Hepatic Yap1 activates systemic catabolism and muscle loss during organ repair: evidence for a liver-derived common mechanism with cancer cachexia.
HAMIDI, T.; Yang, Y.; Robinson, T. P.; Kronbergs, A.; Au, E.; Rupert, J. E.; Zhong, X.; Lal, S.; Liang, T.; Robling, A. G.; Hoggatt, A.; Carvalho, R.; Cury, S. S.; Wells, C.; Zimmers, T.; Koniaris, L. G.
Show abstract
Recovery from critical injury concomitant with restoration of functional organ mass invokes a systemic catabolic response leading to muscle and fat loss, known as cachexia. We interrogated this process using mouse models of organ repair, including liver regeneration after hepatectomy, Yap1-mediated hepatomegaly, and pneumonectomy. Both hepatectomy and Yap1 induced systemic catabolism. Muscle and adipose wasting scaled with degree of liver growth, with 10-25% reduction of muscle mass and 50-80% of fat mass. In contrast, non-regenerative lung injury did not induce tissue wasting. Liver growth elevated resting energy expenditure. Tracer studies demonstrated redistribution of muscle-derived cholesterol and amino acids to regenerating liver. Gene expression changes in livers and muscles showed high concordance between the liver growth models and cancer cachexia models, including pancreatic adenocarcinoma cachexia. We propose that cachexia is a normal and essential reparative process in organ repair and regeneration and further, that cancer cachexia is a pathological exacerbation of an adaptive process mediated by activation of Yap1 in the liver.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Liver-innervating vagal sensory neurons play an indispensable role in the development of hepatic steatosis and anxiety-like behavior in mice fed a high-fat diet. 96%
- NAD+ repletion with niacin counteracts cancer cachexia 96%
- Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria 96%
Similar papers in this journal
- β-Catenin-NFκB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction 96%
- Complement 3a Receptor 1 on Macrophages and Kupffer cells is not required for the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease 96%
- Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis 96%
Similar papers in this journal
- The Diabetes Gene Tcf7l2 Organizes Gene Expression in the Liver and Regulates Amino Acid Metabolism 95%
- Leukocyte-type 12/15-lipoxygenase is essential for timely inflammation-resolution and effective tissue regeneration following skeletal muscle injury 94%
- Mesenchymal-specific Alms1 knockout in mice recapitulates key metabolic features of Alström Syndrome 94%
Similar papers in this journal
- Rapid in vivo multiplexed editing (RIME) of the adult mouse liver 95%
- Vascular damage and excessive proliferation compromise liver function after extended hepatectomy in mice 95%
- Suppression of Fatty Acid Oxidation by Thioesterase Superfamily Member 2 in Skeletal Muscle Promotes Hepatic Steatosis and Insulin Resistance 94%
Similar papers in this journal
- Scar-associated endothelial-stellate cellular crosstalk drives fibrosis resolution in MASH 95%
- Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism 94%
- Atrial natriuretic peptide orchestrates a coordinated physiological response to fuel non shivering thermogenesis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.