Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells

Cifarelli, Vincenza; Appak-Baskoy, Sıla; Peche, Vivek S.; Kluzak, Andrew; Shew, Trevor M.; Narendran, Ramkumar; Pietka, Kathryn M.; Cella, Marina; Walls, Curtis W.; Czepielewski, Rafael S.; Ivanov, Stoyan; Randolph, Gwendalyn J.; Augustin, Hellmut G.; Abumrad, Nada A.

doi:10.1038/s41467-021-23808-3

Cited by 83 publications

(81 citation statements)

References 73 publications

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“…Inflammation can lead to increased permeability of lymphatic vessels and increase the volume of interstitial fluid [ 157 , 158 , 159 , 160 ]. Increasing its volume causes stretching of the lymphatic vessel wall, which contributes to increasing the frequency and/or force of lymphangion contractions and to the increase the lymphangio-motoric activity to prevent oedema development [ 134 , 135 ].…”

Section: Dysfunction Of the Lymphatic System: Pro- And Anti-lymphangiogenic Factors In Obesitymentioning

confidence: 99%

“…In a study by Ciffarelli et al, an attempt was made to assess the relationship between the level of lymphatic permeability and the time of lipid transport in the intestinal lactic vessels [ 159 ]. For this purpose, male and female mice divided into two groups were included in the study.…”

Section: Dysfunction Of the Lymphatic System: Pro- And Anti-lymphangiogenic Factors In Obesitymentioning

confidence: 99%

“…In both groups, a high-fat diet was used for 12 weeks, body weight was determined, an oral glucose load test was performed, and the function of lymphatic vessels was analysed. It has been shown that, along with the increased permeability of the intestinal lactic vessels (Cd36ΔLEC mice), slower transport of absorbed lipids is observed, and in addition increased VAT accumulation, increased inflammation and decreased glucose tolerance were observed [ 159 ].…”

Section: Dysfunction Of the Lymphatic System: Pro- And Anti-lymphangiogenic Factors In Obesitymentioning

confidence: 99%

“…They utilized in vitro assays of the lymphatic endothelial cell (LEC) monolayer barrier function after treatment with different inflammatory cytokines and signalling molecules including TNF-α, IL-6, IL-1β, IFN-γ and LPS. Moderate increases in an index of monolayer barrier dysfunction were noted In a study by Ciffarelli et al, an attempt was made to assess the relationship between the level of lymphatic permeability and the time of lipid transport in the intestinal lactic vessels [159]. For this purpose, male and female mice divided into two groups were included in the study.…”

Section: Lymphatic System Dysfunctions-permeability Of Lymphatic Vesselsmentioning

confidence: 99%

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Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity

et al. 2021

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The World Health Organization (WHO) has recognised obesity as one of the top ten threats to human health. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of an increased release of biologically active metabolites. Moreover, obesity predisposes the development of metabolic syndrome and increases the incidence of type 2 diabetes (T2DM), increases the risk of developing insulin resistance, atherosclerosis, ischemic heart disease, polycystic ovary syndrome, hypertension and cancer. The lymphatic system is a one-directional network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells that provides a unidirectional conduit to return filtered arterial and tissue metabolites towards the venous circulation. Recent studies have shown that obesity can markedly impair lymphatic function. Conversely, dysfunction in the lymphatic system may also be involved in the pathogenesis of obesity. This review highlights the important findings regarding obesity related to lymphatic system dysfunction, including clinical implications and experimental studies. Moreover, we present the role of biological factors in the pathophysiology of the lymphatic system and we propose the possibility of a therapy supporting the function of the lymphatic system in the course of obesity.

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Section: Dysfunction Of the Lymphatic System: Pro- And Anti-lymphangiogenic Factors In Obesitymentioning

confidence: 99%

Section: Dysfunction Of the Lymphatic System: Pro- And Anti-lymphangiogenic Factors In Obesitymentioning

confidence: 99%

Section: Dysfunction Of the Lymphatic System: Pro- And Anti-lymphangiogenic Factors In Obesitymentioning

confidence: 99%

Section: Lymphatic System Dysfunctions-permeability Of Lymphatic Vesselsmentioning

confidence: 99%

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Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity

et al. 2021

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“…В свою очередь, делеция гена-транспортера жирных кислот CD36/FAT дестабилизировала «пуговичные» межклеточные соединения между эндотелиоцитами, тормозила окисление жирных кислот, сигналинг VEGF-C и лимфангиогенез. В условиях in vivo это повышало проницаемость «млечных» сосудов, отходящих от кишечника, что вызывало «утечку» богатой хиломикронами лимфы, воспаление висцеральной ЖТ и развитие ожирения [59].…”

Section: взаимодействия между лимфатической системой и жировой тканью при ожиренииunclassified

Lymphatic system and adipose tissue: Crosstalk in health and disease

Климонтов

Bulumbaeva

2021

Obes. metabol.

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The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

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Psychosocial Disadvantage During Childhood and Midlife Health

Brown,

Alegria,

Hamlat

et al. 2024

JAMA Netw Open

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ImportanceLow childhood socioeconomic status (SES) is a social hallmark of aging that contributes to adult health disparities and earlier morbidity and mortality. Childhood perceptions of stress are associated with child health outcomes and may contribute to premature biological aging into adulthood.ObjectiveTo describe the association of childhood SES and perceived stress with midlife insulin resistance and epigenetic age and to explore whether late adolescent adiposity mediates the observed associations.Design, Setting, and ParticipantsThe longitudinal cohort National Heart, Lung, and Blood Institute Growth and Health Study enrolled girls aged 10 years from January 1987 to May 1988, and followed them up to 19 years of age. Participants from Richmond, California, were recruited again at midlife in 2016 to assess insulin resistance and epigenetic age. Analyses were conducted from August 2, 2023, to March 18, 2024. A total of 433 participants were eligible and included in the analyses (specific sample sizes ranged across analyses from 303 to 391).ExposuresChildhood levels of SES at 10 years of age (parental educational level and income) and perceived stress at 11 years of age.Main Outcomes and MeasuresThe hypotheses tested were formulated after data collection. Outcomes included the homeostatic model assessment of insulin resistance (HOMA-IR) and the GrimAge and DunedinPACE epigenetic clocks. Waist circumference in late adolescence was tested as a mediator.ResultsAmong the 433 participants, the mean (SD) age was 39.4 (1.2) years; 218 (50.3%) were Black and 215 (49.7%) were White; and 135 (31.2%) had parents with a college degree or higher. Higher parental educational level was associated with lower HOMA-IR (B = −0.22 [95% CI, −0.41 to −0.02]; P = .03), lower midlife GrimAge (B = −1.76 [95% CI, −2.85 to −0.66] years; P = .002), and slower midlife DunedinPACE (B = −0.03 [95% CI, −6.29 to −0.002]; P = .04). Childhood perceived stress was indirectly associated through late adolescent adiposity with midlife HOMA-IR (B = 0.01 [95% CI, 0.001-0.01]; P = .02) and midlife GrimAge (B = 0.02 [95% CI, 0.003-0.04] years; P = .01).Conclusions and RelevanceIn this longitudinal cohort study of midlife health and aging, childhood social hallmarks of aging were associated with midlife insulin resistance and epigenetic age (GrimAge and DunedinPACE). Future studies should identify malleable factors that may slow the impact of social hallmarks of aging.

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Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells

Cited by 83 publications

References 73 publications

Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity

Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity

Lymphatic system and adipose tissue: Crosstalk in health and disease

Psychosocial Disadvantage During Childhood and Midlife Health

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