ArticleProceedings of the National Academy of Sciences of the United States of America2015
Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A.The American journal of clinical nutrition · 2020Pooled it
- Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.Metabolism: clinical and experimental · 2021Trial
- TAK1 Regulates Skeletal Muscle Mass, Hypertrophic Signaling, and Metabolic Homeostasis in Male and Female Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- TAK1 regulates skeletal muscle mass, hypertrophic signaling, and metabolic homeostasis in male and female mice.bioRxiv : the preprint server for biology · 2026Article
- From Adipose Dysfunction to Multi-Organ Steatosis: Defining the Metabolic Steatotic Axis.Current issues in molecular biology · 2026Review
- Sirt1 coordinates the mitochondrial UPR and myocellular proteostasis to preserve muscle integrity during muscle atrophy in zebrafish.Frontiers in cell and developmental biology · 2026Article
- Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline.Diseases (Basel, Switzerland) · 2025Review
- Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis.Cell metabolism · 2025Article
- L-Arginine Supplementation Improves Endurance Under Chronic Fatigue: Inducing In Vivo Paradigms with In Vitro Support.Nutrients · 2025Article
- Hepatic Inactivation of Carnitine Palmitoyltransferase 1a Lowers ApoB-Containing Lipoproteins in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Apocynin Mitigates Diabetic Muscle Atrophy by Lowering Muscle Triglycerides and Oxidative Stress.International journal of molecular sciences · 2025Article
- Targeting intramyocellular lipids to improve aging muscle function.Lipids in health and disease · 2025Review
- Skeletal muscle disorders as risk factors for type 2 diabetes.Molecular and cellular endocrinology · 2025Review
- Tissue specific roles of fatty acid oxidation.Advances in biological regulation · 2025Review
- Carnitine palmitoyltransferase 1 facilitates fatty acid oxidation in a non-cell-autonomous manner.Cell reports · 2024Article
- Age-related TFEB downregulation in proximal tubules causes systemic metabolic disorders and occasional apolipoprotein A4-related amyloidosis.JCI insight · 2024Article
- Exercise Therapy Rescues Skeletal Muscle Dysfunction and Exercise Intolerance in Cardiometabolic HFpEF.JACC. Basic to translational science · 2024Article
- Reducing the mitochondrial oxidative burden alleviates lipid-induced muscle insulin resistance in humans.Science advances · 2024Article
- Overexpression of CPT1A disrupts the maintenance and regenerative function of muscle stem cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The correlations between intramyocellular lipid (IMCL), decreased fatty acid oxidation (FAO), and insulin resistance have led to the hypothesis that impaired FAO causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling. Using a skeletal muscle-specific carnitine palmitoyltransferase-1 KO model, we show that prolonged and severe mitochondrial FAO inhibition results in increased carbohydrate utilization, along with reduced physical activity; increased circulating nonesterified fatty acids; and increased IMCLs, diacylglycerols, and ceramides. Perhaps more importantly, inhibition of mitochondrial FAO also initiates a local, adaptive response in muscle that invokes mitochondrial biogenesis, compensatory peroxisomal fat oxidation, and amino acid catabolism. Loss of its major fuel source (lipid) induces an energy deprivation response in muscle coordinated by signaling through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) to maintain energy supply for locomotion and survival. At the whole-body level, these adaptations result in resistance to obesity.
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.