ArticlePloS one2014
Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 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
- Sodium ascorbate versus ascorbic acid in sepsis: a narrative review of emerging cardiovascular and neurological benefits.Critical care (London, England) · 2026Review
- Role of saturated fatty acid metabolism in posttranslational modifications of the Tau protein.Molecular and cellular biochemistry · 2025Review
- Lipid droplet accumulation in microglia and their potential roles.Lipids in health and disease · 2025Review
- Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases.Cancers · 2024Review
- MTCH2 cooperates with MFN2 and lysophosphatidic acid synthesis to sustain mitochondrial fusion.EMBO reports · 2024Article
- Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice.PloS one · 2024Article
- GPAM mediated lysophosphatidic acid synthesis regulates mitochondrial dynamics in acute myeloid leukemia.Cancer science · 2023Article
- From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs.Antioxidants (Basel, Switzerland) · 2023Review
- GPAT3 regulates the synthesis of lipid intermediate LPA and exacerbates Kupffer cell inflammation mediated by the ERK signaling pathway.Cell death & disease · 2023Article
- Genetic variation in satiety signaling and hypothalamic inflammation: merging fields for the study of obesity.The Journal of nutritional biochemistry · 2022Review
- Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential.International journal of molecular sciences · 2022Review
- Review
- Very long-chain acyl-CoA synthetase 3 mediates onco-sphingolipid metabolism in malignant glioma.Medical research archives · 2021Article
- Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3.Nature metabolism · 2020Article
- A Neural basis for Octanoic acid regulation of energy balance.Molecular metabolism · 2020Article
- Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring.PLoS biology · 2020Article
- TheAging · 2019Article
- Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high-fat diet in male and female mice.Journal of neurochemistry · 2019Article
- The Gut⁻Brain Axis in the Neuropsychological Disease Model of Obesity: A Classical Movie Revised by the Emerging Director "Microbiome".Nutrients · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Modification of hypothalamic fatty acid (FA) metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO) from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1) and fatty acid oxidation (FAOx), exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK) in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS), and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.
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Registered trials
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