RT Journal Article
T1 Kappa-Opioid Receptor Blockade Ameliorates Obesity Caused by Estrogen Withdrawal via Promotion of Energy Expenditure through mTOR Pathway.
A1 Romero-Pico, Amparo
A1 Novelle, Marta G
A1 Al-Massadi, Omar
A1 Beiroa, Daniel
A1 Tojo, Marta
A1 Heras, Violeta
A1 Ruiz-Pino, Francisco
A1 Senra, Ana
A1 Lopez, Miguel
A1 Blouet, Clemence
A1 Tena-Sempere, Manuel
A1 Nogueiras, Ruben
A1 Dieguez, Carlos
K1 Energy expenditure
K1 Estrogens
K1 Kappa-opioid
K1 Obesity
K1 p70S6K
AB Weight gain is a hallmark of decreased estradiol (E2) levels because of menopause or following surgical ovariectomy (OVX) at younger ages. Of note, this weight gain tends to be around the abdomen, which is frequently associated with impaired metabolic homeostasis and greater cardiovascular risk in both rodents and humans. However, the molecular underpinnings and the neuronal basis for these effects remain to be elucidated. The aim of this study is to elucidate whether the kappa-opioid receptor (k-OR) system is involved in mediating body weight changes associated with E2 withdrawal. Here, we document that body weight gain induced by OVX occurs, at least partially, in a k-OR dependent manner, by modulation of energy expenditure independently of food intake as assessed in Oprk1-/-global KO mice. These effects were also observed following central pharmacological blockade of the k-OR system using the k-OR-selective antagonist PF-04455242 in wild type mice, in which we also observed a decrease in OVX-induced weight gain associated with increased UCP1 positive immunostaining in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Remarkably, the hypothalamic mTOR pathway plays an important role in regulating weight gain and adiposity in OVX mice. These findings will help to define new therapies to manage metabolic disorders associated with low/null E2 levels based on the modulation of central k-OR signaling.
PB MDPI
YR 2022
FD 2022-03-11
LK http://hdl.handle.net/10668/21143
UL http://hdl.handle.net/10668/21143
LA en
NO Romero-Picó A, Novelle MG, Al-Massadi O, Beiroa D, Tojo M, Heras V, et al. Kappa-Opioid Receptor Blockade Ameliorates Obesity Caused by Estrogen Withdrawal via Promotion of Energy Expenditure through mTOR Pathway. Int J Mol Sci. 2022 Mar 14;23(6):3118
DS RISalud
RD Apr 17, 2025