ArticleAmerican journal of physiology. Endocrinology and metabolism2010
Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 75 citations in OpenAlex.
- Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis.International journal of molecular sciences · 2022Article
- Palmitic acid-induced defects in cell cycle progression and cytokinesis in Neuro-2a cells.Cell cycle (Georgetown, Tex.) · 2022Article
- Hypothalamic inflammation in metabolic disorders and aging.Cellular and molecular life sciences : CMLS · 2021Review
- Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells.Molecular brain · 2021Article
- Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring.PLoS biology · 2020Article
- Molecular Mechanisms of Hypothalamic Insulin Resistance.International journal of molecular sciences · 2019Review
- Hypothalamic Inflammation at a Crossroad of Somatic Diseases.Cellular and molecular neurobiology · 2019Review
- Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity.Cell reports · 2018Article
- Cell culture models of fatty acid overload: Problems and solutions.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Review
- Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial Dysfunction, and Dementia.Frontiers in endocrinology · 2018Review
- One-Week Exposure to a Free-Choice High-Fat High-Sugar Diet Does Not Interfere With the Lipopolysaccharide-Induced Acute Phase Response in the Hypothalamus of Male Rats.Frontiers in endocrinology · 2018Article
- LPS-Induced Low-Grade Inflammation Increases Hypothalamic JNK Expression and Causes Central Insulin Resistance Irrespective of Body Weight Changes.International journal of molecular sciences · 2017Article
- Effects of Fat and Sugar, Either Consumed or Infused toward the Brain, on Hypothalamic ER Stress Markers.Frontiers in neuroscience · 2017Article
- Hypothalamic innate immune reaction in obesity.Nature reviews. Endocrinology · 2015Review
- Article
- Mild lipid stress induces profound loss of MC4R protein abundance and function.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.PloS one · 2014Article
- Fatting the brain: a brief of recent research.Frontiers in cellular neuroscience · 2013Review
- Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing.The Journal of biological chemistry · 2013Article
- Enteric neuropathy can be induced by high fat diet in vivo and palmitic acid exposure in vitro.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P < 0.05). By comparison, neither mixed saturated fatty acid (100, 250, or 500 microM for <or=6 h) nor palmitate exposure alone (200 microM for <or=24 h) caused inflammatory activation or insulin resistance in cultured hypothalamic neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.
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Registered trials
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