Inter-organ crosstalk and the regulation of lipid metabolism

Metabolic regulation is a complex and essential process for the survival of multicellular organisms, necessitating the coordination of various cell types and organ systems to adapt to changes in nutrient availability. Stressors, such as fasting, cold exposure, and exercise, further challenge this delicate balance and require efficient inter-organ communication to ensure optimal energy utilization. Adipocytes, as the primary site of energy storage, play a crucial role in providing fatty acids for tissues like the liver during such conditions. The goal of this proposed research is to gain a comprehensive in vivo understanding of the dynamic changes that occur in the liver upon activation of adipocyte lipolysis, with a specific focus on the impact of the glucocorticoid receptor (GR) pathway. This proposed research aims to investigate the intricate metabolic adaptations associated with adipocyte lipolysis and its influence on the glucocorticoid receptor (GR) pathway in the liver. Through a comprehensive in vivo approach, we will explore the impact of adipocyte lipolysis on the Corticotropin-Releasing Hormone (CRH) within the Hypothalamic-Pituitary-Adrenal (HPA) axis and its potential link to stress responses. We will also delve into the role of the hepatic glucocorticoid receptor in regulating fat oxidation and ketogenesis, crucial processes for energy utilization. Additionally, we will investigate whether the induction of Plin5 expression by GR activation promotes ketogenesis by facilitating interactions between mitochondria and lipid droplets. This proposal will also implement a learning module to train students in genetic engineering and teach them about CRISPR-Cas9 system used for biomedical research. The research seeks to advance our understanding of these intricate metabolic pathways and provide insights into stress-related metabolic regulation, with potential implications for therapeutic interventions in metabolic disorders. Project Number: 1R01GM154435-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Claudio Villanueva | Institution: UNIVERSITY OF CALIFORNIA LOS ANGELES, LOS ANGELES, CA | Award Amount: $533,171 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 CDPT-K (50)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11073575