Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver
| Autor: | Paola Merlo, Rajat Singh, Marina García-Macia, Emily Liebling, Nuria Martinez-Lopez, Francesco Cecconi, Gary J. Schwartz, Srabani Sahu, Diana Athonvarangkul |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Autophagosome Male medicine.medical_specialty Pro-Opiomelanocortin Physiology Transgene Lipolysis Molecular Sequence Data Hypothalamus Adipose tissue Mice Transgenic Article 03 medical and health sciences Oxygen Consumption Proopiomelanocortin Adipose Tissue Brown Internal medicine Lipid droplet Brown adipose tissue medicine Autophagy Animals Amino Acid Sequence Molecular Biology Neurons biology Lipase Lipid Droplets Cell Biology Cold Temperature Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Adipocytes Brown Liver biology.protein Female Lysosomes Microtubule-Associated Proteins |
| Zdroj: | Cell Metabolism. 23(1):113-127 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2015.10.008 |
| Popis: | The integrative physiology of inter-organ communication in lipophagy regulation is not well understood. Lipophagy and the cytosolic lipases ATGL and HSL contribute to lipid droplet (LD) mobilization; however, whether autophagy proteins engage with lipases to promote lipid utilization remains unknown. Here, we show that cold induces autophagy in proopiomelanocortin (POMC) neurons and activates lipophagy in brown adipose tissue (BAT) and liver in mice. Targeted activation of autophagy in POMC neurons via intra-hypothalamic rapamycin is sufficient to trigger lipid utilization in room temperature-housed mice. Conversely, inhibiting autophagy in POMC neurons or in peripheral tissues or denervating BAT blocks lipid utilization. Unexpectedly, the autophagosome marker LC3 is mechanistically coupled to ATGL-mediated lipolysis. ATGL exhibits LC3-interacting region (LIR) motifs, and mutating a single LIR motif on ATGL displaces ATGL from LD and disrupts lipolysis. Thus, cold-induced activation of central autophagy activates lipophagy and cytosolic lipases in a complementary manner to mediate lipolysis in peripheral tissues. |
| Databáze: | OpenAIRE |
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