Vascular Effects of Disrupting Endothelial mTORC1 (Mechanistic Target of Rapamycin Complex 1) Signaling in Obesity

2021 ◽  
Author(s):  
John J. Reho ◽  
Deng-Fu Guo ◽  
Andreas M. Beyer ◽  
Lauren Wegman-Points ◽  
Gary L. Pierce ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Target Of Rapamycin ◽  
High Fat ◽  
Vascular Effects ◽  
Mechanistic Target Of Rapamycin ◽  
Mtorc1 Signaling ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

The mechanistic target of rapamycin complex 1 (mTORC1) signaling complex is emerging as a critical regulator of cardiovascular function with alterations in this pathway implicated in cardiovascular diseases. In this study, we utilized animal models and human tissues to examine the role of vascular mTORC1 signaling in the endothelial dysfunction associated with obesity. In mice, obesity induced by high fat/high sucrose diet feeding for ~2 months resulted in aortic endothelial dysfunction without appreciable changes in vascular mTORC1 signaling. On the other hand, chronic high fat diet feeding (45% or 60% kcal: ~9 months) in mice resulted in endothelial dysfunction associated with elevated vascular mTORC1 signaling. Endothelial cells and visceral adipose vessels isolated from obese humans display a trend toward elevated mTORC1 signaling. Surprisingly, genetic disruption of endothelial mTORC1 signaling through constitutive or tamoxifen inducible deletion of endothelial Raptor (critical subunit of mTORC1) did not prevent or rescue the endothelial dysfunction associated with high fat diet feeding in mice. Endothelial mTORC1 deficiency also failed to reverse the endothelial dysfunction evoked by a high fat/high sucrose diet in mice. Taken together, these data show increased vascular mTORC1 signaling in obesity, but this vascular mTORC1 activation appears not to be required for the development of endothelial impairment in obesity.

scholarly journals A free-choice high-fat, high-sucrose diet induces hyperphagia, obesity, and cardiovascular dysfunction in female cycling and pregnant rats

2019 ◽  
Vol 316 (5) ◽  
pp. R472-R485 ◽  
Author(s):  
Hijab Ahmed ◽  
Johanna L. Hannan ◽  
John W. Apolzan ◽  
Oluwatobiloba Osikoya ◽  
Spencer C. Cushen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Energy Intake ◽  
Free Choice ◽  
Maternal Obesity ◽  
High Fat ◽  
Pregnant Rats ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

The main objective of these studies was to characterize metabolic, body composition, and cardiovascular responses to a free-choice high-fat, high-sucrose diet in female cycling and pregnant rats. In the nonpregnant state, female Sprague-Dawley rats offered a 3-wk free-choice high-fat, high-sucrose diet had greater energy intake, adiposity, serum leptin, and triglyceride concentrations compared with rats fed with standard chow and developed glucose intolerance. In addition, choice-diet-fed rats had larger cardiac ventricular weights, smaller kidney and pancreas weights, and higher blood pressure than chow-fed rats, but they did not exhibit resistance artery endothelial dysfunction. When the free-choice diet continued throughout pregnancy, rats remained hyperphagic, hyperleptinemic, and obese. Choice pregnant rats exhibited uterine artery endothelial dysfunction and had smaller fetuses compared with chow pregnant rats. Pregnancy normalized mean arterial blood pressure and pancreas weights in choice rats. These studies are the first to provide a comprehensive evaluation of free-choice high-fat, high-sucrose diet on metabolic and cardiovascular functions in female rats, extending the previous studies in males to female cycling and pregnant rodents. Free-choice diet may provide a new model of preconceptual maternal obesity to study the role of increased energy intake, individual food components, and preexisting maternal obesity on maternal and offspring physiological responses during pregnancy and after birth.

Sesamin improves endothelial dysfunction in renovascular hypertensive rats fed with a high-fat, high-sucrose diet

2009 ◽  
Vol 620 (1-3) ◽  
pp. 84-89 ◽  
Author(s):  
Xiang Kong ◽  
Jie-ren Yang ◽  
Li-qun Guo ◽  
Ying Xiong ◽  
Xiang-qi Wu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
High Fat ◽  
Hypertensive Rats ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

Geranium oil ameliorates endothelial dysfunction in high fat high sucrose diet induced metabolic complications in rats

2015 ◽  
Vol 15 ◽  
pp. 284-293 ◽  
Author(s):  
Rahul P. Kshirsagar ◽  
Manikanta V. Kothamasu ◽  
Madhoosudan A. Patil ◽  
G. Bhanuprakash Reddy ◽  
B. Dinesh Kumar ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
High Fat ◽  
Metabolic Complications ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

scholarly journals Ghrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet

2015 ◽  
Vol 228 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Tetsuya Kouno ◽  
Nobuteru Akiyama ◽  
Takahito Ito ◽  
Tomohiko Okuda ◽  
Isamu Nanchi ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Acylated Ghrelin ◽  
High Fat ◽  
Obesity And Diabetes ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

Ghrelin is an appetite-stimulating hormone secreted from stomach. Since the discovery that acylation of the serine-3 residue by ghrelin O-acyltransferase (GOAT) is essential for exerting its functions, GOAT has been regarded as an therapeutic target for attenuating appetite, and thus for the treatment of obesity and diabetes. However, contrary to the expectations, GOAT-knockout (KO) mice have not shown meaningful body weight reduction, under high-fat diet. Here, in this study, we sought to determine whether GOAT has a role in body weight regulation and glucose metabolism with a focus on dietary sucrose, because macronutrient composition of diet is important for appetite regulation. We found that peripherally administered acylated-ghrelin, but not unacylated one, stimulated sucrose consumption in a two-bottle-drinking test. The role of acylated-ghrelin in sucrose preference was further supported by the finding that GOAT KO mice consumed less sucrose solution compared with WT littermates. Then, we investigated the effect of dietary composition of sucrose on food intake and body weight in GOAT KO and WT mice. As a result, when fed on high-fat diet, food intake and body weight were similar between GOAT KO and WT mice. However, when fed on high-fat, high-sucrose diet, GOAT KO mice showed significantly reduced food intake and marked resistance to obesity, leading to amelioration of glucose metabolism. These results suggest that blockade of acylated-ghrelin production offers therapeutic potential for obesity and metabolic disorders caused by overeating of palatable food.

scholarly journals Impact of controlled high-sucrose and high-fat diets on eosinophil recruitment and cytokine content in allergen-challenged mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255997
Author(s):  
Caroline M. Percopo ◽  
Morgan McCullough ◽  
Ajinkya R. Limkar ◽  
Kirk M. Druey ◽  
Helene F. Rosenberg
Keyword(s):  
High Fat Diet ◽  
Airway Resistance ◽  
Allergen Challenge ◽  
Wild Type ◽  
High Fat ◽  
High Sugar ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose ◽  
High Calorie

Despite an ongoing focus on the role of diet in health and disease, we have only a limited understanding of these concepts at the cellular and molecular levels. While obesity has been clearly recognized as contributing to metabolic syndrome and the pathogenesis of adult asthma, recent evidence has linked high sugar intake alone to an increased risk of developing asthma in childhood. In this study, we examined the impact of diet in a mouse model of allergic airways inflammation with a specific focus on eosinophils. As anticipated, male C57BL/6 mice gained weight on a high-calorie, high-fat diet. However, mice also gained weight on an isocaloric high-sucrose diet. Elevated levels of leptin were detected in the serum and airways of mice maintained on the high-fat, but not the high-sucrose diets. We found that diet alone had no impact on eosinophil numbers in the airways at baseline or their recruitment in response to allergen (Alternaria alternata) challenge in either wild-type or leptin-deficient ob/ob mice. However, both bronchoalveolar lavage fluid and eosinophils isolated from lung tissue of allergen-challenged mice exhibited profound diet-dependent differences in cytokine content. Similarly, while all wild-type mice responded to allergen challenge with significant increases in methacholine-dependent total airway resistance (Rrs), airway resistance in mice maintained on the isocaloric high-sucrose (but not the high-calorie/high-fat) diet significantly exceeded that of mice maintained on the basic diet. In summary, our findings revealed that mice maintained on an isocaloric high-sucrose diet responded to allergen challenge with significant changes in both BAL and eosinophil cytokine content together with significant increases in Rrs. These results provide a model for further exploration of the unique risks associated with a high-sugar diet and its impact on allergen-associated respiratory dysfunction.

scholarly journals A High Fat Diet, But Not a High Sucrose Diet, Prevents Pressure Overload Induced Cardiac Dysfunction and Hypertrophy

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Monika Katarzyna Duda ◽  
Karen M O’Shea ◽  
Tracy A McElfresh ◽  
Brian D Hoit ◽  
William C Stanley
Keyword(s):  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Pressure Overload ◽  
High Fat ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose
Sign in / Sign up

Export Citation Format

Share Document