Adipose Tissue-Endothelial Cell Interactions in Obesity-Induced Endothelial Dysfunction

Li, Manna; Qian, Ming; Kyler, Kathy; Xu, Jian

doi:10.3389/fcvm.2021.681581

Cited by 17 publications

(10 citation statements)

References 132 publications

(154 reference statements)

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“…Blood vessels are lined by endothelial cells (ECs), which control the transport of nutrients, metabolites, oxygen and carbon dioxide between the blood and organs 8 . Obesity can cause global EC dysfunction, characterized by reduced nitric oxide bioavailability and increased oxidative damage 9 , 10 . However, ECs in different organs are functionally and molecularly distinct 11 , 12 .…”

Section: Mainmentioning

confidence: 99%

Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity

et al. 2022

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Obesity promotes diverse pathologies, including atherosclerosis and dementia, which frequently involve vascular defects and endothelial cell (EC) dysfunction. Each organ has distinct EC subtypes, but whether ECs are differentially affected by obesity is unknown. Here we use single-cell RNA sequencing to analyze transcriptomes of ~375,000 ECs from seven organs in male mice at progressive stages of obesity to identify organ-specific vulnerabilities. We find that obesity deregulates gene expression networks, including lipid handling, metabolic pathways and AP1 transcription factor and inflammatory signaling, in an organ- and EC-subtype-specific manner. The transcriptomic aberrations worsen with sustained obesity and are only partially mitigated by dietary intervention and weight loss. For example, dietary intervention substantially attenuates dysregulation of liver, but not kidney, EC transcriptomes. Through integration with human genome-wide association study data, we further identify a subset of vascular disease risk genes that are induced by obesity. Our work catalogs the impact of obesity on the endothelium, constitutes a useful resource and reveals leads for investigation as potential therapeutic targets.

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Section: Mainmentioning

confidence: 99%

Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity

et al. 2022

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“…However, an excessive BMI caused various other systemic diseases and complications such as hypertension (12), coronary heart disease (13), and type 2 diabetes (14). Possible mechanisms involved in the above diseases were the activation of the sympathetic nervous system (15), damage to the vascular endothelium (16), or insulin resistance (17).…”

Section: Introductionmentioning

confidence: 99%

The Saturation Effect of Body Mass Index on Bone Mineral Density for People Over 50 Years Old: A Cross-Sectional Study of the US Population

Feng

Liu

et al. 2021

Front. Nutr.

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Background: Previous studies had revealed that Body Mass Index (BMI) positively affected Bone Mineral Density (BMD). However, an excessively high BMI was detrimental to health, especially for the elderly. Moreover, it was elusive how much BMI was most beneficial for BMD in older adults to maintain.Objective: To investigate whether there was a BMI saturation effect value that existed to maintain optimal BMD.Methods: A cross-sectional study was conducted using the datasets of the National Health and Nutrition Examination Survey (NHANES) 2005–2006, 2007–2008, 2009–2010, 2013–2014, and 2017–2018. After adjusting for covariates, an analysis of the association between BMI and BMD in different femoral regions (Total femur, Femoral neck, Trochanter, Intertrochanter, and Ward's triangle) and lumbar spine regions (Total spine, L1, L2, L3, and L4) in the whole population was performed using the multivariate linear regression models, smoothing curve fitting, and saturation effects analysis models. Then, subgroup analyses were performed according to gender, age, and race.Results: A total of 10,910 participants (5,654 males and 5,256 females) over 50 years were enrolled in this population-based study. Multivariate linear regression analyses in the population older than 50 years showed that BMI was positively associated with femoral BMD and lumbar spine BMD (P < 0.001, respectively). Smoothing curve fitting showed that the relationship between BMI and BMD was not simply linear and that a saturation value existed. The saturation effect analysis showed that the BMI saturation value was 26.13 (kg/m2) in the total femur, 26.82 (kg/m2) in the total spine, and showed site-specificity in L1 (31.90 kg/m2) and L2 (30.89 kg/m2). The saturation values were consistent with the whole participants in males, while there was high variability in the females. BMI saturation values remained present in subgroup analyses by age and race, showing specificity in some age (60–70 years old) groups and in some races.Conclusions: Our study showed a saturation value association between BMI and BMD for people over 50 years old. Keeping the BMI in the slightly overweight value (around 26 kg/m2) might reduce other adverse effects while obtaining optimal BMD.

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“…Therefore, blood vessels are structurally and functionally transformed according to the systemic metabolic activity and disease state of adipose tissue. Although the mechanisms underlying the changes of blood vessels in fat are still elusive, they can be triggered by several dysfunctional modulations, such as hypoxic signals from an out-of-balance energy state and unusual expansion of adipose tissue, pro-inflammatory signals from immune cells, and fibrosis of the ECM [31,32]. In obesity, the expansion of adipose tissue causes a lack of vascular structure, which induces hypoxic signals.…”

Section: Endothelial Cellsmentioning

confidence: 99%

Engineered adipose tissue platforms: recent breakthroughs and future perspectives

Yoon

2023

Organoid

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As overweight and obesity rates have increased worldwide, the prevalence of metabolic disorders has also grown. Due to the lack of physiologically relevant adipose tissue platforms, research in adipose tissue biology has relied on animal models, leading to false conclusions on pathophysiological mechanisms and therapeutic efficacy. Despite the urgent need for an adipose tissue model, it is still extremely difficult to cultivate mature adipocytes and recapitulate multi-cellular interactions in adipose tissue in vitro. For this reason, adipose tissue modeling requires new technologies that allow better culture conditions for adipocytes and contain a complex network of microenvironments. Herein, we discuss recent technologies, including 3-dimensional (3D) adipocyte spheroids, biomaterial-based 3D culture, 3D bioprinting, and microphysiological systems, which may offer new opportunities to discover drugs targeting adipose tissue.

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Adipose Tissue-Endothelial Cell Interactions in Obesity-Induced Endothelial Dysfunction

Cited by 17 publications

References 132 publications

Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity

Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity

The Saturation Effect of Body Mass Index on Bone Mineral Density for People Over 50 Years Old: A Cross-Sectional Study of the US Population

Engineered adipose tissue platforms: recent breakthroughs and future perspectives

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