ArticleMolecular metabolism2018
Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 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
- Adipose Tissue-Central Nervous System Axis in Obesity: Molecular Mechanisms, Inflammation, and Nutritional and Technological Implications.Metabolites · 2026Review
- Hypothalamic ceramide metabolism in obesity and dysregulation of glucose homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- Brain Nutrient Sensing: A Unifying Framework.Annual review of physiology · 2026Review
- Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior.Cell metabolism · 2025Article
- Western diet since adolescence impairs brain functional hyperemia at adulthood in mice: rescue by a balanced ω-3:ω-6 polyunsaturated fatty acids ratio.International journal of obesity (2005) · 2025Article
- Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Ceramides as Emerging Players in Cardiovascular Disease: Focus on Their Pathogenetic Effects and Regulation by Diet.Advances in nutrition (Bethesda, Md.) · 2024Review
- Mitochondria-Associated Membranes as Key Regulators in Cellular Homeostasis and the Potential Impact of Exercise on Insulin Resistance.International journal of molecular sciences · 2024Review
- Emerging roles of lipid and metabolic sensing in the neuroendocrine control of body weight and reproduction.Frontiers in endocrinology · 2024Review
- CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.Nature communications · 2023Article
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- Role of ceramides in diabetic foot ulcers (Review).International journal of molecular medicine · 2023Review
- Type 2 Diabetes and Alzheimer's Disease: The Emerging Role of Cellular Lipotoxicity.Biomolecules · 2023Review
- Functional consequences of brain exposure to saturated fatty acids: From energy metabolism and insulin resistance to neuronal damage.Endocrinology, diabetes & metabolism · 2023Review
- Targeting Ceramides and Adiponectin Receptors in the Islet of Langerhans for Treating Diabetes.Molecules (Basel, Switzerland) · 2022Review
- The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes.Neurochemical research · 2022Review
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Integrated lipids biomarker of the prediabetes and type 2 diabetes mellitus Chinese patients.Frontiers in endocrinology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesHypothalamic lipotoxicity has been shown to induce central insulin resistance and dysregulation of glucose homeostasis; nevertheless, elucidation of the regulatory mechanisms remains incomplete. Here, we aimed to determine the role of de novo ceramide synthesis in hypothalamus on the onset of central insulin resistance and the dysregulation of glucose homeostasis induced by obesity.
methodsHypothalamic GT1-7 neuronal cells were treated with palmitate. De novo ceramide synthesis was inhibited either by pharmacological (myriocin) or molecular (si-Serine Palmitoyl Transferase 2, siSPT2) approaches. Obese Zucker rats (OZR) were intracerebroventricularly infused with myriocin to inhibit de novo ceramide synthesis. Insulin resistance was determined by quantification of Akt phosphorylation. Ceramide levels were quantified either by a radioactive kinase assay or by mass spectrometry analysis. Glucose homeostasis were evaluated in myriocin-treated OZR. Basal and glucose-stimulated parasympathetic tonus was recorded in OZR. Insulin secretion from islets and β-cell mass was also determined.
resultsWe show that palmitate impaired insulin signaling and increased ceramide levels in hypothalamic neuronal GT1-7 cells. In addition, the use of deuterated palmitic acid demonstrated that palmitate activated several enzymes of the de novo ceramide synthesis pathway in hypothalamic cells. Importantly, myriocin and siSPT2 treatment restored insulin signaling in palmitate-treated GT1-7 cells. Protein kinase C (PKC) inhibitor or a dominant-negative PKCζ also counteracted palmitate-induced insulin resistance. Interestingly, attenuating the increase in levels of hypothalamic ceramides with intracerebroventricular infusion of myriocin in OZR improved their hypothalamic insulin-sensitivity. Importantly, central myriocin treatment partially restored glucose tolerance in OZR. This latter effect is related to the restoration of glucose-stimulated insulin secretion and an increase in β-cell mass of OZR. Electrophysiological recordings also showed an improvement of glucose-stimulated parasympathetic nerve activity in OZR centrally treated with myriocin.
conclusionOur results highlight a key role of hypothalamic de novo ceramide synthesis in central insulin resistance installation and glucose homeostasis dysregulation associated with obesity.
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.