Unraveling the role of p38alfa on the control of energy homeostasis and its implications in metabolic disorders.
Authorship
A.A.G.
Máster Universitario en Neurociencia (2ª ed)
A.A.G.
Máster Universitario en Neurociencia (2ª ed)
Defense date
07.18.2025 11:55
07.18.2025 11:55
Summary
The kinase p38alfa is involved in multiple cellular processes, including the regulation of energy metabolism. Previous studies by the group analyzed its function in the arcuate nucleus (ARC) of the hypothalamus, a key region for the control of energy homeostasis, food intake, and glucose metabolism. To this end, p38alfa was deleted in the two main neuronal populations present in the ARC nucleus, AgRP neurons and POMC neurons. It was found that deletion in POMC neurons causes a loss of body weight, whereas deletion of p38alfa in AgRP neurons causes an increase in body weight in mice. This suggests a differential regulation of body metabolism depending on the neuronal type where p38alfa is deleted, highlighting the relevance of studying in depth the physiological implications of this kinase. The present work focused on analyzing the peripheral consequences and the relationship between the deletion of p38alfa in AgRP neurons in mice fed a standard diet, and its influence on metabolically relevant tissues such as the liver, white adipose tissue (WAT), and brown adipose tissue (BAT). To this end, the three tissues were studied from a histological point of view, but the expression of proteins related to thermogenesis, such as UCP1 (Uncoupling Protein 1), and proteins related to hepatic lipolysis, such as LPL (lipoprotein lipase), were also analyzed using Western blot and q-PCR techniques. Morphologically, an increase in adipocyte size was observed in WAT, BAT, and liver in those mice in which p38alfa was deleted in AgRP neurons. Regarding the evaluation of a possible decrease in thermogenesis as a possible explanation for the weight gain in these animals, no significant differences were found in BAT, and a trend toward reduced expression of UCP1 in WAT was observed. At the hepatic level, an increase in lipid accumulation was detected, confirmed by specific staining and accompanied by an alteration in the expression of FGF21 (Fibroblast Growth Factor 21), suggesting a possible metabolic compensation pathway mediated by it. In short, this work delved into the mechanisms of intertissue communication mediated by p38alfa in the hypothalamus, and its role in the regulation of metabolism, to contribute to the understanding of the pathophysiology of obesity
The kinase p38alfa is involved in multiple cellular processes, including the regulation of energy metabolism. Previous studies by the group analyzed its function in the arcuate nucleus (ARC) of the hypothalamus, a key region for the control of energy homeostasis, food intake, and glucose metabolism. To this end, p38alfa was deleted in the two main neuronal populations present in the ARC nucleus, AgRP neurons and POMC neurons. It was found that deletion in POMC neurons causes a loss of body weight, whereas deletion of p38alfa in AgRP neurons causes an increase in body weight in mice. This suggests a differential regulation of body metabolism depending on the neuronal type where p38alfa is deleted, highlighting the relevance of studying in depth the physiological implications of this kinase. The present work focused on analyzing the peripheral consequences and the relationship between the deletion of p38alfa in AgRP neurons in mice fed a standard diet, and its influence on metabolically relevant tissues such as the liver, white adipose tissue (WAT), and brown adipose tissue (BAT). To this end, the three tissues were studied from a histological point of view, but the expression of proteins related to thermogenesis, such as UCP1 (Uncoupling Protein 1), and proteins related to hepatic lipolysis, such as LPL (lipoprotein lipase), were also analyzed using Western blot and q-PCR techniques. Morphologically, an increase in adipocyte size was observed in WAT, BAT, and liver in those mice in which p38alfa was deleted in AgRP neurons. Regarding the evaluation of a possible decrease in thermogenesis as a possible explanation for the weight gain in these animals, no significant differences were found in BAT, and a trend toward reduced expression of UCP1 in WAT was observed. At the hepatic level, an increase in lipid accumulation was detected, confirmed by specific staining and accompanied by an alteration in the expression of FGF21 (Fibroblast Growth Factor 21), suggesting a possible metabolic compensation pathway mediated by it. In short, this work delved into the mechanisms of intertissue communication mediated by p38alfa in the hypothalamus, and its role in the regulation of metabolism, to contribute to the understanding of the pathophysiology of obesity
Direction
MUÑOZ PATIÑO, ANA MARIA (Tutorships)
FOLGUEIRA COBOS, CINTIA (Co-tutorships)
MUÑOZ PATIÑO, ANA MARIA (Tutorships)
FOLGUEIRA COBOS, CINTIA (Co-tutorships)
Court
Rodriguez Diaz, Miguel Angel (Coordinator)
Rivadulla Fernández, Juan Casto (Chairman)
ADRIO FONDEVILA, MARIA FATIMA (Secretary)
RODRIGUEZ PALLARES, JANNETTE (Member)
Rodriguez Diaz, Miguel Angel (Coordinator)
Rivadulla Fernández, Juan Casto (Chairman)
ADRIO FONDEVILA, MARIA FATIMA (Secretary)
RODRIGUEZ PALLARES, JANNETTE (Member)