ArticleAmerican journal of physiology. Endocrinology and metabolism2018
Saturated fatty acid combined with lipopolysaccharide stimulates a strong inflammatory response in hepatocytes in vivo and in vitro.
Article in American journal of physiology. Endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Nobiletin Attenuates Inflammation and Modulates Lipid Metabolism in an In Vitro Model of Intestinal Failure-Associated Liver Disease.Pharmaceutics · 2026Article
- Decoding the CHI3L1/IL-13Rα2 signaling nexus in MASH-fibrosis pathogenesis.Science advances · 2025Article
- GPAM upregulation enhances hepatic fat deposition and reduces visceral adipose tissue in response to trans-fatty acids.Journal of gastroenterology · 2025Article
- Adherence to the planetary health diet index and metabolic dysfunction-associated steatotic liver disease: a cross-sectional study.Frontiers in nutrition · 2025Article
- Dietary Influences on Gut Microbiota and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Nutrients · 2024Review
- SPTLC3 regulates plasma membrane sphingolipid composition to facilitate hepatic gluconeogenesis.Cell reports · 2024Article
- Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus.Nutrients · 2023Review
- Liver saturated fat content associates with hepatic DNA methylation in obese individuals.Clinical epigenetics · 2023Article
- Caspase-11 promotes high-fat diet-induced NAFLD by increasing glycolysis, OXPHOS, and pyroptosis in macrophages.Frontiers in immunology · 2023Article
- Promoting intestinal antimicrobial defense and microbiome symbiosis contributes to IL-22-mediated protection against alcoholic hepatitis in mice.Frontiers in immunology · 2023Article
- TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis.Nature communications · 2022Article
- The Impact of Diet on Bone and Fracture Risk in Diabetes.Current osteoporosis reports · 2022Review
- Article
- Mesenchymal stromal cells protect hepatocytes from lipotoxicity through alleviation of endoplasmic reticulum stress by restoring SERCA activity.Journal of cellular and molecular medicine · 2021Article
- Cellular and molecular effects of silymarin on the transdifferentiation processes of LX-2 cells and its connection with lipid metabolism.Molecular and cellular biochemistry · 2020Article
- Orotic acid-treated hepatocellular carcinoma cells resist steatosis by modification of fatty acid metabolism.Lipids in health and disease · 2020Article
- Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism.American journal of physiology. Endocrinology and metabolism · 2020Article
- Article
- Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in macrophages and hepatocytes.PloS one · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and consumption of high-fat diet (HFD) is a risk factor for NAFLD. The HFD not only increases intake of saturated fatty acid (SFA) but also induces metabolic endotoxemia, an HFD-associated increase in circulating lipopolysaccharide (LPS). Although it is known that SFA or LPS promote hepatic inflammation, a hallmark of NAFLD, it remains unclear how SFA in combination with LPS stimulates host inflammatory response in hepatocytes. In this study, we performed both in vivo and in vitro experiments to investigate the effect of SFA in combination with LPS on proinflammatory gene expression in hepatocytes. Our animal study showed that feeding low-density lipoprotein-deficient mice HFD enriched with SFA and injection of low-dose LPS cooperatively stimulated IL-6 expression in livers. To understand how SFA and LPS interact to promote IL-6 expression, our in vitro studies showed that palmitic acid (PA), a major SFA, and LPS exerted synergistic effect on the expression of IL-6 in hepatocytes. Furthermore, coculture of hepatocytes with macrophages resulted in a greater IL-6 expression than culture of hepatocytes without macrophages in response to the combination of PA and LPS. Finally, we observed that LPS and PA increased ceramide production by cooperatively stimulating ceramide de novo synthesis, which played an essential role in the synergistic stimulation of proinflammatory gene expression by LPS and PA. Taken together, this study showed that SFA in combination with LPS stimulated a strong inflammatory response in hepatocytes in vivo and in vitro.
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