ArticleThe Journal of clinical investigation2009
Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 146 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
146 citing papers in PubMed, 2 syntheses or guidelines pooled it, 340 citations in OpenAlex.
- Plant-based diet and risk of all-cause mortality: a systematic review and meta-analysis.Frontiers in nutrition · 2024Pooled it
- Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023Pooled it
- High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention.Diabetologia · 2012Trial
- Autophagy in hypothalamic POMC and AgRP neurons: mechanisms and therapeutic implications for obesity.International journal of obesity (2005) · 2026Review
- Cortical-Hypothalamic Assembloids Uncover the Cortical Regulation of Hypothalamic Responses to Fatty Acid.Cell proliferation · 2026Article
- Palmitic acid-induced autolysosomal dysfunction and lipotoxicity in neuroinflammation and neurodegeneration.Neural regeneration research · 2026Article
- Redefining the timeline: a three-phase framework of hypothalamic microinflammation in metabolic disease.Reviews in endocrine & metabolic disorders · 2026Review
- Brain Nutrient Sensing: A Unifying Framework.Annual review of physiology · 2026Review
- Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Maternal Obesity in Pregnancy: Risk Factor for Neurodevelopmental Outcomes in Offspring.Journal of neurochemistry · 2025Review
- Differences in the Effects of Saturated and Trans Fatty Acids on Metabolism and Anxiety-Like Behavior in Mice.Food science & nutrition · 2025Article
- An interoceptive model of energy allostasis linking metabolic and mental health.Science advances · 2025Review
- Role of saturated fatty acid metabolism in posttranslational modifications of the Tau protein.Molecular and cellular biochemistry · 2025Review
- Palmitic Acid Induces Dynamic Time-Dependent Alterations in HDACs, Neuronal Chromatin Acetylation, and Gene Expression.Neurochemical research · 2025Article
- PEX11B palmitoylation couples peroxisomal dysfunction with Schwann cells fail in diabetic neuropathy.Journal of biomedical science · 2025Article
- Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.Nature communications · 2025Article
- Uncovering the heterogeneity of the gut microbial taxa associated with the contents of different fatty acids in muscle with cecum luminal content and fecal samples from two pig populations.Frontiers in microbiology · 2025Article
- Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT.Experimental & molecular medicine · 2024Article
- Palmitic Acid Induces Posttranslational Modifications of Tau Protein in Alzheimer's Disease-Related Epitopes and Increases Intraneuronal Tau Levels.Molecular neurobiology · 2024Article
- Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity.Clinical nutrition research · 2024Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.
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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.