The Role of TLRs in Obesity and Its Related Metabolic Disorders

Obesity affects the adaptability of adipose tissue (AT), impairing its ability to regulate energy and metabolism. Obesity is associated with many metabolic disorders, including dyslipidemia, hypertension, sleep disorders, non-alcoholic liver disease, and some types of cancer. Toll-like receptors (TLRs) are important in obesity and related metabolic disorders. TLRs are pattern-recognizing receptors (PRRs) involved in the innate immune system and recognize pathogen-associated molecular patterns (PAMPs) and endogenous ligands. TLRs, especially TLR2 and TLR4, are activated by fatty acids, endotoxins, and other ligands. TLR2 and TLR4 activation triggers inflammatory responses. Chronic inflammation driven by TLR activation is a hallmark of obesity and metabolic diseases. The inflammatory response triggered by TLR activation alters insulin signaling, contributing to insulin resistance, a key feature of metabolic syndrome and type 2 diabetes. Modulation of TLR activity through lifestyle changes (diet and exercise), obesity surgery, and pharmacological agents is under study as a possible therapeutic approach to controlling obesity and its complications.

• Publication year

  2025

• Venue

  International Journal of Molecular Sciences

• Publication date

  2025-03-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3390/ijms26052229PMID 40076851PMCID 11900219
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Practical Lifestyle Management of Nonalcoholic Fatty Liver Disease for Busy Clinicians

  2024influential reference
• Omega‐3 polyunsaturated fatty acids in the treatment of non‐alcoholic fatty liver disease: An umbrella systematic review and meta‐analysis

  2023cited by this paper
• Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders.

  2023cited by this paper
• Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

  2023cited by this paper
• Induction of TLR4/TLR2 Interaction and Heterodimer Formation by Low Endotoxic Atypical LPS

  2022cited by this paper
• Opposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity

  2022cited by this paper
• Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

  2022cited by this paper
• Inflammation in obesity, diabetes, and related disorders.

  2022cited by this paper
• The effect of omega-3 fatty acid supplementation on weight loss and cognitive function in overweight or obese individuals on weight-loss diet.

  2022cited by this paper
• Adipose tissue and insulin resistance in obese.

  2021influential reference
• Blocking TLR4-NF-κB pathway protects mouse islets from the combinatorial impact of high fat and fetuin-A mediated dysfunction and restores ability for insulin secretion.

  2021cited by this paper
• Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

  2021cited by this paper
• Understanding the Effects of Gut Microbiota Dysbiosis on Nonalcoholic Fatty Liver Disease and the Possible Probiotics Role: Recent Updates

  2021cited by this paper
• Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) in Innate Immunity. TLRs, NLRs, and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases

  2021cited by this paper
• The type 2 diabetes ‘modern preventable pandemic’ and replicable lessons from the COVID-19 crisis

  2021cited by this paper
• Role of TLR4 in the induction of inflammatory changes in adipocytes and macrophages

  2020cited by this paper
• Prevention of Cardiovascular Events with Omega-3 Polyunsaturated Fatty Acids and the Mechanism Involved

  2020cited by this paper
• Saturated Fatty Acids in Obesity-Associated Inflammation

  2020cited by this paper
• Effects of the Ketogenic Diet on Glycemic Control in Diabetic Patients: Meta-Analysis of Clinical Trials

  2020cited by this paper
• Adipose Tissue Inflammation and Metabolic Dysfunction in Obesity.

  2020cited by this paper
• Infection and atherosclerosis: TLR-dependent pathways

  2020influential reference
• Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

  2020cited by this paper
• Metabolic inflammation - a role for hepatic inflammatory pathways as driver of comorbidities in non-alcoholic fatty liver disease (NAFLD)?

  2020cited by this paper
• Adipose tissue density on CT as a prognostic factor in patients with cancer: a systematic review

  2020cited by this paper
• Nonalcoholic Fatty Liver Disease and Obesity Treatment

  2019cited by this paper
• Obesity: global epidemiology and pathogenesis

  2019cited by this paper
• A global perspective on the crosstalk between saturated fatty acids and Toll-like receptor 4 in the etiology of inflammation and insulin resistance.

  2019cited by this paper
• Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links.

  2019cited by this paper
• Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

  2019cited by this paper
• The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives

  2018cited by this paper
• Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

  2018cited by this paper
• [Management of non-alcoholic fatty liver disease].

  2018cited by this paper
• Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation

  2018cited by this paper
• Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study.

  2018cited by this paper
• Palmitate Activates CCL4 Expression in Human Monocytic Cells via TLR4/MyD88 Dependent Activation of NF-κB/MAPK/ PI3K Signaling Systems

  2018cited by this paper
• Infections, atherosclerosis, and coronary heart disease.

  2017cited by this paper
• The Role of Toll-Like Receptors and Vitamin D in Cardiovascular Diseases—A Review

  2017cited by this paper
• Toll-like receptor stimulation in cancer: A pro- and anti-tumor double-edged sword.

  2017cited by this paper
• Inflammation, metaflammation and immunometabolic disorders

  2017cited by this paper
• mTOR Signaling in Growth, Metabolism, and Disease.

  2017cited by this paper
• Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases

  2017cited by this paper
• Leukocyte TLR5 deficiency inhibits atherosclerosis by reduced macrophage recruitment and defective T-cell responsiveness

  2017cited by this paper
• Epigenetic and Transcriptional Regulation of IRAK-M Expression in Macrophages

  2017cited by this paper
• Foundations of Immunometabolism and Implications for Metabolic Health and Disease.

  2017cited by this paper
• Monocyte-Macrophages and T Cells in Atherosclerosis.

  2017cited by this paper
• Toll-like receptor 2 and type 2 diabetes

  2016cited by this paper
• Saturated fatty acids trigger TLR4-mediated inflammatory response.

  2016cited by this paper
• Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease

  2016influential reference
• TLR signalling and association of TLR polymorphism with cardiovascular diseases.

  2016cited by this paper
• Increased adipose tissue expression of TLR8 in obese individuals with or without type-2 diabetes: significance in metabolic inflammation

  2016cited by this paper
• Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes

  2016cited by this paper
• ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue

  2016cited by this paper
• Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis.

  2016cited by this paper
• Toll-like receptor (TLR)-2/4 expression in retinal ganglion cells in a high-glucose environment and its implications.

  2016cited by this paper
• Is Obesity Associated with Altered Energy Expenditure?

  2016cited by this paper
• Pterostilbene, a novel natural plant conduct, inhibits high fat-induced atherosclerosis inflammation via NF-κB signaling pathway in Toll-like receptor 5 (TLR5) deficient mice.

  2016cited by this paper
• Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact

  2016cited by this paper
• Vascular Smooth Muscle Cells in Atherosclerosis.

  2016cited by this paper
• Expression of toll‐like receptors 1–5 but not TLR 6–10 is elevated in livers of patients with non‐alcoholic fatty liver disease

  2015influential reference
• Toll-Like Receptor 3 Influences Glucose Homeostasis and β-Cell Insulin Secretion

  2015cited by this paper
• Fatty Acids, Obesity and Insulin Resistance

  2015cited by this paper
• 3T3-L1 adipocytes display phenotypic characteristics of multiple adipocyte lineages

  2015cited by this paper
• TLR-3 is Present in Human Adipocytes, but Its Signalling is Not Required for Obesity-Induced Inflammation in Adipose Tissue In Vivo

  2015cited by this paper
• Paying the Toll for Glucose Regulation: A Central Role for TLR3

  2015cited by this paper
• Nonalcoholic fatty liver disease: a systematic review.

  2015cited by this paper
• High Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

  2014cited by this paper
• The concept of normal weight obesity.

  2014cited by this paper
• Assembly and localization of Toll-like receptor signalling complexes

  2014cited by this paper
• Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance.

  2014influential reference
• A Role for the Adaptor Proteins TRAM and TRIF in Toll-like Receptor 2 Signaling*

  2014cited by this paper
• Insights Into the Role of the Microbiome in Obesity and Type 2 Diabetes

  2014cited by this paper
• Active Invasion of Oral and Aortic Tissues by Porphyromonas gingivalis in Mice Causally Links Periodontitis and Atherosclerosis

  2014cited by this paper
• Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes.

  2014cited by this paper
• High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

  2014cited by this paper
• Toll-like receptor agonists: a patent review (2011 – 2013)

  2014cited by this paper
• Acyl-Coenzyme A–Binding Protein Regulates Beta-Oxidation Required for Growth and Survival of Non–Small Cell Lung Cancer

  2014cited by this paper
• Protective Role for Toll-Like Receptor-9 in the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice

  2014cited by this paper
• Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults

  2014cited by this paper
• Toll‐like receptor 2/4 links to free fatty acid‐induced inflammation and β‐cell dysfunction

  2014cited by this paper
• Recognition of lipopolysaccharide pattern by TLR4 complexes

  2013cited by this paper
• Adipose tissue macrophages in the development of obesity-induced inflammation, insulin resistance and type 2 Diabetes

  2013cited by this paper
• Toll‐like receptors in alcoholic liver disease, non‐alcoholic steatohepatitis and carcinogenesis

  2013cited by this paper
• Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRASG12D-driven lung tumors

  2013cited by this paper
• Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

  2013cited by this paper
• TLR3 deficiency protects against collagen degradation and medial destruction in murine atherosclerotic plaques.

  2013cited by this paper
• Adipose tissue and adipocytes support tumorigenesis and metastasis.

  2013cited by this paper
• Hypothalamic neuronal toll-like receptor 2 protects against age-induced obesity

  2013cited by this paper
• The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes: A Pooled Analysis

  2013cited by this paper
• Central nervous system control of metabolism

  2012cited by this paper
• TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipidinduced inflammation and insulin resistance in muscle cells

  2012cited by this paper
• Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice.

  2012influential reference
• TNF-α up-regulates protein level and cell surface expression of the leptin receptor by stimulating its export via a PKC-dependent mechanism.

  2012cited by this paper
• Genetic variation within TLR10 is associated with Crohn's disease in a New Zealand population.

  2012cited by this paper
• Toll-Like Receptor 7 Protects From Atherosclerosis by Constraining “Inflammatory” Macrophage Activation

  2012cited by this paper
• Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association.

  2012cited by this paper
• Toll-like receptors 1-9 are elevated in livers with fructose-induced hepatic steatosis.

  2012cited by this paper
• Toll-Like Receptor 4 Deficiency Decreases Atherosclerosis But Does Not Protect Against Inflammation in Obese Low-Density Lipoprotein Receptor–Deficient Mice

  2012cited by this paper
• Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut

  2012cited by this paper
• The cellular and signaling networks linking the immune system and metabolism in disease

  2012cited by this paper
• Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation

  2012cited by this paper

• Diagnostic Utility of Serum Activating Transcription Factor 4 and Toll-like Receptor 4 as Early Biomarkers of Inflammation in Metabolic Dysfunction–Associated Steatotic Liver Disease

  2026cites this paper
• Pharmacological silence: Revisiting the clinical and molecular impact of inactive metabolites.

  2026cites this paper
• Sex Differences in the Impact of Obesity on Immunity.

  2026cites this paper
• Dietary polyphenols targeting NLRP3 inflammasome in obesity and metabolic disorders: a review on experimental and computational evidence.

  2026cites this paper
• High intensity functional training versus traditional resistance training effects on inflammatory, metabolic, and physical outcomes in overweight men a randomized controlled trial.

  2026cites this paper
• Beneficial effects of long-chain n-3 fatty acids on insulin-resistance: basic and clinical aspects.

  2025cites this paper
• Role of Antioxidants in Modulating the Microbiota–Gut–Brain Axis and Their Impact on Neurodegenerative Diseases

  2025cites this paper
• Engineered exosome-mediated delivery of MicroRNA let-7i-5p targets toll-like receptor 4 to modulate inflammation and alleviate acute liver injury in septic mice.

  2025cites this paper
• Obesity as a mediator in the association between urinary polycyclic aromatic hydrocarbon exposure and liver fibrosis risk in US adults.

  2025cites this paper
• Key Roles of Brown, Subcutaneous, and Visceral Adipose Tissues in Obesity and Insulin Resistance

  2025cites this paper
• Complex interaction of waist circumference, cardiometabolic markers, and sex on elderly mortality: a cohort study of 0.4 million UK adults

  2025cites this paper
• Synergistic effects of NF-κB1 and inflammatory pathway polymorphisms on hypertension and dyslipidemia susceptibility in type 2 diabetes

  2025cites this paper