Mitohormesis in hypothalamic POMC neurons mediates regular exercise-induced high-turnover metabolism

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• Alternative Title:
  Cell Metab
• Personal Author:
  Kang, Gil Myoung ; Min, Se Hee ; Lee, Chan Hee ; Kim, Ji Ye ; Lim, Hyo Sun ; Choi, Min Jeong ; Jung, Saet-Byel ; Park, Jae Woo ; Kim, Seongjun ; Park, Chae Beom ; Dugu, Hong ; Choi, Jong Han ; Jang, Won Hee ; Park, Se Eun ; Cho, Young Min ; Kim, Jae Geun ; Kim, Kyung-Gon ; Choi, Cheol Soo ; Kim, Young-Bum ; Lee, Changhan ; Shong, Minho ; Kim, Min-Seon
• Description:
  Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPR|) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-END expression and induces adipose tissue UPR| and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.
• Subjects:
  Animals Cell Line, Tumor Energy Metabolism Hypothalamus Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mitochondria Neurons Physical Conditioning, Animal Pro-Opiomelanocortin

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• Keywords:
  Adipose Alzheimer's Disease Alzheimer's Disease Sequencing Project Antiviral Agents Crif1 Exercise Herpes Simplex Human Papillomavirus Hypothalamus Metabolism Mitochondria Mitohormesis MOTS-c Obesity Proopiomelanocortin Ribosome Stress Thermogenesis Torque Teno Viruses Whole Exome Sequencing Whole Genome Sequencing β-endorphin

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• Source:
  Cell Metab. 33(2):334-349.e6
• Pubmed ID:
  33535098
• Pubmed Central ID:
  PMC7959183
• Document Type:
  Journal Article
• Funding:
  H23 IP000855/IP/NCIRD CDC HHSUnited States/ ; R01 AG052558/AG/NIA NIH HHSUnited States/ ; R01 DK123002/DK/NIDDK NIH HHSUnited States/ ; R01 GM136837/GM/NIGMS NIH HHSUnited States/
• Volume:
  33
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:1f01382cf73d8e9f0dd6f98b1cf941bdda495e9c3046fc9e41b35f209da15fa8d09d494fdbccfeaeefdcc48b583716f57a56c26a3fffdc9b29771fac0d8e356e
• Download URL:
  https://stacks.cdc.gov/view/cdc/113970/cdc_113970_DS1.pdf
• File Type:
  [PDF - 3.93 MB ]