The Lymphatic System in Obesity, Insulin Resistance, and Cardiovascular Diseases

Jiang, Xinguo; Tian, Wen; Nicolls, Mark R.; Rockson, Stanley G.

doi:10.3389/fphys.2019.01402

Cited by 50 publications

(46 citation statements)

References 124 publications

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“…Previous reviews covered several aspects of obesity and its implication on lymphatic vessels in relation to different pathologies like lymphedema and metabolic disorders (Escobedo and Oliver, 2017;Jiang et al, 2019;Ho and Srinivasan, 2020). This article emphasizes on the bidirectional interaction between obesity and lymphatic function.…”

Section: Introduction Lymphatic Anatomy and Physiologymentioning

confidence: 99%

Regulation of Lymphatic Function in Obesity

et al. 2020

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The lymphatic system has many functions, including macromolecules transport, fat absorption, regulation and modulation of adaptive immune responses, clearance of inflammatory cytokines, and cholesterol metabolism. Thus, it is evident that lymphatic function can play a key role in the regulation of a wide array of biologic phenomenon, and that physiologic changes that alter lymphatic function may have profound pathologic effects. Recent studies have shown that obesity can markedly impair lymphatic function. Obesity-induced pathologic changes in the lymphatic system result, at least in part, from the accumulation of inflammatory cells around lymphatic vessel leading to impaired lymphatic collecting vessel pumping capacity, leaky initial and collecting lymphatics, alterations in lymphatic endothelial cell (LEC) gene expression, and degradation of junctional proteins. These changes are important since impaired lymphatic function in obesity may contribute to the pathology of obesity in other organ systems in a feedforward manner by increasing low-grade tissue inflammation and the accumulation of inflammatory cytokines. More importantly, recent studies have suggested that interventions that inhibit inflammatory responses, either pharmacologically or by lifestyle modifications such as aerobic exercise and weight loss, improve lymphatic function and metabolic parameters in obese mice. The purpose of this review is to summarize the pathologic effects of obesity on the lymphatic system, the cellular mechanisms that regulate these responses, the effects of impaired lymphatic function on metabolic syndrome in obesity, and the interventions that may improve lymphatic function in obesity.

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Section: Introduction Lymphatic Anatomy and Physiologymentioning

confidence: 99%

Regulation of Lymphatic Function in Obesity

et al. 2020

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“…It is known that the conditions that have been discussed in this article as contributors in the pathogenesis of acne or acne associated factors such as Western diet, activation of mTORC1 signaling, insulin resistance, dyslipidemia, increased WC, high values of BP, and fasting blood glucose, are also related with the development of cardiovascular diseases (CVD) 35 . All these factors are triggers of each other in a vicious cycle which may end up with CVD.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of serum FoxO1 , mTORC1 , IGF ‐1, IGFBP ‐3 levels, and metabolic syndrome components in patients with acne vulgaris: A prospective case‐control study

Karabay¹,

Saltık

Demirel

2020

Dermatologic Therapy

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Recently, insulin-like growth factor-1 (IGF-1), forkhead box transcription factor (Fox) O1, and mechanistic target of rapamycin complex 1 (mTORC1) signaling have been introduced as key elements in acne pathogenesis. The aim of this study is to investigate the relationship between serum levels of IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), FoxO1 and mTORC1, and the components of metabolic syndrome (MS) and AV. This prospective case-control study was carried out on 89 participants, including 49 AV patients and 40 controls. The serum levels of IGF-1, IGFBP-3, insulin, FoxO1, and mTORC1 were measured along with the components of MS. The blood pressure (BP) measures were significantly higher in the AV patients than in the controls (P = .001). The mean high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in the AV patients than in the controls (P = .040).

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“…Given the plasticity of specialized lymphatic endothelial cell junctions, zipper- and button-like junctions are tightly maintained to keep lymphatic vessel integrity and function for tissue homeostasis. It has become increasingly evident that disrupted LEC junctions are potentially associated with various diseases, including lymphatic leakage present in chylothorax and lymphedema, metabolic syndrome, and impaired immune surveillance (Cifarelli and Eichmann, 2019 ; Jiang et al, 2019 ; Xiao et al, 2019 ; Norden and Kume, 2020 ; Zhang et al, 2020 ). The recent seminal studies summarized in this review provide compelling evidence that RhoA/ROCK signaling regulates LEC junction integrity in different vascular beds (Zhang et al, 2018 ; Hisano et al, 2019 ; Frye et al, 2020 ; Norden et al, 2020 ) ( Table 1 , Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Controlling Lymphatic Endothelial Junction Integrity

Norden

Kume

2021

Front. Cell Dev. Biol.

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The lymphatic system is essential for lipid absorption/transport from the digestive system, maintenance of tissue fluid and protein homeostasis, and immune surveillance. Despite recent progress toward understanding the cellular and molecular mechanisms underlying the formation of the lymphatic vascular system, the nature of lymphatic vessel abnormalities and disease in humans is complex and poorly understood. The mature lymphatic vasculature forms a hierarchical network in which lymphatic endothelial cells (LECs) are joined by functionally specialized cell-cell junctions to maintain the integrity of lymphatic vessels. Blind-ended and highly permeable lymphatic capillaries drain interstitial fluid via discontinuous, button-like LEC junctions, whereas collecting lymphatic vessels, surrounded by intact basement membranes and lymphatic smooth muscle cells, have continuous, zipper-like LEC junctions to transport lymph to the blood circulatory system without leakage. In this review, we discuss the recent advances in our understanding of the mechanisms by which lymphatic button- and zipper-like junctions play critical roles in lymphatic permeability and function in a tissue- and organ-specific manner, including lacteals of the small intestine. We also provide current knowledge related to key pathways and factors such as VEGF and RhoA/ROCK signaling that control lymphatic endothelial cell junctional integrity.

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The Lymphatic System in Obesity, Insulin Resistance, and Cardiovascular Diseases

Cited by 50 publications

References 124 publications

Regulation of Lymphatic Function in Obesity

Regulation of Lymphatic Function in Obesity

Evaluation of serum FoxO1 , mTORC1 , IGF ‐1, IGFBP ‐3 levels, and metabolic syndrome components in patients with acne vulgaris: A prospective case‐control study

Molecular Mechanisms Controlling Lymphatic Endothelial Junction Integrity

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