Adipocyte Thyroid Hormone β Receptor–Mediated Hormone Action Fine-tunes Intracellular Glucose and Lipid Metabolism and Systemic Homeostasis

Ma, Yiruo; Shen, Siyi; Yan, Ying; Zhang, Shengjie; Liu, Shengnan; Yu, Jing; Ma, Mei; Niu, Zhoumin; Li, Zhuoyang; Wu, Yuting; Zhao, Lin; Lu, Zhiqiang; Wei, Chunchun; Zhang, Weiping J.; Xue, Ying; Zhai, Qiwei; Liu, Yu; Hu, Cheng; Jiang, Jingjing; Li, Yuying; Hui, Ying

doi:10.2337/db22-0656

Cited by 17 publications

(7 citation statements)

References 42 publications

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“…Despite the benefits of β-blockers usage in many patients, there are still challenges associated with their clinical application. Some patients may experience significant adverse reactions such as bronchospasm, peripheral vasospasm, and abnormalities in glucose and lipid metabolism [ 30 , 31 ]. These adverse effects are primarily due to insufficient receptor subtype selectivity and inadequate selectivity of downstream signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation

Li,

Zhu,

Wang

et al. 2023

Bioscience Reports

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Cardiac remodeling serves as the underlying pathological basis for numerous cardiovascular diseases and represents a pivotal stage for intervention. The excessive activation of β-adrenergic receptors (β-ARs) assumes a crucial role in cardiac remodeling. Nonetheless, the underlying molecular mechanisms governing β-AR-induced cardiac remodeling remain largely unresolved. In this study, we identified Src tyrosine kinase as a key player in the cardiac remodeling triggered by excessive β-AR activation. Our findings demonstrated that Src mediates isoproterenol (ISO)-induced cardiac hypertrophy, fibrosis, and inflammation in vivo. Furthermore, Src facilitates β-AR-mediated proliferation and transdifferentiation of cardiac fibroblasts, and hypertrophy and cardiomyocytes in vitro. Subsequent investigations have substantiated that Src mediates β-AR induced the extracellular signal-regulated protein kinase (ERK1/2) signaling pathway activated by β-AR. Our research presents compelling evidence that Src promotes β-AR-induced cardiac remodeling in both in vivo and in vitro settings. It establishes the promoting effect of the β-AR/Src/ERK signaling pathway on overall cardiac remodeling in cardiac fibroblasts and underscores the potential of Src as a therapeutic target for cardiac remodeling.

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Section: Discussionmentioning

confidence: 99%

Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation

Li,

Zhu,

Wang

et al. 2023

Bioscience Reports

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“…Thyroid hormone receptor β (TRβ) in WAT interacts with ChREBP, mediating the effects of TH on various metabolic pathways. Mice lacking TRβ in adipocytes are prone to metabolic abnormalities induced by an HFD 181 . Triiodothyronine (T3) potentiates insulin signaling, enhancing insulin sensitivity, and promoting insulin synthesis.…”

Section: Wat Endocrine Remodeling and Metabolismmentioning

confidence: 99%

“…induced by an HFD. 181 Triiodothyronine (T3) potentiates insulin signaling, enhancing insulin sensitivity, and promoting insulin synthesis. These effects may contribute to its anti-diabetic properties.…”

Section: Wat Endocrine Remodeling and Mhomentioning

confidence: 99%

MHO or MUO? White adipose tissue remodeling

Zhao,

Zhou,

et al. 2024

Obesity Reviews

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SummaryIn this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). WAT is a highly heterogeneous, plastic, and dynamically secreting endocrine and immune organ. WAT remodeling plays a crucial role in metabolic health, involving expansion mode, microenvironment, phenotype, and distribution. In individuals with MHO, WAT remodeling is beneficial, reducing ectopic fat deposition and insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti‐inflammatory microenvironment, appropriate extracellular matrix (ECM) remodeling, appropriate vascularization, enhanced WAT browning, and subcutaneous adipose tissue (SWAT) deposition. Conversely, for those with MUO, WAT remodeling leads to ectopic fat deposition and IR, causing metabolic dysregulation. This process involves adipocyte hypertrophy, disrupted vascularization, heightened pro‐inflammatory microenvironment, enhanced brown adipose tissue (BAT) whitening, and accumulation of visceral adipose tissue (VWAT) deposition. The review underscores the pivotal importance of intervening in WAT remodeling to hinder the transition from MHO to MUO. This insight is valuable for tailoring personalized and effective management strategies for patients with obesity in clinical practice.

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“…In addition, very recently, Ma et al have demonstrated that systemic administration of T3 affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. They showed that TRβ is the major TR isoform that mediates the T3 action on multiple metabolic pathways in iWAT, including glucose uptake and usage, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis [101].…”

Section: The Effect Of 353 -Triiodo-l-thyronine (T3) On "Browning"mentioning

confidence: 99%

Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives

et al. 2023

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Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3′,5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as “browning”. Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance.

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Adipocyte Thyroid Hormone β Receptor–Mediated Hormone Action Fine-tunes Intracellular Glucose and Lipid Metabolism and Systemic Homeostasis

Cited by 17 publications

References 42 publications

Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation

Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation

MHO or MUO? White adipose tissue remodeling

Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives

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