ArticleScientific reports2018
Diet induced obesity is independent of metabolic endotoxemia and TLR4 signalling, but markedly increases hypothalamic expression of the acute phase protein, SerpinA3N.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
- Metabolic Disorders and Inflammatory Bowel Diseases: Unraveling Shared Pathways and Clinical Interactions.Metabolites · 2026Review
- Gut microbiota and the gut-liver axis in MASLD: mechanisms, immune regulation and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- SerpinA3N in leptin-sensitive neurons is required for energy and glucose homeostasis and autonomic regulation.Metabolism: clinical and experimental · 2025Article
- Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease.Biomedicines · 2025Review
- An extra honey polyphenols-rich diet ameliorates the high-fat diet induced chronic kidney disease via modulating gut microbiota in C57BL/6 mice.Renal failure · 2024Article
- TLR4-dependent neuroinflammation mediates LPS-driven food-reward alterations during high-fat exposure.Journal of neuroinflammation · 2024Article
- Diet-Induced Obesity Induces Transcriptomic Changes in Neuroimmunometabolic-Related Genes in the Striatum and Olfactory Bulb.International journal of molecular sciences · 2024Article
- Interactions between toll-like receptors signaling pathway and gut microbiota in host homeostasis.Immunity, inflammation and disease · 2024Review
- Regulation of CNS pathology by Serpina3n/SERPINA3: The knowns and the puzzles.Neuropathology and applied neurobiology · 2024Review
- Steroid inhibited Serpina3n expression which was positively correlated with the degrees of spinal cord injury.Heliyon · 2024Article
- Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet.Frontiers in nutrition · 2024Article
- Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.Molecular biomedicine · 2023Article
- Novel Time-dependent Multi-omics Integration in Sepsis-associated Liver Dysfunction.Genomics, proteomics & bioinformatics · 2023Article
- Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal.International urology and nephrology · 2023Article
- Questioning the foundations of the gut microbiota and obesity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Palmitic Acid Modulates Microglial Cell Response to Metabolic Endotoxemia in an In Vitro Study.Nutrients · 2023Article
- RISING STARS: Endocrine regulation of metabolic homeostasis via the intestine and gut microbiome.The Journal of endocrinology · 2023Review
- SerpinA3N deficiency attenuates steatosis and enhances insulin signaling in male mice.The Journal of endocrinology · 2023Article
- Toll-like receptor 4 deletion partially protects mice from high fat diet-induced arterial stiffness despite perturbation to the gut microbiota.Frontiers in microbiomes · 2023Article
- Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases.Access microbiology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypothalamic inflammation is thought to contribute to obesity. One potential mechanism is via gut microbiota derived bacterial lipopolysaccharide (LPS) entering into the circulation and activation of Toll-like receptor-4. This is called metabolic endotoxemia. Another potential mechanism is systemic inflammation arising from sustained exposure to high-fat diet (HFD) over more than 12 weeks. In this study we show that mice fed HFD over 8 weeks become obese and show elevated plasma LPS binding protein, yet body weight gain and adiposity is not attenuated in mice lacking Tlr4 or its co-receptor Cd14. In addition, caecal microbiota composition remained unchanged by diet. Exposure of mice to HFD over a more prolonged period (20 weeks) to drive systemic inflammation also caused obesity. RNAseq used to assess hypothalamic inflammation in these mice showed increased hypothalamic expression of Serpina3n and Socs3 in response to HFD, with few other genes altered. In situ hybridisation confirmed increased Serpina3n and Socs3 expression in the ARC and DMH at 20-weeks, but also at 8-weeks and increased SerpinA3N protein could be detected as early as 1 week on HFD. Overall these data show lack of hypothalamic inflammation in response to HFD and that metabolic endotoxemia does not link HFD to obesity.
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