Angiogenesis in Adipose Tissue: How can Moderate Caloric Restriction Affects Obesity-Related Endothelial Dysfunction?

Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) regulates mitochondrial DNA replication and mitochondrial gene expression by interacting with several transcription factors. White adipose tissue (WAT) mainly comprises adipocytes that store triglycerides as an energy resource and secrete adipokines. The characteristics of WAT vary in response to systemic and chronic metabolic alterations, including obesity or caloric restriction. Despite a small amount of mitochondria in white adipocytes, accumulated evidence suggests that mitochondria are strongly related to adipocyte-specific functions, such as adipogenesis and lipogenesis, as well as oxidative metabolism for energy supply. Therefore, PGC-1α is expected to play an important role in WAT. In this review, we provide an overview of the involvement of mitochondria and PGC-1α with obesity- and caloric restriction-related physiological changes in adipocytes and WAT.

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Endothelial-to-Mesenchymal Transition in Human Adipose Tissue Vasculature Alters the Particulate Secretome and Induces Endothelial Dysfunction

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.312826 ◽

2019 ◽

Vol 39 (10) ◽

pp. 2168-2191 ◽

Cited By ~ 3

Author(s):

Bronson A. Haynes ◽

Li Fang Yang ◽

Ryan W. Huyck ◽

Eric J. Lehrer ◽

Joshua M. Turner ◽

...

Keyword(s):

Adipose Tissue ◽

Endothelial Dysfunction ◽

Smooth Muscle Actin ◽

Phenotypic Change ◽

Alpha Smooth Muscle Actin ◽

Mesenchymal Transition ◽

Molecular Features ◽

Endothelial To Mesenchymal Transition

Objective: Endothelial cells (EC) in obese adipose tissue (AT) are exposed to a chronic proinflammatory environment that may induce a mesenchymal-like phenotype and altered function. The objective of this study was to establish whether endothelial-to-mesenchymal transition (EndoMT) is present in human AT in obesity and to investigate the effect of such transition on endothelial function and the endothelial particulate secretome represented by extracellular vesicles (EV). Approach and Results: We identified EndoMT in obese human AT depots by immunohistochemical co-localization of CD31 or vWF and α-SMA (alpha-smooth muscle actin). We showed that AT EC exposed in vitro to TGF-β (tumor growth factor-β), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers. The phenotypic change results in failure to maintain a tight barrier in culture, increased migration, and reduced angiogenesis. EndoMT also reduced mitochondrial oxidative phosphorylation and glycolytic capacity of EC. EVs produced by EC that underwent EndoMT dramatically reduced angiogenic capacity of the recipient naïve ECs without affecting their migration or proliferation. Proteomic analysis of EV produced by EC in the proinflammatory conditions showed presence of several pro-inflammatory and immune proteins along with an enrichment in angiogenic receptors. Conclusions: We demonstrated the presence of EndoMT in human AT in obesity. EndoMT in vitro resulted in production of EV that transferred some of the functional and metabolic features to recipient naïve EC. This result suggests that functional and molecular features of EC that underwent EndoMT in vivo can be disseminated in a paracrine or endocrine fashion and may induce endothelial dysfunction in distant vascular beds.

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The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent

Endocrine Abstracts ◽

10.1530/endoabs.77.p171 ◽

2021 ◽

Author(s):

Benjamin Thomas ◽

Karla Suckacki ◽

Claire Fyfe ◽

Adriana Tavares ◽

Richard Sulston ◽

...

Keyword(s):

Adipose Tissue ◽

Caloric Restriction ◽

Metabolic Health ◽

Age Dependent

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Whey Protein and Essential Amino Acids Promote the Reduction of Adipose Tissue and Increased Muscle Protein Synthesis During Caloric Restriction-Induced Weight Loss in Elderly, Obese Individuals

Clinical Nutrition and Aging ◽

10.1201/9781315364971-6 ◽

2017 ◽

pp. 69-86

Author(s):

Robert H. Coker ◽

Sharon Miller ◽

Scott Schutzler ◽

Nicolaas Deutz ◽

Robert R. Wolfe

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Protein Synthesis ◽

Adipose Tissue ◽

Whey Protein ◽

Caloric Restriction ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Essential Amino Acids

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Caloric Restriction Paradoxically Increases Adiposity in Mice With Genetically Reduced Insulin

Endocrinology ◽

10.1210/en.2016-1102 ◽

2016 ◽

Vol 157 (7) ◽

pp. 2724-2734 ◽

Cited By ~ 11

Author(s):

Derek A. Dionne ◽

Søs Skovsø ◽

Nicole M. Templeman ◽

Susanne M. Clee ◽

James D. Johnson

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Caloric Restriction ◽

Gene Dosage ◽

Tissue Growth ◽

Tissue Mass ◽

Brown Adipose ◽

Paradoxical Effects ◽

Plasma Insulin Levels ◽

Ad Libitum

Antiadiposity effects of caloric restriction (CR) are associated with reduced insulin/IGF-1 signaling, but it is unclear whether the effects of CR would be additive to genetically reducing circulating insulin. To address this question, we examined female Ins1+/−:Ins2−/− mice and Ins1+/+:Ins2−/− littermate controls on either an ad libitum or 60% CR diet. Although Igf1 levels declined as expected, CR was unable to reduce plasma insulin levels in either genotype below their ad libitum-fed littermate controls. In fact, 53-week-old Ins1+/−:Ins2−/− mice exhibited a paradoxical increase in circulating insulin in the CR group compared with the ad libitum-fed Ins1+/−:Ins2−/− mice. Regardless of insulin gene dosage, CR mice had lower fasting glucose and improved glucose tolerance. Although body mass and lean mass predictably fell after CR initiation, we observed a significant and unexpected increase in fat mass in the CR Ins1+/−:Ins2−/− mice. Specifically, inguinal fat was significantly increased by CR at 66 weeks and 106 weeks. By 106 weeks, brown adipose tissue mass was also significantly increased by CR in both Ins1+/−:Ins2−/− and Ins1+/+:Ins2−/− mice. Interestingly, we observed a clear whitening of brown adipose tissue in the CR groups. Mice in the CR group had altered daily energy expenditure and respiratory exchange ratio circadian rhythms in both genotypes. Multiplexed analysis of circulating hormones revealed that CR was associated with increased fasting and fed levels of the obesogenic hormone, glucose-dependent insulinotropic polypeptide. Collectively these data demonstrate CR has paradoxical effects on adipose tissue growth in the context of genetically reduced insulin.

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Periadventitial Adipose Tissue Promotes Endothelial Dysfunction via Oxidative Stress in Diet-Induced Obese C57Bl/6 Mice

Circulation Journal ◽

10.1253/circj.cj-09-0661 ◽

2010 ◽

Vol 74 (7) ◽

pp. 1479-1487 ◽

Cited By ~ 120

Author(s):

Juha Ketonen ◽

Jin Shi ◽

Essi Martonen ◽

Eero Mervaala

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Endothelial Dysfunction

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Abstract P099: Loss Of The Brown-Like Phenotype Of Aortic PVAT Is Associated With Mitochondrial Dysfunction In Obesity-Induced Endothelial Dysfunction In Female Rats

Hypertension ◽

10.1161/hyp.76.suppl_1.p099 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Nicole Maddie ◽

Maria Alicia A Carrillo-sepulveda

Keyword(s):

Adipose Tissue ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Mitochondrial Dysfunction ◽

Uncoupling Protein ◽

Obese Group ◽

Female Rats ◽

Chow Diet ◽

Anatomical Location ◽

Perivascular Adipose Tissue

Endothelial dysfunction is a major complication of obesity and is an early contributor to hypertension. Perivascular adipose tissue (PVAT) surrounds most blood vessels and has different phenotypic properties based on its anatomical location. Thoracic aortic PVAT from humans and rodents is a brown-like adipose tissue and plays a vasculo-protective role under physiological conditions. In obesity, aortic PVAT expands, switches from a brown-like to a white-like phenotype and contributes to endothelial dysfunction. We hypothesized that loss of the brown-like phenotype of aortic PVAT in obesity is associated with mitochondrial dysfunction, resulting in PVAT and endothelial dysfunction. Eight-week-old female Wistar rats were randomized into two experimental groups: the Lean group (n=8) received a chow diet (5% fat, 48.7% carbohydrate [3.2% sucrose], 24.1% protein) and the Obese group (n=8) received a western diet (21% fat, 50% carbohydrate [34% sucrose], 20% protein), for 20 weeks. Increased body weight (340.57 vs. 265.37g leans, p<0.05) was confirmed in the obese group. At the experimental endpoint, thoracic aortas with intact (+PVAT) or removed PVAT (-PVAT) were obtained for analysis. Endothelial function was assessed in aortic rings +PVAT or -PVAT by performing concentration-response to acetylcholine using wire myography. The aortic ring (-PVAT) from the obese group exhibited impaired endothelium-dependent vasodilation (p<0.01). This effect was heightened in aortic rings (+PVAT) (p<0.05), showing a negative effect of PVAT on endothelial function during obesity. Mitochondrial dysfunction in PVAT from the obese group was characterized by decreased mitochondrial density (30% reduction, p<0.05), detected by quantification of Mitotracker fluorescence, and increased reactive oxygen species levels (4.34-fold increase, p<0.01), as evidenced by DHE staining. These effects were accompanied by decreased uncoupling protein-1 expression in the obese group (55% reduction, p<0.01). Moreover, Oil Red O staining showed larger lipid droplets in aortic PVAT from the obese group. Our results support that obesity-induced endothelial dysfunction is associated with a loss of the brown-like phenotype and mitochondrial dysfunction in PVAT.

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