ArticleMolecular metabolism2016
mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Integrative transcriptomics and machine learning reveal key regulatory genes for meat quality traits in pigs.BMC genomics · 2026Article
- PLIN3: a multifaceted regulator of lipid droplet dynamics and disease pathogenesis.Medical oncology (Northwood, London, England) · 2025Review
- Perilipins: key targets for regulating lipid metabolism and alleviating abnormal lipid metabolism through exercise.Diabetology & metabolic syndrome · 2025Review
- The Heart Has Intrinsic Ketogenic Capacity that Mediates NADCirculation research · 2025Article
- Loss of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Regulation and Limits Exercise Capacity.International journal of molecular sciences · 2025Article
- Article
- Genetic Deletion of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Homeostasis and Impairs Exercise Tolerance.bioRxiv : the preprint server for biology · 2024Article
- Unraveling the role of lipid droplets and perilipin 2 in bovine luteal cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Differential intracellular management of fatty acids impacts on metabolic stress-stimulated glucose uptake in cardiomyocytes.Scientific reports · 2023Article
- Functional Nutrients to Ameliorate Neurogenic Muscle Atrophy.Metabolites · 2022Review
- Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells.Nature communications · 2022Article
- Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2022Article
- Energy transfer between the mitochondrial network and lipid droplets in insulin resistant skeletal muscle.Current opinion in physiology · 2021Article
- Article
- Review
- Plasma levels of trimethylamine-N-oxide can be increased with 'healthy' and 'unhealthy' diets and do not correlate with the extent of atherosclerosis but with plaque instability.Cardiovascular research · 2021Article
- Article
- Lactate production is a prioritized feature of adipocyte metabolism.The Journal of biological chemistry · 2020Article
- mTORC2 affects the maintenance of the muscle stem cell pool.Skeletal muscle · 2019Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe have recently shown that acute inhibition of both mTOR complexes (mTORC1 and mTORC2) increases whole-body lipid utilization, while mTORC1 inhibition had no effect. Therefore, we tested the hypothesis that mTORC2 regulates lipid metabolism in skeletal muscle.
methodsBody composition, substrate utilization and muscle lipid storage were measured in mice lacking mTORC2 activity in skeletal muscle (specific knockout of RICTOR (Ric mKO)). We further examined the RICTOR/mTORC2-controlled muscle metabolome and proteome; and performed follow-up studies in other genetic mouse models and in cell culture.
resultsRic mKO mice exhibited a greater reliance on fat as an energy substrate, a re-partitioning of lean to fat mass and an increase in intramyocellular triglyceride (IMTG) content, along with increases in several lipid metabolites in muscle. Unbiased proteomics revealed an increase in the expression of the lipid droplet binding protein Perilipin 3 (PLIN3) in muscle from Ric mKO mice. This was associated with increased AMPK activity in Ric mKO muscle. Reducing AMPK kinase activity decreased muscle PLIN3 expression and IMTG content. AMPK agonism, in turn, increased PLIN3 expression in a FoxO1 dependent manner. PLIN3 overexpression was sufficient to increase triglyceride content in muscle cells.
conclusionsWe identified a novel link between mTORC2 and PLIN3, which regulates lipid storage in muscle. While mTORC2 is a negative regulator, we further identified AMPK as a positive regulator of PLIN3, which impacts whole-body substrate utilization and nutrient partitioning.
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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.