ArticleScientific reports2018
Ageing potentiates diet-induced glucose intolerance, β-cell failure and tissue inflammation through TLR4.
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 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study.Scientific reports · 2020Trial
- Distinct macrophage and T cell programs shape pancreatic inflammation during metabolic stress and aging.bioRxiv : the preprint server for biology · 2026Article
- TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network.Nature communications · 2026Article
- The role of pancreatic islet macrophages in type 2 diabetes mellitus: from underlying pathological mechanisms to therapeutic target discovery.Metabolism open · 2025Review
- Adipose immune microenvironment: catalyst of age-related adipose tissue dysfunction.Immunity & ageing : I & A · 2025Review
- Orally ingested nanosilica causes liver-specific accumulation and induces liver senescence and fibrosis via the microbiota-gut-liver axis.Journal of nanobiotechnology · 2025Article
- Age-related decline in HMGB1-neutralizing IgM autoantibody response impairs resistance to high-fat diet in mice.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Effect of lipotoxic hepatocyte-derived extracellular vesicles in pancreas inflammation: essential role of macrophage TLR4 in beta cell functionality.Diabetologia · 2025Article
- Evaluating the prognostic significance of the modified prognostic nutritional index-C-reactive protein-to-albumin-to-lymphocyte index in acute decompensated heart failure: special attention to the impact of diabetes.Frontiers in nutrition · 2025Article
- The onset and the development of cardiometabolic aging: an insight into the underlying mechanisms.Frontiers in pharmacology · 2024Review
- Toll-like receptor 4 (TLR4): new insight immune and aging.Immunity & ageing : I & A · 2023Review
- Metabolic Score for Insulin Resistance (METS-IR) and Circulating Cytokines in Older Persons: The Role of Gender and Body Mass Index.Nutrients · 2022Article
- Sex- and strain-specific effects of mitochondrial uncoupling on age-related metabolic diseases in high-fat diet-fed mice.Aging cell · 2022Article
- Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19.Cell death and differentiation · 2021Review
- Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner.Nutrition & diabetes · 2021Article
- Aging Reduces Insulin Clearance in Mice.Frontiers in endocrinology · 2021Article
- Brain-Body Control of Glucose Homeostasis-Insights From Model Organisms.Frontiers in endocrinology · 2021Review
- Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020Review
- The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing.PLoS pathogens · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ageing and obesity are two major risk factors for the development of type 2 diabetes (T2D). A chronic, low-grade, sterile inflammation contributes to insulin resistance and β-cell failure. Toll-like receptor-4 (TLR4) is a major pro-inflammatory pathway; its ligands as well as downstream signals are increased systemically in patients with T2D and at-risk individuals. In the present study we investigated the combined effects of high fat/high sucrose diet (HFD) feeding, ageing and TLR4-deficiency on tissue inflammation, insulin resistance and β-cell failure. In young mice, a short-term HFD resulted in a mildly impaired glucose tolerance and reduced insulin secretion, together with a β-cell mass compensation. In older mice, HFD further deteriorated insulin secretion and induced a significantly impaired glucose tolerance and augmented tissue inflammation in adipose, liver and pancreatic islets, all of which was attenuated by TLR4 deficiency. Our results show that ageing exacerbates HFD-induced impairment of glucose homeostasis and pancreatic β-cell function and survival, and deteriorates HFD-induced induction of mRNA expression of inflammatory cytokines and pro-inflammatory macrophage markers. TLR4-deficiency protects against these combined deleterious effects of a high fat diet and ageing through a reduced expression of inflammatory products in both insulin sensitive tissues and pancreatic islets.
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