Abstract 59: Vascular Glucagon-like Peptide 1 (GLP-1) Signaling Is Reduced In Obesity-related Hypertension In Female Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Risa Kiernan ◽  
Dhandevi Persand ◽  
Nicole Maddie ◽  
Maria Alicia Carrillo-Sepulveda
Keyword(s):  
Weight Loss ◽  
Vascular Dysfunction ◽  
Serum Levels ◽  
Western Diet ◽  
Obese Group ◽  
Female Rats ◽  
Receptor Protein ◽  
Chow Diet ◽  
Protective Effects ◽  
Glucagon Like Peptide 1

Obesity is a major risk factor for hypertension. Obesity-related hypertension impacts more women than men, but the underlying mechanisms remain unclear. GLP-1, an incretin released after food intake, exerts vasculo-protective effects. Human studies have shown that GLP-1 levels are decreased in obese patients. We hypothesized that vascular GLP-1 signaling is reduced in obesity and weight loss rescues this signaling. Eight-week-old female Wistar rats were randomized into three groups: LEAN (n=9) received a chow diet (5% fat, 48.7% carbohydrate [3.2% sucrose], 24.1% protein) for 28 weeks, OBESE (n=7) received a Western diet (21% fat, 50% carbohydrate [34% sucrose], 20% protein) for 28 weeks, and reverse obese (rOBESE) (n=7) received a Western diet for 18 weeks followed by 12 weeks of chow diet. The OBESE group exhibited increased body weight (395.6 vs. 285.4g LEAN, p<0.0001) and body mass index (6.8 vs. 5.1kg/m 2 LEAN, p<0.01), while the rOBESE group lost weight (337.0 vs. 395.6g OBESE, p<0.01). Direct measurement of blood pressure (BP) using a pressure-volume catheter inserted in the carotid artery revealed increased systolic (142.8 vs. 117.2mmHg LEAN, p<0.001), diastolic (125.0 vs. 92.7mmHg LEAN, p<0.001), and mean arterial BP (130.9 vs. 107.9mmHg LEAN, p<0.001) in the OBESE group. The rOBESE group sustained elevated systolic BP (139.1 vs.117.2mmHg LEAN, p<0.05). Endothelium-dependent vasodilation studies assessed by wire myograph demonstrated that the OBESE group exhibited impaired response to acetylcholine (Emax: 82.7% vs. 97.9% LEAN, p<0.001). Similar vascular impairment was observed in the rOBESE group (EMax: 81.3% vs 97.9% LEAN, p<0.001). Strikingly, while decreased GLP-1 serum levels in the OBESE group (10.6 vs. 18.4pM/mL LEAN, p<0.05) returned to normal levels in the rOBESE group (19.4 vs.18.4pM/mL LEAN), GLP-1 receptor protein expression was reduced in both groups (24% decrease in OBESE, 52% decrease in rOBESE) as compared to LEAN. Our results support that GLP-1 signaling is implicated in obesity-related vascular dysfunction in females and weight loss does not guarantee recovery of protective GLP-1 signaling nor improvement of vasodilation. Conclusion: GLP-1 is a potential therapeutic target for obesity-related hypertension in females.

Abstract P240: Activation Of Toll-like Receptor 4 (tlr4) Signaling In Mesenteric Arteries During Obesity Is Not Reversed By Weight Loss

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Dhandevi Persand ◽  
Nicole Maddie ◽  
Maria Carrillo Alicia Sepulveda
Keyword(s):  
Weight Loss ◽  
The United States ◽  
Western Diet ◽  
Mesenteric Arteries ◽  
Obese Group ◽  
Female Rats ◽  
Chow Diet ◽  
Tlr4 Signaling ◽  
Standard Chow Diet ◽  
Induced Hypertension

Obesity in the United States is associated with overconsumption of the high fat and high carbohydrate western diet. It is a major risk factor for hypertension. The mechanisms by which obesity contributes to the development of hypertension remain unresolved. While obese women are three-fold more likely to develop hypertension than lean women, the majority of obesity-induced hypertension research has been conducted using male cohorts. Thus, there is an urgent need to investigate the pathophysiology of obesity-induced hypertension in women. A previous study from our lab demonstrated that endothelial dysfunction found in obese female rats is associated with TLR4 signaling activation in the aorta revealing an inflammatory state in a conduit artery during obesity. The goal of this present study is to investigate whether weight loss by reversal of western diet-induced obesity normalizes TLR4 signaling in conduit and resistance arteries. To address this question, eight-week-old female Wistar rats were randomized into three experimental groups: the Obese group (n=10) was fed a western diet (21% fat, 50% carbohydrate [34% sucrose], 20% protein) and the Lean group (n=10) was fed a standard chow diet (5% fat, 48.7% carbohydrate [3.2% sucrose], 24.1% protein) for 20 weeks. The weight loss group (n=10) was fed a western diet for 20 weeks and a standard chow diet for 8 weeks. While weight loss reduced BMI (0.65 ±0.03 vs.0.82 ±0.02 obese, p<0.01), systolic blood pressure consistently measured at 7pm by tail-cuff plethysmography remained elevated (139.83 ± 15.3 vs.150.06 ± 4.5, p=0.09). At the experimental endpoint, thoracic aortas and mesenteric arteries were obtained for molecular analysis of TLR4 signaling. As previously shown, aortic TLR4 signaling of the obese group was activated. Weight loss normalized TLR4 and MyD88 expression in thoracic aortas; however, expression of MyD88 remained increased in mesenteric arteries (2.8 fold increase, p<0.01, n=6). This suggests that persistent hypertension despite weight loss is associated with a failure of TLR4-MyD88 signaling to normalize in the resistance vessels.

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.

Effects of the daily administration of gonadotrophin-releasing hormone on the anterior pituitary gland of rats with restricted feeding

1992 ◽  
Vol 134 (2) ◽  
pp. 177-NP ◽  
Author(s):  
F. Kotsuji ◽  
K. Hosokawa ◽  
T. Tominaga
Keyword(s):  
Weight Loss ◽  
Weight Reduction ◽  
Anterior Pituitary ◽  
Serum Levels ◽  
Female Rats ◽  
Daily Administration ◽  
Pituitary Cells ◽  
Restricted Feeding ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

ABSTRACT To investigate the influence of weight reduction on pituitary function and its modulation by gonadotrophin-releasing hormone (GnRH), female rats were restricted to 10 g food/day for 60 days. GnRH (5 μg) or saline (0·2 ml) were administered daily between days 31 and 60 of the period of underfeeding. Underfeeding brought about a decrease in the pituitary gonadotrophin content, serum levels of gonadotrophins and oestradiol, and the number and size of both LH- and FSH-positive pituitary cells. The administration of GnRH to underfed rats produced an increase in the pituitary and serum gonadotrophin levels and the number and size of both LH- and FSH-positive pituitary cells. These observations suggest that underfeeding and/or weight loss diminish the number and activity of the pituitary gonadotrophs, and that daily administration of GnRH both increases the number of gonadotrophs and augments their activity. Journal of Endocrinology (1992) 134, 177–182

scholarly journals Liraglutide Preserves CD34 + Stem Cells from Dysfunction Induced by High Glucose Exposure

2021 ◽  
Author(s):  
Annalisa Sforza ◽  
Vera Vigorelli ◽  
Erica Rurali ◽  
Elisa Gambini ◽  
Martina Arici ◽  
...  
Keyword(s):  
High Glucose ◽  
Intracellular Signaling ◽  
Receptor Protein ◽  
Intracellular Camp ◽  
Protective Effects ◽  
Hematopoietic Stem ◽  
Akt Phosphorylation ◽  
Glucagon Like Peptide 1 ◽  
Signaling Activation ◽  
And Function

Abstract Background: Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34+ hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34+ HSPC function.Methods: In cord blood (CB)-derived CD34+ HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and by Western Blot respectively. CD34+ HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34+ HSPC were evaluated. Results: CD34+ HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation and CXCR4/SDF-1α axis activity from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9-39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects. Conclusion: We provided the first evidence that CD34+ HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients.

scholarly journals Naringenin Protects against Acute Pancreatitis in Two Experimental Models in Mice by NLRP3 and Nrf2/HO-1 Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Yong Li ◽  
Yiyuan Pan ◽  
Lin Gao ◽  
Jingzhu Zhang ◽  
Xiaochun Xie ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Mild Acute Pancreatitis

Background. Naringenin (Nar) is a type of flavonoid and has been shown to have anti-inflammatory and antioxidative properties. However, the effects of Nar on acute pancreatitis (AP) have not been well studied. In this study, we aimed to investigate the function of Nar in a mouse model of AP. Methods. Mild acute pancreatitis (MAP) was induced by caerulein (Cae), and severe acute pancreatitis (SAP) was induced by L-arginine in mice. Nar was administered intraperitoneally at doses of 25, 50, or 100 mg/kg following MAP induction and at a dose of 100 mg/kg following SAP induction. The serum levels of cytokines, lipase, and amylase were determined, and pancreatic and pulmonary tissues were harvested. Results. The serum levels of amylase, lipase, and cytokines were significantly decreased in both MAP and SAP models after Nar treatment. The malondialdehyde (MDA) levels of the pancreatic tissue was significantly reduced in both MAP and SAP after Nar treatment. In contrast, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl (T-SH), and non-proteinsulthydryl (NP-SH) were markedly increased in both MAP and SAP after Nar treatment. The injury in pancreatic and pulmonary tissues was markedly improved as evidenced by the inhibited expression of myeloperoxidase, nod-like receptor protein 3, and interleukin 1 beta as well as the enhanced expression of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in pancreatic tissues. Conclusions. Nar exerted protective effects on Cae-induced MAP and L-arginine-induced SAP in mice, suggesting that Nar may be a potential therapeutic intervention for AP.

Digestive n‐6 Lipid Oxidation, a Key Trigger of Vascular Dysfunction and Atherosclerosis in the Western Diet: Protective Effects of Apple Polyphenols

2021 ◽  
pp. 2000487
Author(s):  
Gaëtan Bolea ◽  
Clothilde Philouze ◽  
Mathilde Dubois ◽  
Sydney Risdon ◽  
Anaïs Humberclaude ◽  
...  
Keyword(s):  
Lipid Oxidation ◽  
Vascular Dysfunction ◽  
Western Diet ◽  
Protective Effects

scholarly journals Inhibition of Nitric Oxide Synthase by L-NAME Promotes Cisplatin-Induced Nephrotoxicity in Male Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fatemeh Moslemi ◽  
Mehdi Nematbakhsh ◽  
Fatemeh Eshraghi-Jazi ◽  
Ardeshir Talebi ◽  
Hamid Nasri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Weight Loss ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Group 2 ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Group 1

Objective. Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats. Methods. Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male, n=6 and group 2, female, n=6) received saline. Groups 3 (male, n=8) and 4 (female, n=8) were treated with L-NAME (4 mg/kg, i.p.), and groups 5 (male, n=8) and 6 (female, n=8) received CP (3 mg/kg) for 7 days. Groups 7 (male, n=8) and 8 (female, n=8) were treated with L-NAME and CP for 7 days. Results. The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats (P<0.05). CP alone increased kidney damage significantly (P<0.05 ), however, the damage induced by combination of CP and L-NAME was gender-related. Conclusion. NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related.

scholarly journals The investigation effect of weight loss on serum vaspin, apelin-13, and obestatin levels in obese individual

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Cansu Can Figen ◽  
Tevfik Noyan ◽  
Özlem Özdemir
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Body Weight ◽  
Serum Insulin ◽  
Serum Levels ◽  
Obese Individual ◽  
Obese Group ◽  
Elisa Method ◽  
Obese Subjects ◽  
Resistance Assessment

AbstractObjectivesIt was aimed to investigate if there were any significant corresponding changes on adipokine levels in obese subjects who achieved a 10% reduction in body weight.MethodsThirty obese and 25 healthy adults were enrolled in present study, and serum levels of vaspin, apelin-13, obestatin, and insulin were determined with the ELISA method.ResultsThe serum obestatin and apelin-13 values of the obese group obtained as basal and after weight loss was significantly lower than in controls (p<0.05, p<0.01, p<0.01, p<0.05, respectively); however, weight loss did not cause significant changes on these parameters in obese groups (p>0.05). The vaspin level did not differ between the groups (p>0.05). The obese group had characterized increased serum insulin and insulin resistance assessment by the homeostatic assay (HOMA-IR) levels compared to controls (p<0.01, p<0.05, respectively); also, weight loss caused a significant decrease in these parameters compared to basal levels (p<0.01). No significant correlation was detected among the vaspin, apelin-13 and obestatin levels in the obese group (p>0.05).ConclusionsObese individuals exhibited decreased levels of apelin-13 and obestatin. Moreover, 10% weight loss caused a significant reduction of insulin resistance, but no significant change was detected on apelin-13, obestatin, and vaspin levels.

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