Effect ofDanhongon metabolism and vascular function of rats with high-fat diet-induced spontaneous hypertension

Clinical studies have shown that obesity negatively impacts large arteries’ function. We reported that rats exposed to maternal separation (MatSep), a model of early life stress, display enhanced angiotensin II (ANG II)-induced vasoconstriction in aortic rings cleaned of perivascular adipose tissue (PVAT) under normal diet (ND) conditions. We hypothesized that exposure to MatSep promotes a greater loss of PVAT-mediated protective effects on vascular function and loss of blood pressure (BP) rhythm in rats fed a high-fat diet (HFD) when compared with controls. MatSep was performed in male Wistar-Kyoto rats from days 2 to 14 of life. Normally reared littermates served as controls. On ND, aortic rings from MatSep rats with PVAT removed showed increased ANG II-mediated vasoconstriction versus controls; however, rings from MatSep rats with intact PVAT displayed blunted constriction. This effect was exacerbated by an HFD in both groups; however, the anticontractile effect of PVAT was greater in MatSep rats. Acetylcholine-induced relaxation was similar in MatSep and control rats fed an ND, regardless of the presence of PVAT. HFD impaired aortic relaxation in rings without PVAT from MatSep rats, whereas the presence of PVAT improved relaxation in both groups. On an HFD, immunolocalization of vascular smooth muscle-derived ANG-(1–7) and PVAT-derived adiponectin abundances were increased in MatSep. In rats fed an HFD, 24-h BP and BP rhythms were similar between groups. In summary, MatSep enhanced the ability of PVAT to blunt the heightened ANG II-induced vasoconstriction and endothelial dysfunction in rats fed an HFD. This protective effect may be mediated via the upregulation of vasoprotective factors within the adipovascular axis.

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Unacylated Ghrelin Improves Vascular Dysfunction and Attenuates Atherosclerosis during High-Fat Diet Consumption in Rodents

International Journal of Molecular Sciences ◽

10.3390/ijms20030499 ◽

2019 ◽

Vol 20 (3) ◽

pp. 499 ◽

Cited By ~ 6

Author(s):

Michela Zanetti ◽

Gianluca Gortan Cappellari ◽

Andrea Graziani ◽

Rocco Barazzoni

Keyword(s):

Oxidative Stress ◽

Lipid Accumulation ◽

High Fat Diet ◽

Vascular Function ◽

Vascular Dysfunction ◽

High Fat ◽

Enos Expression ◽

Unacylated Ghrelin ◽

Vascular Oxidative Stress ◽

Expression And Activity

Unacylated ghrelin (UnGhr) exerts several beneficial actions on vascular function. The aim of this study was to assess the effects of UnGhr on high-fat induced endothelial dysfunction and its underlying mechanisms. Thoracic aortas from transgenic mice, which were overexpressing UnGhr and being control fed either a standard control diet (CD) or a high-fat diet (HFD) for 16 weeks, were harvested and used for the assessment of vascular reactivity, endothelial nitric oxide synthase (eNOS) expression and activity, thiobarbituric acid reactive substances (TBARS) and glutathione levels, and aortic lipid accumulation by Oil Red O staining. Relaxations due to acetylcholine and to DEA-NONOate were reduced (p < 0.05) in the HFD control aortas compared to vessels from the CD animals. Overexpression of UnGhr prevented HFD-induced vascular dysfunction, while eNOS expression and activity were similar in all vessels. HFD-induced vascular oxidative stress was demonstrated by increased (p < 0.05) aortic TBARS and glutathione in wild type (Wt) mice; however, this was not seen in UnGhr mice. Moreover, increased (p < 0.05) HFD-induced lipid accumulation in vessels from Wt mice was prevented by UnGhr overexpression. In conclusion, chronic UnGhr overexpression results in improved vascular function and reduced plaque formation through decreased vascular oxidative stress, without affecting the eNOS pathway. This research may provide new insight into the mechanisms underlying the beneficial effects of UnGhr on the vascular dysfunction associated with obesity and the metabolic syndrome.

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Non-nutritive sweetener sucralose chronic consumption is able to reduce the deleterious effect of high-fat diet on body composition, glucose metabolism and vascular function in C57BL/6JR mice

Archives of Cardiovascular Diseases Supplements ◽

10.1016/j.acvdsp.2020.03.023 ◽

2020 ◽

Vol 12 (2-4) ◽

pp. 208

Author(s):

S. Risdon ◽

M. Paillargue ◽

G. Meyer ◽

G. Walther

Keyword(s):

Body Composition ◽

Glucose Metabolism ◽

High Fat Diet ◽

Vascular Function ◽

Deleterious Effect ◽

High Fat

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Impaired vascular function in small resistance arteries of LOX-1 overexpressing mice on high-fat diet

Cardiovascular Research ◽

10.1093/cvr/cvp089 ◽

2009 ◽

Vol 82 (3) ◽

pp. 493-502 ◽

Cited By ~ 26

Author(s):

Birgit Eichhorn ◽

Gregor Muller ◽

Anja Leuner ◽

Tatsuya Sawamura ◽

Ursula Ravens ◽

...

Keyword(s):

High Fat Diet ◽

Vascular Function ◽

Resistance Arteries ◽

High Fat ◽

Small Resistance

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High-Fat Diet in the Absence of Obesity Does Not Aggravate Surgically Induced Lymphoedema in Mice

European Surgical Research ◽

10.1159/000461579 ◽

2017 ◽

Vol 58 (3-4) ◽

pp. 180-192 ◽

Cited By ~ 5

Author(s):

Epameinondas Gousopoulos ◽

Sinem Karaman ◽

Steven T. Proulx ◽

Kristin Leu ◽

Dorina Buschle ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Vascular Function ◽

Lymphatic Vessel ◽

Immune Cell ◽

Control Group ◽

High Fat ◽

Lymphatic Vasculature ◽

Morphological Differences ◽

Surgically Induced

Background: Lymphoedema represents the cardinal manifestation of lymphatic dysfunction and is associated with expansion of the adipose tissue in the affected limb. In mice, high-fat diet (HFD)-induced obesity was associated with impaired collecting lymphatic vessel function, and adiposity aggravated surgery-induced lymphoedema in a mouse model. The aim of the current study was to investigate whether adiposity is necessary to impair lymphatic function or whether increased lipid exposure alone might be sufficient in a surgical lymphoedema model. Methods: To investigate the role of increased lipid exposure in lymphoedema development we used a well-established mouse tail lymphoedema model. Female mice were subjected to a short-term (6 weeks) HFD, without development of obesity, before surgical induction of lymphedema. Lymphoedema was followed over a period of 6 weeks measuring oedema, evaluating tissue histology and lymphatic vascular function. Results: HFD increased baseline angiogenesis and average lymphatic vessel size in comparison to the chow control group. Upon induction of lymphedema, HFD-treated mice did not exhibit aggravated oedema and no morphological differences were observed in the blood and lymphatic vasculature. Importantly, the levels of fibro-adipose tissue deposition were comparable between the 2 groups and lymphatic vessel function was not impaired as a result of the HFD. Although the net immune cell infiltration was comparable, the HFD group displayed an increased infiltration of macrophages, which exhibited an M2 polarization phenotype. Conclusions: These results indicate that increased adiposity rather than dietary influences determines predisposition to or severity of lymphedema.

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Consuming a balanced high fat diet for 16 weeks improves body composition, inflammation and vascular function parameters in obese premenopausal women

Metabolism ◽

10.1016/j.metabol.2014.01.004 ◽

2014 ◽

Vol 63 (4) ◽

pp. 562-573 ◽

Cited By ~ 16

Author(s):

Heidi J. Silver ◽

Hakmook Kang ◽

Charles D. Keil ◽

James A. Muldowney ◽

Heidi Kocalis ◽

...

Keyword(s):

Body Composition ◽

High Fat Diet ◽

Vascular Function ◽

Premenopausal Women ◽

High Fat

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AT2R stimulation with C21 prevents arterial stiffening and endothelial dysfunction in the abdominal aorta from mice fed a high-fat diet

Clinical Science ◽

10.1042/cs20210971 ◽

2021 ◽

Author(s):

Raquel González-Blázquez ◽

Martín Alcalá ◽

José Miguel Cárdenas ◽

Marta Viana ◽

Ulrike Muscha Steckelings ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Abdominal Aorta ◽

High Fat Diet ◽

Vascular Function ◽

Collagen Deposition ◽

High Fat ◽

Ecm Remodeling ◽

Diet Induced Obesity ◽

Compound 21

The aim of this study was to evaluate the effect of Compound 21 (C21), a selective AT2R agonist, on the prevention of endothelial dysfunction, extracellular matrix (ECM) remodeling and arterial stiffness associated with diet-induced obesity (DIO).  5-week-old male C57BL/6J mice were fed a standard (Chow) or high-fat diet (HF) for 6 weeks. Half of the animals of each group were simultaneously treated with C21 (1mg/kg/day, in the drinking water), generating 4 groups: Chow C, Chow C21, HF C, HF C21. Vascular function and mechanical properties were determined in the abdominal aorta. To evaluate ECM remodeling, collagen deposition, activity of metalloproteinases (MMP) 2 and 9 and TGF-b1 concentration were analyzed in the plasma. Abdominal aortas from HF C mice showed endothelial dysfunction as well as enhanced contractile but reduced relaxant responses to Ang II. This effect was abrogated with C21 treatment by preserving NO availability. A left-shift in the tension-stretch relationship, paralleled by an augmented β-index (marker of intrinsic arterial stiffness), and enhanced collagen deposition and MMP-2/-9 activities were also detected in HF mice. However, when treated with C21, HF mice exhibited lower TGF-b1 levels in abdominal aortas together with reduced MMP activities and collagen deposition compared with HF C mice.</p>  In conclusion, these data demonstrate that AT2R stimulation by C21 in obesity preserves NO availability and prevents unhealthy vascular remodeling, thus protecting the abdominal aorta in HF mice against the development of endothelial dysfunction, ECM remodeling and arterial stiffness.

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Interscapular and Perivascular Brown Adipose Tissue Respond Differently to a Short-Term High-Fat Diet

10.20944/preprints201902.0201.v1 ◽

2019 ◽

Cited By ~ 2

Author(s):

Peter Aldiss ◽

Jo Lewis ◽

David Boocock ◽

Amanda Miles ◽

Ian Bloor ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

Vascular Function ◽

Rna Degradation ◽

Whole Body ◽

Anatomical Location ◽

High Fat ◽

Short Term ◽

Brown Adipose

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n = 12) were fed either a standard (10% fat, n = 6) or high fat diet (HFD: 45% fat, n = 6) for 72 h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72 h induced rapid weight gain (c. 2.6%) and reduced serum NEFA with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and PPAR signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.

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Interscapular and Perivascular Brown Adipose Tissue Respond Differently to a Short-Term High-Fat Diet

Nutrients ◽

10.3390/nu11051065 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1065 ◽

Cited By ~ 4

Author(s):

Peter Aldiss ◽

Jo E. Lewis ◽

David J. Boocock ◽

Amanda K. Miles ◽

Ian Bloor ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

Vascular Function ◽

Rna Degradation ◽

Whole Body ◽

Anatomical Location ◽

High Fat ◽

Short Term ◽

Brown Adipose

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n=12) were fed either a standard (10% fat, n=6) or high fat diet (HFD: 45% fat, n=6) for 72h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72h induced rapid weight gain (c. 2.6%) and reduced serum non-esterified fatty acids (NEFA) with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and peroxisome proliferator-activated receptor (PPAR) signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g., Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.

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