ArticleThe Journal of biological chemistry2015
Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus.Frontiers in endocrinology · 2022Trial
- 4-Phenylbutyric acid activates an NF-κB-Egr-1 axis to control myoblast proliferation and ECM gene expression.iScience · 2026Article
- The Rising Burden of Osteosarcopenia in Older Adults: A Narrative Review of Pathophysiology, Diagnostic Challenges, and Therapeutic Perspectives.Health science reports · 2026Article
- CXCL5 neutralization mitigates cancer cachexia by disrupting CAF-cancer cell crosstalk.Journal of biomedical science · 2025Article
- Combating muscle atrophy: emerging therapeutic targets that are fiber-type-specific.The FEBS journal · 2025Review
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- DNA repair and disease: insights from the human DNA glycosylase NEIL family.Experimental & molecular medicine · 2025Review
- Dietary polyphenols and sarcopenia: epigenetic mechanisms and geroscience perspectives for muscle health in aging.Frontiers in aging · 2025Review
- Epigenetics of Skeletal Muscle Atrophy.International journal of molecular sciences · 2024Review
- Ursolic Acid Induces Beneficial Changes in Skeletal Muscle mRNA Expression and Increases Exercise Participation and Performance in Dogs with Age-Related Muscle Atrophy.Animals : an open access journal from MDPI · 2024Article
- Impact of osteopenia and osteosarcopenia on the outcomes after surgery of hepatobiliary-pancreatic cancers.Frontiers in oncology · 2024Article
- Muscle-bone crosstalk via endocrine signals and potential targets for osteosarcopenia-related fracture.Journal of orthopaedic translation · 2023Review
- Osteopenia Is Associated with Shorter Survival in Patients with Intrahepatic Cholangiocarcinoma.Current oncology (Toronto, Ont.) · 2023Article
- Article
- Preoperative Osteopenia Is Associated with Significantly Shorter Survival in Patients with Perihilar Cholangiocarcinoma.Cancers · 2022Article
- TNF-α Induced Myotube Atrophy in C2C12 Cell Line Uncovers Putative Inflammatory-Related lncRNAs Mediating Muscle Wasting.International journal of molecular sciences · 2022Article
- Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging.International journal of molecular sciences · 2021Review
- The Role of Osteokines in Sarcopenia: Therapeutic Directions and Application Prospects.Frontiers in cell and developmental biology · 2021Review
- How to Overcome Anabolic Resistance in Dialysis-Treated Patients?Frontiers in nutrition · 2021Review
- Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
NF-κB is best known for its pro-inflammatory and anti-apoptotic actions, but in skeletal muscle, NF-κB activation is important for atrophy upon denervation or cancer. Here, we show that also upon fasting, NF-κB becomes activated in muscle and is critical for the subsequent atrophy. Following food deprivation, the expression and acetylation of the p65 of NF-κB on lysine 310 increase markedly in muscles. NF-κB inhibition in mouse muscles by overexpression of the IκBα superrepressor (IκBα-SR) or of p65 mutated at Lys-310 prevented atrophy. Knockdown of GCN5 with shRNA or a dominant-negative GCN5 or overexpression of SIRT1 decreased p65K310 acetylation and muscle wasting upon starvation. In addition to reducing atrogene expression, surprisingly inhibiting NF-κB with IκBα-SR or by GCN5 knockdown in these muscles also enhanced AKT and mechanistic target of rapamycin (mTOR) activities, which also contributed to the reduction in atrophy. These new roles of NF-κB and GCN5 in regulating muscle proteolysis and AKT/mTOR signaling suggest novel approaches to combat muscle wasting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.