| Title: |
Glucagon regulates the stability of REV-ERBα to modulate hepatic glucose production in a model of lung cancer–associated cachexia |
| Authors: |
Verlande, Amandine; Chun, Sung Kook; Goodson, Maggie O; Fortin, Bridget M; Bae, Hosung; Jang, Cholsoon; Masri, Selma |
| Source: |
Science Advances, vol 7, iss 26 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2021 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
Biochemistry and Cell Biology; Biological Sciences; Liver Disease; Lung Cancer; Rare Diseases; Digestive Diseases; Lung; Cancer; Nutrition; Cachexia; 2.1 Biological and endogenous factors; 1.1 Normal biological development and functioning; Adenocarcinoma of Lung; Animals; Circadian Rhythm; Glucagon; Glucose; Liver; Lung Neoplasms; Mice; Nuclear Receptor Subfamily 1; Group D; Member 1 |
| Description: |
Lung adenocarcinoma is associated with cachexia, which manifests as an inflammatory response that causes wasting of adipose tissue and skeletal muscle. We previously reported that lung tumor-bearing (TB) mice exhibit alterations in inflammatory and hormonal signaling that deregulate circadian pathways governing glucose and lipid metabolism in the liver. Here, we define the molecular mechanism of how de novo glucose production in the liver is enhanced in a model of lung adenocarcinoma. We found that elevation of serum glucagon levels stimulates cyclic adenosine monophosphate production and activates hepatic protein kinase A (PKA) signaling in TB mice. In turn, we found that PKA targets and destabilizes the circadian protein REV-ERBα, a negative transcriptional regulator of gluconeogenic genes, resulting in heightened de novo glucose production. Together, we identified that glucagon-activated PKA signaling regulates REV-ERBα stability to control hepatic glucose production in a model of lung cancer-associated cachexia. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt70r5f17w; https://escholarship.org/uc/item/70r5f17w; https://escholarship.org/content/qt70r5f17w/qt70r5f17w.pdf |
| DOI: |
10.1126/sciadv.abf3885 |
| Availability: |
https://escholarship.org/uc/item/70r5f17w; https://escholarship.org/content/qt70r5f17w/qt70r5f17w.pdf; https://doi.org/10.1126/sciadv.abf3885 |
| Rights: |
CC-BY-NC |
| Accession Number: |
edsbas.4F34613A |
| Database: |
BASE |