Abstract
Various pathophysiological situations of negative energy balance involve the intense depletion of the body’s energy reserves. White adipose tissue is a central place to store energy and a major endocrine organ. As a model of choice to better understand how the white adipose tissue dynamically responds to changes in substrate availability, we used the prolonged fasting paradigm, which is characterized by successive periods of stimulated (phase 2) and then reduced (phase 3) lipid mobilization/utilization. Using omics analyses, we report a regulatory transcriptional program in rat epididymal (EPI) adipose tissue favoring lipolysis during phase 2 and repressing it during phase 3. Changes in gene expression levels of lipases, lipid droplet-associated factors, and the proteins involved in cAMP-dependent and cAMP-independent regulation of lipolysis are highlighted. The mRNA and circulating levels of adipose-secreted factors were consistent with the repression of insulin signaling during prolonged fasting. Other molecular responses are discussed, including the regulation of leptin and adiponectin levels, the specific changes reflecting an increased fibrinolysis and a possible protein catabolism-related energy saving mechanism in late fasting. Finally, some differences between internal and subcutaneous (SC) adipose tissues are also reported. These data provide a comprehensive molecular basis of adipose tissue responses when facing a major energetic challenge.
Funding source: Agence Nationale de la Recherche
Award Identifier / Grant number: ANR-05-BLAN-0069
Funding statement: This work was supported by the Agence Nationale de la Recherche (Funder Id: http://dx.doi.org/10.13039/501100001665, Programme Proteonutr ANR-05-BLAN-0069) and the French Proteomic Infrastructure (ProFI; ANR-10-INSB-08-03). During the tenure of this study, TW was supported by the Centre National de la Recherche Scientifique (CNRS) and the Bruker Daltonics Company. Technical assistance from Chrystel Husser and Dr. JM Strub was essential to DIGE experiment and plasma profiling, respectively. We also thank Drs. Christelle Thibault-Carpentier, Doulaye Dembele and Violaine Alunni for involvement in transcriptomics experiments, and Dr. Patrick Guterl for bioinformatics assistance in functional annotation analysis.
Conflict of interest statement: The authors declare no competing financial interests.
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The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2019-0184).
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