ArticleCell cycle (Georgetown, Tex.)2015
Leptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation, cytokine production and increased cell proliferation.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
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- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
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- The Oncogenic Burden of Obesity: Mechanistic Links Between Adiposity and Gastrointestinal Cancers-A Comprehensive Narrative Review.Biomedicines · 2025Review
- Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation.Frontiers in immunology · 2025Review
- Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- Terminalia bellirica and Andrographis paniculata dietary supplementation in mitigating heat stress-induced behavioral, metabolic and genetic alterations in broiler chickens.BMC veterinary research · 2024Article
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- Inhalation exposure-induced toxicity and disease mediated via mTOR dysregulation.Experimental biology and medicine (Maywood, N.J.) · 2024Review
- [Associations of circulating leptin levels with colorectal adenoma and colorectal cancer: a case-control and Mendelian randomization study].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Leptin: A Heavyweight Player in Obesity-Related Cancers.Biomolecules · 2023Review
- Obesity, the Adipose Organ and Cancer in Humans: Association or Causation?Biomedicines · 2023Review
- Creeping fat formation and interaction with intestinal disease in Crohn's disease.United European gastroenterology journal · 2022Review
- Impact of Obesity on the Course of Management of Inflammatory Bowel Disease-A Review.Nutrients · 2022Review
- Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage.Biomedicines · 2022Review
- Influence of dietary vitamin E and selenium supplementation on broilers subjected to heat stress, Part II: oxidative stress, immune response, gut integrity, and intestinal microbiota.Poultry science · 2022Article
- Targeting mTOR in the Context of Diet and Whole-body Metabolism.Endocrinology · 2022Review
- Leptin Silencing Attenuates Lipid Accumulation through Sterol Regulatory Element-Binding Protein 1 Inhibition in Nasopharyngeal Carcinoma.International journal of molecular sciences · 2022Article
- Comparison of transcriptome between high- and low-marbling fineness in longissimus thoracis muscle of Korean cattle.Animal bioscience · 2022Article
- A review on the role of fatty acids in colorectal cancer progression.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma.
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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.