ArticleJournal of cachexia, sarcopenia and muscle2026
Elevated Kallistatin Induces Myosteatosis and Exercise Intolerance by Antagonizing AdipoR1-Mediated AMPK Signalling.
Article in Journal of cachexia, sarcopenia and muscle, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
backgroundPathological intramuscular lipid deposition (myosteatosis) and exercise intolerance are hallmarks of metabolic disorders, including diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD), yet their underlying mechanisms remain unclear. Our previous work has confirmed that hypertriglyceridemia-driven kallistatin (KAL) elevation is present in the peripheral blood of patients with MASLD and diabetes and is a causative factor in hepatic steatosis and MASH pathogenesis. Here, we aim to evaluate this elevated KAL on myosteatosis and exercise function.
methodsWe first established rat models of myosteatosis via a high-fat diet or high-fructose water intake and measured serum KAL levels by immunoblotting. KAL transgenic (KAL-TG) mice were generated and subjected to longitudinal analyses, including Oil Red O staining for lipid deposition, exercise tolerance tests, indirect calorimetry for energy expenditure, mitochondrial DNA copy number quantification, ATP measurement, immunoblotting and quantitative PCR. For mechanistic analyses, mouse C2C12 myotubes were treated with recombinant KAL or KAL adenovirus, with or without co-treatment with AICAR, AdipoRon or AdipoR1 siRNA. Additionally, we evaluated the potential ameliorative effects of KAL knockout and target agonists on myosteatosis.
resultsSerum KAL levels were significantly elevated in rat models of myosteatosis. Conversely, genetic ablation of KAL ameliorated diet-induced muscle lipid deposition. KAL-TG mice developed myosteatosis (muscle TG [μmol/g]: WT: 54.26 ± 14.56 [95% CI: 38.99-69.54]; KAL-TG: 85.13 ± 11.53 [95% CI: 73.03-97.24], p < 0.01) and exhibited exercise intolerance (p < 0.05 for all) from 6 months of age. Mechanistically, KAL bound to sarcolemmal adiponectin receptor 1 (AdipoR1), suppressing AMPK activity. This led to reduced phosphorylation of acetyl-CoA carboxylase (ACC) (p < 0.05), enhancing lipogenesis and downregulated the PGC-1α/NRF1 axis (p < 0.05), impairing mitochondrial biogenesis and reducing ATP production (p < 0.05). Pharmacological activation of AdipoR1 (AdipoRon) and fenofibrate attenuated myosteatosis and restored exercise capacity in KAL-TG mice (p < 0.05).
conclusionsAbnormal elevation of KAL drives metabolic myopathy and exercise intolerance by antagonizing the AdipoR1-AMPK axis. Our findings offer dual strategies: repurposing AdipoR1 agonists (e.g., AdipoRon) or reducing circulating KAL (e.g., via genetic ablation or triglyceride-lowering agents such as fenofibrate), both applicable to diabetes/MASLD-related metabolic myopathy.
Indexed as
Identifiers
What OpenQuestion holds
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.