Objective: The link between a reduced capacity for skeletal muscle mitochondrial fatty acid oxidation (FAO) and lipotoxicity in human insulin resistance has been the subject of intense debate. The objective of this study was to investigate whether reduced FAO is associated with elevated acyl CoA, ceramide, and diacylglycerol (DAG) in severely obese insulin resistant subjects.
Methods: Muscle biopsies were conducted in lean (L, 22.6 ± 0.5 kg/m(2) , n = 8), Class I (CI, 32.1 ± 0.4 kg/m(2) , n = 7) and Class II&III obese (CII&III, 45.6 ± 1.1 kg/m(2) , n = 15) women for acyl CoA, sphingolipid and DAG profiling. Intramyocellular triglyceride (IMTG) content was determined by histology. FAO was assessed by incubating muscle homogenates with [1-C]palmitate and measuring CO2 production. Cardiolipin content was quantified as an index of mitochondrial content. Lipid metabolism proteins, DGAT1, PLIN5, and PNPLA2 were quantified in biopsy samples by western blot.
Results: CII&III were more insulin resistant (HOMA-IR: 4.5 ± 0.5 vs. 1.1 ± 0.1, P < 0.001), and had lower FAO (∼58%, P = 0.007) and cardiolipin content (∼31%, P = 0.013) compared to L. IMTG was elevated in CI (P = 0.04) and CII&III (P = 0.04) compared to L. Sphingolipid content was higher in CII&III compared to L (13.6 ± 1.1 vs. 10.3 ± 0.5 pmol/mg, P = 0.031) whereas DAG content was not different among groups. DGAT1 was elevated in CII&III, and PLIN5 was elevated in CI compared to L.
Conclusions: Severe obesity is associated with reduced muscle oxidative capacity and occurs concomitantly with elevated IMTG, ceramide and insulin resistance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136513 | PMC |
| http://dx.doi.org/10.1002/oby.20381 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1.
J Clin Invest
January 2025
Center for Inherited Myology Research, Virginia Commonwealth University, Richmond, United States of America.
Background: Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness.
View Article and Find Full Text PDFA new model of experimental diabetic cardiomyopathy using combination of multiple doses of anomer-equilibrated streptozotocin and high fat diet: sex matters.
Diabetes
January 2025
William Harvey Research Institute, Barts Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Diabetes mellitus (DM) leads to a more rapid development of DM cardiomyopathy (dbCM) and progression to heart failure in women than men. Combination of high-fat diet (HFD) and freshly-injected streptozotocin (STZ) has been widely used for DM induction, however emerging data shows that anomer-equilibrated STZ produces an early onset and robust DM model. We designed a novel protocol utilising a combination of multiple doses of anomer-equilibrated STZ injections and HFD to develop a stable murine DM model featuring dbCM analogous to humans.
View Article and Find Full Text PDFComparison of perioperative analgesic effectiveness of ultrasound-guided erector spinae plane block and transversus abdominis plane block in patients undergoing laparoscopic nephrectomy.
Agri
January 2025
Department of Anesthesiology and Reanimation, Bursa Uludağ University Faculty of Medicine, Bursa, Türkiye.
Objectives: In this study, we aimed to compare the efficacy of two regional anesthesia methods, transversus abdominis plane (TAP) block and erector spinae plane (ESP) block, for intraoperative and postoperative pain relief in patients undergoing laparoscopic nephrectomy.
Methods: Fifty patients aged 18-80 years with American Society of Anesthesiologists (ASA) classification I-II scheduled for elective laparoscopic nephrectomy were included after ethical approval and informed consent. Patients were randomly assigned to either Group TAP (receiving TAP block) or Group ESP (receiving ESP block).
Comparison of postoperative analgesic efficacy between erector spinae plane block and rhomboid intercostal block in breast-conserving surgery and sentinel lymph node biopsy: A randomized non-inferiority clinical trial.
Agri
January 2025
Department of Anesthesiology and Reanimation, İstanbul Medipol University Faculty of Medicine, İstanbul, Türkiye.
Objectives: Breast-conserving surgery is a common breast operation type in the world. Patients may feel severe postoperative pain after the surgery. Several regional anesthesia methods are used for postoperative pain control as a part of multimodal analgesia management after breast surgery.
View Article and Find Full Text PDFHistogram of Apparent Diffusion Coefficient to Evaluate the Activity of Thyroid-Associated Ophthalmopathy.
Immun Inflamm Dis
January 2025
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Objective: This study aimed to evaluate the activity of extraocular muscles (EOMs) in patients with thyroid-associated ophthalmopathy (TAO) using turbo spin echo imaging. By analyzing tissue heterogeneity, apparent diffusion coefficient (ADC) histogram analysis offers enhanced insights into edema within the EOMs.
Methods: Eighty-eight patients with TAO were retrospectively evaluated and allocated into active (n = 24, clinical activity score [CAS] ≥ 3) and inactive (n = 64, CAS < 3) groups.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!