ArticleAmerican journal of physiology. Endocrinology and metabolism2019
Excess membrane cholesterol is an early contributing reversible aspect of skeletal muscle insulin resistance in C57BL/6NJ mice fed a Western-style high-fat diet.
Article in American journal of physiology. Endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed, 20 citations in OpenAlex.
- LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.The Journal of clinical investigation · 2024Trial
- Integrin-linked kinase promotes hepatic fat accumulation via F-actin stabilization-dependent CD36 plasma membrane localization.iScience · 2026Article
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- 25-Hydroxycholesterol as a negative regulator of diaphragm muscle contractions via estrogen receptor and CaHistochemistry and cell biology · 2025Article
- Association of remnant cholesterol with sarcopenia in Korean adults: a nationwide population-based study using data from the KNHANES.Frontiers in endocrinology · 2024Article
- Inflammation and Fatty Infiltration Correlates with Rotator Cuff Muscle Atrophy in Hypercholesterolemic Yucatan Microswine.Journal of orthopaedics and sports medicine · 2024Article
- Plant-derived cell-penetrating microprotein α-astratide aM1 targets Akt signaling and alleviates insulin resistance.Cellular and molecular life sciences : CMLS · 2023Article
- Insulin signalling and GLUT4 trafficking in insulin resistance.Biochemical Society transactions · 2023Review
- Cholesterol: An Important Determinant of Muscle Atrophy in Astronauts.Journal of biotechnology and biomedicine · 2023Article
- Exercise sustains the hallmarks of health.Journal of sport and health science · 2023Review
- Gene deletion of γ-actin impairs insulin-stimulated skeletal muscle glucose uptake in growing mice but not in mature adult mice.Physiological reports · 2022Article
- Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats.Facets (Ottawa) · 2022Article
- Sphingolipids and Cholesterol.Advances in experimental medicine and biology · 2022Article
- d-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats.Molecules (Basel, Switzerland) · 2021Article
- Reduced membrane cholesterol content in skeletal muscle is not essential for greater insulin-stimulated glucose uptake after acute exercise by rats.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Skeletal muscle insulin resistance manifests shortly after high-fat feeding, yet mechanisms are not known. Here we set out to determine whether excess skeletal muscle membrane cholesterol and cytoskeletal derangement known to compromise glucose transporter (GLUT)4 regulation occurs early after high-fat feeding. We fed 6-wk-old male C57BL/6NJ mice either a low-fat (LF, 10% kcal) or a high-fat (HF, 45% kcal) diet for 1 wk. This HF feeding challenge was associated with an increase, albeit slight, in body mass, glucose intolerance, and hyperinsulinemia. Liver analyses did not reveal signs of hepatic insulin resistance; however, skeletal muscle immunoblots of triad-enriched regions containing transverse tubule membrane showed a marked loss of stimulated GLUT4 recruitment. An increase in cholesterol was also found in these fractions from HF-fed mice. These derangements were associated with a marked loss of cortical filamentous actin (F-actin) that is essential for GLUT4 regulation and known to be compromised by increases in membrane cholesterol. Both the withdrawal of the HF diet and two subcutaneous injections of the cholesterol-lowering agent methyl-β-cyclodextrin at 3 and 6 days during the 1-wk HF feeding intervention completely mitigated cholesterol accumulation, cortical F-actin loss, and GLUT4 dysregulation. Moreover, these beneficial membrane/cytoskeletal changes occurred concomitant with a full restoration of metabolic responses. These results identify skeletal muscle membrane cholesterol accumulation as an early, reversible, feature of insulin resistance and suggest cortical F-actin loss as an early derangement of skeletal muscle insulin resistance.
Indexed as
Identifiers
What Socratic 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 Socratic graph.