ArticleThe Journal of biological chemistry2015
Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 107 citations in OpenAlex.
- Toll Like Receptor 4: A Potential Link Between Obesity and Metabolic Diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Cancer cachexia induces senescent reprogramming of brown adipose tissue and pro-cachectic S100A9 secretion by adipocytes.Cell death & disease · 2026Article
- Innate immune signalling in the adipocyte.Journal of biochemistry · 2026Review
- Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation.Journal of advanced research · 2026Article
- Article
- The role of immune responses and microbiota in adipose tissue homeostasis.The Journal of physiology · 2025Review
- Dynamics of Fatty Acid Composition in Lipids and Their Distinct Roles in Cardiometabolic Health.Biomolecules · 2025Review
- Huddling behavior regulate adaptive thermogenesis in Brandt's voles (Lasiopodomys brandtii).Cell & bioscience · 2025Article
- Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.International urology and nephrology · 2025Review
- RBM43 controls PGC1α translation and a PGC1α-STING signaling axis.Cell metabolism · 2025Article
- Apigenin promotes remodeling of peripheral and skeletal adipocytes in response to β3-AR and TLR4 activation.Frontiers in endocrinology · 2025Article
- Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcriptional control of metabolism by interferon regulatory factors.Nature reviews. Endocrinology · 2024Review
- Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation.Scientific reports · 2024Article
- TLR4 in POMC neurons regulates thermogenesis in a sex-dependent manner.Journal of lipid research · 2023Article
- The impact of metabolic endotoxaemia on the browning process in human adipocytes.BMC medicine · 2023Article
- Remodeling of Adipose Tissues by Fatty Acids: Mechanistic Update on Browning and Thermogenesis by n-3 Polyunsaturated Fatty Acids.Pharmaceutical research · 2023Review
- Omega-3 Polyunsaturated Fatty Acids Protect against High-Fat Diet-Induced Morphological and Functional Impairments of Brown Fat in TransgenicInternational journal of molecular sciences · 2022Article
- Dietary Glucose Ameliorates Impaired Intestinal Development and Immune Homeostasis Disorders Induced by Chronic Cold Stress in Pig Model.International journal of molecular sciences · 2022Article
- Comprehensive mouse microbiota genome catalog reveals major difference to its human counterpart.PLoS computational biology · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Adaptive thermogenesis is the cellular process transforming chemical energy into heat in response to cold. A decrease in adaptive thermogenesis is a contributing factor to obesity. However, the molecular mechanisms responsible for the compromised adaptive thermogenesis in obese subjects have not yet been elucidated. In this study we hypothesized that Toll-like receptor 4 (TLR4) activation and subsequent inflammatory responses are key regulators to suppress adaptive thermogenesis. To test this hypothesis, C57BL/6 mice were either fed a palmitate-enriched high fat diet or administered with chronic low-dose LPS before cold acclimation. TLR4 stimulation by a high fat diet or LPS were both associated with reduced core body temperature and heat release. Impairment of thermogenic activation was correlated with diminished expression of brown-specific markers and mitochondrial dysfunction in subcutaneous white adipose tissue (sWAT). Defective sWAT browning was concomitant with elevated levels of endoplasmic reticulum (ER) stress and autophagy. Consistently, TLR4 activation by LPS abolished cAMP-induced up-regulation of uncoupling protein 1 (UCP1) in primary human adipocytes, which was reversed by silencing of C/EBP homologous protein (CHOP). Moreover, the inactivation of ER stress by genetic deletion of CHOP or chemical chaperone conferred a resistance to the LPS-induced suppression of adaptive thermogenesis. Collectively, our data indicate the existence of a novel signaling network that links TLR4 activation, ER stress, and mitochondrial dysfunction, thereby antagonizing thermogenic activation of sWAT. Our results also suggest that TLR4/ER stress axis activation may be a responsible mechanism for obesity-mediated defective brown adipose tissue activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.