ArticleLipids2010
mTORC1 inhibition via rapamycin promotes triacylglycerol lipolysis and release of free fatty acids in 3T3-L1 adipocytes.
Article in Lipids, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Hepatic loss of AATF attenuates MASH by suppressing AKT-mTORC1 signaling and reprogramming lipid metabolism.Molecular medicine (Cambridge, Mass.) · 2026Article
- PANoptosis in diabetes: immunometabolic insights and treatments.Apoptosis : an international journal on programmed cell death · 2026Review
- Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue.Cell death & disease · 2025Article
- Dietary Restriction and Lipid Metabolism: Unveiling Pathways to Extended Healthspan.Nutrients · 2024Review
- A sustainable nutritional solution for fattening pigs based on 25-hydroxycholecalciferol and triterpenoids added to a low Ca diet containing phytase improves growth performance via the activation of muscle protein synthesis without compromising bone mineralization.Translational animal science · 2024Article
- Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review.Frontiers in pharmacology · 2023Review
- Article
- Article
- G-Protein Coupled Receptor Signaling and Mammalian Target of Rapamycin Complex 1 Regulation.Molecular pharmacology · 2022Review
- Lipid metabolism, inflammation, and foam cell formation in health and metabolic disorders: targeting mTORC1.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Lipid metabolism and lipid signals in aging and longevity.Developmental cell · 2021Review
- Wnt/β-catenin signaling regulates adipose tissue lipogenesis and adipocyte-specific loss is rigorously defended by neighboring stromal-vascular cells.Molecular metabolism · 2020Article
- The Synergistic Effect of an ATP-Competitive Inhibitor of mTOR and Metformin on Pancreatic Tumor Growth.Current developments in nutrition · 2020Article
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- mTORC1 restrains adipocyte lipolysis to prevent systemic hyperlipidemia.Molecular metabolism · 2020Article
- Lysophosphatidic acid reverses Temsirolimus-induced changes in lipid droplets and mitochondrial networks in renal cancer cells.PloS one · 2020Article
- A novel rapamycin analog is highly selective for mTORC1 in vivo.Nature communications · 2019Article
- Review
- Mammalian target of rapamycin complex 1 and FoxO1 in the transcriptional control of lipolysis and de novo lipogenesis.Current opinion in endocrinology, diabetes, and obesity · 2017Article
- Rheb Inhibits Beiging of White Adipose Tissue via PDE4D5-Dependent Downregulation of the cAMP-PKA Signaling Pathway.Diabetes · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Signaling by mTOR complex 1 (mTORC1) promotes anabolic cellular processes in response to growth factors, nutrients, and hormonal cues. Numerous clinical trials employing the mTORC1 inhibitor rapamycin (aka sirolimus) to immuno-suppress patients following organ transplantation have documented the development of hypertriglyceridemia and elevated serum free fatty acids (FFA). We therefore investigated the cellular role of mTORC1 in control of triacylglycerol (TAG) metabolism using cultured murine 3T3-L1 adipocytes. We found that treatment of adipocytes with rapamycin reduced insulin-stimulated TAG storage ~50%. To determine whether rapamycin reduces TAG storage by upregulating lipolytic rate, we treated adipocytes in the absence and presence of rapamycin and isoproterenol, a β2-adrenergic agonist that activates the cAMP/protein kinase A (PKA) pathway to promote lipolysis. We found that rapamycin augmented isoproterenol-induced lipolysis without altering cAMP levels. Rapamycin enhanced the isoproterenol-stimulated phosphorylation of hormone sensitive lipase (HSL) on Ser-563 (a PKA site), but had no effect on the phosphorylation of HSL S565 (an AMPK site). Additionally, rapamycin did not affect the isoproterenol-mediated phosphorylation of perilipin, a protein that coats the lipid droplet to initiate lipolysis upon phosphorylation by PKA. These data demonstrate that inhibition of mTORC1 signaling synergizes with the β-adrenergic-cAMP/PKA pathway to augment phosphorylation of HSL to promote hormone-induced lipolysis. Moreover, they reveal a novel metabolic function for mTORC1; mTORC1 signaling suppresses lipolysis, thus augmenting TAG storage.
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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.