i
Mitohormesis in hypothalamic POMC neurons mediates regular exercise-induced high-turnover metabolism
-
2 02 2021
-
-
Source: Cell Metab. 33(2):334-349.e6
[PDF-3.93 MB]
Details:
-
Alternative Title:Cell Metab
-
Personal Author:
-
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:
-
Keywords:
-
Source:
-
Pubmed ID:33535098
-
Pubmed Central ID:PMC7959183
-
Document Type:
-
Funding:
-
Volume:33
-
Issue:2
-
Collection(s):
-
Main Document Checksum:
-
Download URL:
-
File Type:
