ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Elevated levels of TWEAK in skeletal muscle promote visceral obesity, insulin resistance, and metabolic dysfunction.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting TWEAK to enhance mitochondrial biogenesis and attenuate age-related muscle mass loss.Scientific reports · 2026Article
- Fiber-type vulnerability and proteostasis reprogramming in skeletal muscle during pancreatic cancer cachexia.JCI insight · 2026Article
- Inhibition of TWEAK/Fn14 Ameliorates Sarcopenic Obesity by Restoring Mitochondrial Biogenesis via the AMPK/SIRT1/PGC-1α Axis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- The canonical ER stress IRE1α/XBP1 pathway mediates skeletal muscle wasting during pancreatic cancer cachexia.EMBO molecular medicine · 2025Article
- Mifepristone alone and in combination with scAAV9-SMN1 gene therapy improves disease phenotypes in SmnScientific reports · 2025Article
- Fiber-type vulnerability and proteostasis reprogramming in skeletal muscle during pancreatic cancer cachexia.bioRxiv : the preprint server for biology · 2025Article
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- Observational
- Exercise, disease state and sex influence the beneficial effects of Fn14-depletion on survival and muscle pathology in the SOD1Skeletal muscle · 2024Article
- Targeted ablation of Fn14 receptor improves exercise capacity and inhibits neurogenic muscle atrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.Skeletal muscle · 2022Article
- Circulating sTweak is associated with visceral adiposity and severity in patients with obstructive sleep apnea syndrome.Scientific reports · 2021Article
- Control strategies in systemic metabolism.Nature metabolism · 2019Review
- The Toll-Like Receptor/MyD88/XBP1 Signaling Axis Mediates Skeletal Muscle Wasting during Cancer Cachexia.Molecular and cellular biology · 2019Article
- TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?Clinical science (London, England : 1979) · 2019Review
- PGC1α: Friend or Foe in Cancer?Genes · 2018Review
- Role of Omentin, Vaspin, Cardiotrophin-1, TWEAK and NOV/CCN3 in Obesity and Diabetes Development.International journal of molecular sciences · 2017Review
- TWEAK blockade decreases atherosclerotic lesion size and progression through suppression of STAT1 signaling in diabetic mice.Scientific reports · 2017Article
- Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Skeletal muscle is responsible for the majority of glucose disposal in body. Impairment in skeletal muscle glucose handling capacity leads to the state of insulin resistance. The TNF-like weak inducer of apoptosis (TWEAK) cytokine has now emerged as a major regulator of skeletal muscle mass and function. However, the role of TWEAK in skeletal muscle metabolic function remains less understood. Here, we demonstrate that with progressive age, skeletal muscle-specific TWEAK-transgenic (TWEAK-Tg) mice gain increased body weight (∼16%) and fat mass (∼64%) and show glucose intolerance and insulin insensitivity. TWEAK-Tg mice also exhibit adipocyte hypertrophy in the epididymal fat. Oxygen uptake, voluntary physical activity, and exercise capacity were significantly reduced in TWEAK-Tg mice compared with controls. Overexpression of TWEAK inhibited (∼31%) 5' AMP-activated protein kinase (AMPK) and reduced (∼31%) the levels of glucose transporter type 4 (GLUT4) without affecting the Akt pathway. TWEAK also inhibited insulin-stimulated glucose uptake (∼32%) and repressed the levels of GLUT4 (∼50%) in cultured myotubes from C57BL6 mice. TWEAK represses the levels of Krüppel-like factor 15; myocyte enhancer factor 2, and peroxisome proliferator-activated receptor-γ coactivator-1α, which are required for the activation of the GLUT4 locus. Collectively our study demonstrates that elevated levels of TWEAK in skeletal muscle cause metabolic abnormalities. Inhibition of TWEAK could be a potential approach to prevent weight gain and type 2 diabetes.
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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.