Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload

Liping Tian; Mohammad Jarrah; Hussein Herz; Yi Chu; Ying Xu; Yiqun Tang; Jinxiang Yuan; Mohamad Mokadem

doi:10.3390/nu15245139

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Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload

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Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload

Liping Tian, Mohammad Jarrah, Hussein Herz, Yi Chu, Ying Xu, Yiqun Tang, Jinxiang Yuan and Mohamad Mokadem

Nutrients, Vol.15(24), 5139

12/18/2023

DOI: 10.3390/nu15245139

PMCID: PMC10747341

PMID: 38140398

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Abstract

The impact of myocardial stressors such as high-fat diet (HFD) and pressure overload has been extensively studied. Toll-like receptor 4 (TLR4) deficiency has been suggested to have a protective role in response to these stressors, although some conflicting data exist. Furthermore, there is limited information about the role of TLR4 on cardiac remodeling in response to long-term exposure to stressors. This study aims to investigate the effects of TLR4 deficiency on cardiac histology and physiology in response to chronic stressors. TLR4-deficient (TLR4 ) and wild-type (WT) mice were subjected to either HFD or a normal diet (ND) for 28 weeks. Another group underwent abdominal aortic constriction (AAC) or a sham procedure and was monitored for 12 weeks. Inflammatory markers, histology, and echocardiography were used to assess the effects of these interventions. TLR4 mice exhibited reduced cardiac hypertrophy and fibrosis after long-term HFD exposure compared to ND without affecting cardiac function. On the other hand, TLR4 deficiency worsened cardiac function in response to AAC, leading to decreased ejection fraction (EF%) and increased end-systolic volume (ESV). TLR4 deficiency provided protection against HFD-induced myocardial inflammation but impaired hemodynamic cardiac function under pressure overload conditions. These findings highlight the crucial role of TLR4 and its downstream signaling pathway in maintaining cardiac output during physiologic cardiac hypertrophy in response to pressure overload.

cardiac hypertrophy

TLR4

pressure overload

Toll-like receptor

high-fat diet

Details

Title: Subtitle: Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload
Creators: Liping Tian - China Pharmaceutical University
Mohammad Jarrah - University of Iowa
Hussein Herz - University of Iowa
Yi Chu - University of Iowa
Ying Xu - China Pharmaceutical University
Yiqun Tang - China Pharmaceutical University
Jinxiang Yuan - Jining Medical University
Mohamad Mokadem - University of Iowa
Resource Type: Journal article
Publication Details: Nutrients, Vol.15(24), 5139
DOI: 10.3390/nu15245139
PMID: 38140398
PMCID: PMC10747341
eISSN: 2072-6643
Grant note: name: Outstanding Research Start-up Fund of Jining Medical University, award: 600791001P; name: Postgraduate Research & Practice Innovation Program of Jiangsu Province, award: KYCX20_0690; name: ‘The Program of Exploring World’ Student Scholarship of China Pharmaceutical University
Language: English
Date published: 12/18/2023
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984533281102771

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