ArticleProceedings of the National Academy of Sciences of the United States of America2011
Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?Arthritis research & therapy · 2013Trial
- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic ceramide metabolism in obesity and dysregulation of glucose homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- Cellular mechanisms of brain lipid metabolism in health and disease.Nature cell biology · 2026Review
- Malonyl-CoA Decarboxylase: A Spotlight on Brain Aspects.Brain sciences · 2026Review
- CPT1C deficiency in SF1 neurons impairs early metabolic adaptation to dietary fats, leading to obesity.Molecular metabolism · 2025Article
- Shared Pathophysiological Mechanisms and Genetic Factors in Early Menarche and Polycystic Ovary Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids.Cell reports. Medicine · 2024Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.Nature communications · 2023Article
- Central Regulation of Brown Fat Thermogenesis in Response to Saturated or Unsaturated Long-Chain Fatty Acids.International journal of molecular sciences · 2023Article
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Transcriptome Comparison Reveals the Difference in Liver Fat Metabolism between Different Sheep Breeds.Animals : an open access journal from MDPI · 2022Article
- Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.BMJ open · 2021Article
- Carnitine palmitoyltransferase 1C negatively regulates the endocannabinoid hydrolase ABHD6 in mice, depending on nutritional status.British journal of pharmacology · 2021Article
- Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring.The international journal of neuropsychopharmacology · 2021Article
- Hypothalamic Ceramides and the Ovarian Sympathetic System: At the Crossroads of Obesity and Puberty.Cell metabolism · 2021Article
- Integration of Nutrient Sensing in Fish Hypothalamus.Frontiers in neuroscience · 2021Review
- Sample Preparation Methods for Lipidomics Approaches Used in Studies of Obesity.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Brain-specific carnitine palmitoyltransferase-1 (CPT-1c) is implicated in CNS control of food intake. In this article, we explore the role of hypothalamic CPT-1c in leptin's anorexigenic actions. We first show that adenoviral overexpression of CPT-1c in hypothalamic arcuate nucleus of rats increases food intake and concomitantly up-regulates orexigenic neuropeptide Y (NPY) and Bsx (a transcription factor of NPY). Then, we demonstrate that this overexpression antagonizes the anorectic actions induced by central leptin or compound cerulenin (an inhibitor of fatty acid synthase). The overexpression of CPT-1c also blocks leptin-induced down-regulations of NPY and Bsx. Furthermore, the anorectic actions of central leptin or cerulenin are impaired in mice with brain CPT-1c deleted. Both anorectic effects require elevated levels of hypothalamic arcuate nucleus (Arc) malonyl-CoA, a fatty acid-metabolism intermediate that has emerged as a mediator in hypothalamic control of food intake. Thus, these data suggest that CPT-1c is implicated in malonyl-CoA action in leptin's hypothalamic anorectic signaling pathways. Moreover, ceramide metabolism appears to play a role in leptin's central control of feeding. Leptin treatment decreases Arc ceramide levels, with the decrease being important in leptin-induced anorectic actions and down-regulations of NPY and Bsx. Of interest, our data indicate that leptin impacts ceramide metabolism through malonyl-CoA and CPT-1c, and ceramide de novo biosynthesis acts downstream of both malonyl-CoA and CPT-1c in mediating their effects on feeding and expressions of NPY and Bsx. In summary, we provide insights into the important roles of malonyl-CoA, CPT-1c, and ceramide metabolism in leptin's hypothalamic signaling pathways.
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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.