ArticleAmerican journal of physiology. Endocrinology and metabolism2015
MyD88 regulates physical inactivity-induced skeletal muscle inflammation, ceramide biosynthesis signaling, and glucose intolerance.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The trial behind it
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Neuromuscular electrical stimulation and protein during bed rest increases CD11bApplied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2020Trial
- Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks of simulated sedentary behaviour and recovery in healthy older adults.The Journal of physiology · 2018Trial
- Review
- Kynurenine pathway dysregulation via loss of QPRT drives declines in activity and altered metabolism in mice.GeroScience · 2026Article
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- HDAC9 in Insulin Resistance: An Update on Epigenetic Mechanisms, Inflammatory Crosstalk, and Therapeutic Potential.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Ceramide in Coronary Artery Disease: Troublesome or Helpful Future Tools in the Assessment of Risk Prediction and Therapy Effectiveness?Metabolites · 2025Review
- The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration.Nature cardiovascular research · 2024Article
- Positive Effects of Physical Activity on Insulin Signaling.Current issues in molecular biology · 2024Review
- Exercise Restores Hypothalamic Health in Obesity by Reshaping the Inflammatory Network.Antioxidants (Basel, Switzerland) · 2023Review
- A Transcriptomic Regulatory Network among miRNAs, lncRNAs, circRNAs, and mRNAs Associated with L-leucine-induced Proliferation of Equine Satellite Cells.Animals : an open access journal from MDPI · 2023Article
- Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity.Life (Basel, Switzerland) · 2022Article
- Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Pathophysiology and Treatment Strategies of Acute Myopathy and Muscle Wasting after Sepsis.Journal of clinical medicine · 2021Review
- Preclinical rodent models of physical inactivity-induced muscle insulin resistance: challenges and solutions.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Review
- Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension.International journal of molecular sciences · 2021Article
- Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence.Journal of diabetes research · 2021Review
- Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity-Induced Adiposity and Insulin Resistance.Obesity (Silver Spring, Md.) · 2020Article
- Pharmacological inhibition of TLR4 ameliorates muscle and liver ceramide content after disuse in previously physically active mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Changes in Membrane Ceramide Pools in Rat Soleus Muscle in Response to Short-Term Disuse.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Physical inactivity in older adults is a risk factor for developing glucose intolerance and impaired skeletal muscle function. Elevated inflammation and ceramide biosynthesis have been implicated in metabolic disruption and are linked to Toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) signaling. We hypothesize that a physical inactivity stimulus, capable of inducing glucose intolerance, would increase skeletal muscle inflammation and ceramide biosynthesis signaling and that this response would be regulated by the TLR/MyD88 pathway. Therefore, we subjected wild-type (WT) and MyD88(-/-) mice to hindlimb unloading (HU) for 14 days or an ambulatory control period. We observed impaired glucose uptake, muscle insulin signaling (p-Akt), and increased markers of NF-κB signaling (p-IκBα), inflammation (p-JNK, IL-6), TLR4, and the rate-limiting enzyme of ceramide biosynthesis, SPT2, with HU WT (P < 0.05), but not in HU MyD88(-/-) mice. Concurrently, we found that 5 days of bed rest in older adults resulted in whole body glucose dysregulation, impaired skeletal muscle insulin signaling, and upregulation of muscle IL-6 and SPT2 (P < 0.05). Post-bed rest TLR4 abundance was tightly correlated with impaired postprandial insulin and glucose levels. In conclusion, MyD88 signaling is necessary for the increased inflammation, ceramide biosynthesis signaling, and compromised metabolic function that accompanies physical inactivity.
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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.