ArticleProceedings of the National Academy of Sciences of the United States of America2002
C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 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
100 citing papers in PubMed, 260 citations in OpenAlex.
- Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.PloS one · 2012Trial
- Productive Mayaro Virus Infection Requires Host Fatty Acid Synthase for nsP1 S-palmitoylation.bioRxiv : the preprint server for biology · 2026Article
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer.Neoplasia (New York, N.Y.) · 2025Article
- Mechanisms of Abnormal Lipid Metabolism in the Pathogenesis of Disease.International journal of molecular sciences · 2024Review
- Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology.Molecular oncology · 2024Article
- TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.The Journal of clinical investigation · 2024Article
- Excess glucose or fat differentially affects metabolism and appetite-related gene expression during zebrafish embryogenesis.iScience · 2023Article
- Mitochondrial morphology controls fatty acid utilization by changing CPT1 sensitivity to malonyl-CoA.The EMBO journal · 2023Article
- Physiological and pathological roles of lipogenesis.Nature metabolism · 2023Review
- Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer.Biomolecules · 2022Review
- Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment.Genes, brain, and behavior · 2022Article
- Lipogenesis inhibitors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2022Review
- Fatty acid-binding proteins and fatty acid synthase influence glial reactivity and promote the formation of Müller glia-derived progenitor cells in the chick retina.Development (Cambridge, England) · 2022Article
- Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma.Acta pharmaceutica Sinica. B · 2022Review
- Progress of potential drugs targeted in lipid metabolism research.Frontiers in pharmacology · 2022Review
- A Scalable Human Intestinal Planar Culture Offers Opportunities for High-throughput Drug Testing.Cellular and molecular gastroenterology and hepatology · 2022Article
- A Planar Culture Model of Human Absorptive Enterocytes Reveals Metformin Increases Fatty Acid Oxidation and Export.Cellular and molecular gastroenterology and hepatology · 2022Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
C75, a known inhibitor of fatty acid synthase is postulated to cause significant weight loss through decreased hypothalamic neuropeptide Y (NPY) production. Peripherally, C75, an alpha-methylene-gamma-butyrolactone, reduces adipose tissue and fatty liver, despite high levels of malonyl-CoA. To investigate this paradox, we studied the effect of C75 on fatty acid oxidation and energy production in diet-induced obese (DIO) mice and cellular models. Whole-animal calorimetry showed that C75-treated DIO mice had a 50% greater weight loss, and a 32.9% increased production of energy because of fatty acid oxidation, compared with paired-fed controls. Etomoxir, an inhibitor of carnitine O-palmitoyltransferase-1 (CPT-1), reversed the increased energy expenditure in DIO mice by inhibiting fatty acid oxidation. C75 treatment of rodent adipocytes and hepatocytes and human breast cancer cells increased fatty acid oxidation and ATP levels by increasing CPT-1 activity, even in the presence of elevated concentrations of malonyl-CoA. Studies in human cancer cells showed that C75 competed with malonyl-CoA, as measured by CPT-1 activity assays. Thus, C75 acts both centrally to reduce food intake and peripherally to increase fatty acid oxidation, leading to rapid and profound weight loss, loss of adipose mass, and resolution of fatty liver. The pharmacological stimulation of CPT-1 activity is a novel finding. The dual action of the C75 class of compounds as fatty acid synthase inhibitors and CPT-1 agonists has therapeutic implications in the treatment of obesity and type II diabetes.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.