Abstract P186: Chemical And Mechanical Activation Of The Mechanosensor Piezo1 Alters Adipogenesis In Pvat Preadipocytes

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Cristian Javier Rendon Mora ◽  
Emma D Flood ◽  
Miguel Leonardo Chirivi Gonzales ◽  
Janice Thompson ◽  
Stephanie W Watts ◽  
...  
Keyword(s):  
Gene Network ◽  
Mechanical Strain ◽  
Anatomical Location ◽  
Perivascular Adipose Tissue ◽  
Sd Rats ◽  
Adipocyte Progenitors ◽  
The Media ◽  
Adipogenic Gene ◽  
Adipogenic Effect ◽  
Oil Red O

During hypertension, vascular remodeling allows the blood vessel to withstand high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel. In the perivascular adipose tissue (PVAT) there is evidence for fibrosis development during hypertension; but PVAT remodeling is poorly understood. In stem cells (i.e., adipocyte progenitors) from non-PVAT depots, mechanical forces affect adipogenesis' commitment and lipogenic stages. The mechanism involves PIEZO1, a mechanosensor that boosts the differentiation of preadipocytes towards osteogenic and fibroblastic lineages. However, PVAT's particular anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis during normotensive and hypertensive states. Our objective was to evaluate PIEZO1's role in the adipogenic potential of preadipocytes. We hypothesize that activation of PIEZO1 reduces Adipogenesis in PVAT preadipocytes. Aortic (APVAT) was collected from male SD rats at 10 weeks of age (n=15) to harvest preadipocytes by Liberase™ digestion. Nonselective cationic channel PIEZO1 activity was evaluated with Ca 2+ indicator Fluo-4AM. Piezo1 was reduced with siRNA. Preadipocytes were differentiated for 4 d in adipogenic media containing PIEZO1 agonist Yoda1 (CON=0; YODA1=10μM). Mechanical strain (MS) was applied with FlexCell System at 12%, half-sine at 1 Hz for 4 d (MS+; MS-). Adipogenesis was evaluated by quantification of adipogenic gene network expression using PCR; lipid accumulation using lipophilic stains (Bodipy, siRNA experiments) or Oil Red O (FlexCell experiments). Adipogenesis efficiency is reported as Adipocyte/Total cells as measured in the IncuCyte Live-Cell ® system. Yoda1 reduced adipogenesis by 33% compared with CON and as expected, increased cytoplasmic Ca 2+ . In si Piezo1 cells, the anti-adipogenic effect of Yoda1 was reversed. MS+ reduced adipogenesis efficiency (0.15±0.06) compared with MS- (0.22±0.1). These data demonstrate that Piezo1 activation in PVAT may be an adaptive or pathogenic mechanism by which adipocyte populations are reduced, thus minimizing their secretion of vasoactive adipokines, and enhancing the deleterious impact of hypertension on PVAT function.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Pteryxin: A coumarin in Peucedanum japonicum Thunb leaves exerts antiobesity activity through modulation of adipogenic gene network

Nutrition ◽  
2014 ◽  
Vol 30 (10) ◽  
pp. 1177-1184 ◽  
Author(s):  
Ruwani N. Nugara ◽  
Masashi Inafuku ◽  
Kensaku Takara ◽  
Hironori Iwasaki ◽  
Hirosuke Oku
Keyword(s):  
Gene Network ◽  
Adipogenic Gene

scholarly journals Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries

2019 ◽  
Author(s):  
Ruda Zorc-Pleskovič ◽  
Marjeta Zorc ◽  
Dušan Šuput ◽  
Aleksandra Milutinović
Keyword(s):  
Adipose Tissue ◽  
Coronary Arteries ◽  
Obstructive Coronary Artery Disease ◽  
Inflammatory Cells ◽  
Elastic Membrane ◽  
Inflammatory Infiltration ◽  
Perivascular Adipose Tissue ◽  
Tunica Media ◽  
External Elastic Membrane ◽  
The Media

Obstructive coronary artery disease (CAD) is characterized by inflammation within the atherosclerotic coronary arteries. Infiltration of inflammatory cells into muscular media can lead to remodeling and weakening of the arterial wall. We examined the relationship between inflammatory infiltration in perivascular adipose tissue (PVAT), state of the external elastic membrane, and the intensity of inflammatory infiltration in the tunica media of coronary arteries obtained by endarterectomy from symptomatic patients with diffuse CAD. We analyzed endarterectomy sequesters from 22 coronary arteries that contained the intima, media, a part of the adventitia, and PVAT in at least one part of the sequester. The coronary arteries were divided into two groups according to the presence or absence of inflammatory infiltration in PVAT. Staining with hematoxylin-eosin and by the Movat's method showed atherosclerotic changes in the intima and media. Immunohistochemistry (anti-leukocyte common antigen [LCA] antibody) was used for the detection of leukocytes. We found a significant positive correlation between inflammatory infiltration in PVAT and preservation of the external elastic membrane of coronary arteries. Furthermore, we found a significant negative correlation between inflammatory infiltration in PVAT and the intensity of inflammatory infiltration in the media. It seems that the integrity of the external elastic membrane and the proinflammatory properties of PVAT restrain inflammatory cells within PVAT. Both effects may prevent the migration of inflammatory cells into the media and delay the development of CAD.

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 ◽  
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.

Blood vessels and the endothelium

2010 ◽  
pp. 2593-2603
Author(s):  
Patrick Vallance ◽  
Keith Channon
Keyword(s):  
Blood Vessels ◽  
Vessel Wall ◽  
Single Layer ◽  
Vasa Vasorum ◽  
Blood Vessel Wall ◽  
Internal Elastic Lamina ◽  
Perivascular Adipose Tissue ◽  
The Media ◽  
Elastic Laminae ◽  
Elastic Lamina

The blood vessel wall consists of the intima, the media, and the adventitia. Not all vessels have each layer, and the layers vary in size and structure between vessels. (1) The intima is made up of a single layer of endothelial cells on a basement membrane, beneath which—depending on vessel size—there may be a layer of fibroelastic connective tissue and an internal elastic lamina that provides both structure and flexibility. Embedded in the intima are pericytes. (2) The media is made up of smooth muscle cells, elastic laminae and extracellular matrix. (3) The adventitia is the outermost part of the vessel, composed mainly of fibroelastic tissue but also containing nerves, small feeding blood vessels (the vasa vasorum), and lymph vessels. The adventitia is directly related to the surrounding perivascular adipose tissue....

scholarly journals Yin Yang 1 and Adipogenic Gene Network Expression in Longissimus Muscle of Beef Cattle in Response to nutritional Management

2013 ◽  
Vol 7 ◽  
pp. GRSB.S11783 ◽  
Author(s):  
Sonia J. Moisá ◽  
Daniel W. Shike ◽  
William T. Meteer ◽  
Duane Keisler ◽  
Dan B. Faulkner ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Gene Network ◽  
Nutritional Management ◽  
Longissimus Muscle ◽  
Yin Yang 1 ◽  
Yin Yang ◽  
Adipogenic Gene

scholarly journals Diversity of lipid mediators in human adipose tissue depots

2013 ◽  
Vol 304 (12) ◽  
pp. C1141-C1149 ◽  
Author(s):  
Joan Clària ◽  
Binh T. Nguyen ◽  
Arin L. Madenci ◽  
C. Keith Ozaki ◽  
Charles N. Serhan
Keyword(s):  
Adipose Tissue ◽  
Cell Metabolism ◽  
Human Adipose Tissue ◽  
Lipid Mediators ◽  
Anatomical Location ◽  
Fat Cell ◽  
Perivascular Adipose Tissue ◽  
Fat Depots ◽  
Fat Depot ◽  
Marked Deficit

Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The “classic” eicosanoids prostaglandin (PG) E2, PGD2, PGF2α, leukotriene (LT) B4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2αdiffered significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE2.In this tissue, proresolving mediators RvD2 and LXA4were identified in lower levels than the proinflammatory LTB4. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD.

scholarly journals Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance

2020 ◽  
Vol 21 (11) ◽  
pp. 3884
Author(s):  
Chieh Yu ◽  
Ian W. Peall ◽  
Son H. Pham ◽  
Rachel K. Okolicsanyi ◽  
Lyn R. Griffiths ◽  
...  
Keyword(s):  
Human Mesenchymal Stem Cell ◽  
Protein Marker ◽  
Lineage Differentiation ◽  
Stems Cells ◽  
Membrane Bound ◽  
Adipogenic Gene ◽  
Lineage Markers ◽  
Oil Red O Staining ◽  
Osteoblast Lineage ◽  
Oil Red O

Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound syndecans (SDCs) and glypicans (GPCs) mediate hMSC lineage differentiation and with syndecan-1 (SDC-1) reported in both adipogenesis and osteogenesis, these macromolecules are potential regulators of the osteo-adipogenic balance. Here, we disrupted the HSPG profile in primary hMSC cultures via temporal knockdown (KD) of SDC-1 using RNA interference (RNAi) in undifferentiated, osteogenic and adipogenic differentiated hMSCs. SDC-1 KD cultures were examined for osteogenic and adipogenic lineage markers along with changes in HSPG profile and common signalling pathways implicated in hMSC lineage fate. Undifferentiated hMSC SDC-1 KD cultures exhibited a pro-adipogenic phenotype with subsequent osteogenic differentiation demonstrating enhanced maturation of osteoblasts. In cultures where SDC-1 KD was performed following initiation of differentiation, increased adipogenic gene and protein marker expression along with increased Oil Red O staining identified enhanced adipogenesis, with impaired osteogenesis also observed in these cultures. These findings implicate SDC-1 as a facilitator of the hMSC osteo-adipogenic balance during early induction of lineage differentiation.

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