

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.

A combination of a dopamine receptor 2 agonist and a kappa opioid receptor antagonist synergistically reduces weight in diet-induced obese rodents

Beatriz Cicuéndez, Javier Pérez-García & Cintia Folgueira.

As the global obesity rate increases, so does the urgency to find effective anti-obesity drugs. In the search for therapeutic targets, central nervous system (CNS) mechanisms engaged in the regulation of energy expenditure and food intake, such as the opioid and dopamine systems, are crucial.

Increased temperature in a mouse treated with BC and PF-04455242 (Image: Cintia Folgueira).

In this study, we examined the effect on body weight of two drugs: bromocriptine (BC), a D2R receptor agonist, and PF-04455242, a selective κ opioid receptor (KOR) antagonist. Using diet-induced obese (DIO) rats, we aimed to ascertain whether the administration of BC and PF-04455242, independently or in combination, could enhance body weight loss. Furthermore, the present work demonstrates that the peripheral coadministration of BC and PF-04455242 enhances the reduction of weight in DIO rats and leads to a decrease in adiposity in a food-intake-independent manner. These effects were based on heightened energy expenditure, particularly through the activation of brown adipose tissue (BAT) thermogenesis.

Overall, our findings indicate that the combination of BC and PF-04455242 effectively induces body weight loss through increased energy expenditure by increasing thermogenic activity and highlight the importance of the combined use of drugs to combat obesity.

Predoctoral contract in metabolism

We are seeking a highly motivated candidate, who would like to start a scientific career doing their doctoral thesis working in understanding p38 kinases role in how the communiation between organs affect the metabolic. This work will be supervised by Dr. Guadalupe Sabio.

We offer incorporation to CNIC via an FPU predoctoral contract. Interested candidates will need to apply before 19 September 2023 in the following CNIC website:

METABOkines: Comunicación celular en el metabolismo: Implicación de la vía de las p38s.

PID2022-138525OB-I00

ELEGIBILITY CRITERIA

  • This call is open to applicants from all nationalities  holding a Master’s degree in Biomedical Sciences.
  • An excellent academic record and previous research experience during their undergraduate period will be valued very positively.
  • Authorship of publicacions in indexed journal will be valued very positively.
  • Candidates must have a solid working knowledge of English.
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