Does a high-fat/high-sucrose diet accelerate joint damage development when compared to a high-fat diet in a Wistar Han rat groove model of osteoarthritis?

Objectives Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2

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

Journal of Endocrinology ◽

10.1530/joe-15-0330 ◽

2015 ◽

Vol 228 (2) ◽

pp. 115-125 ◽

Cited By ~ 19

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.

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Prebiotic and Exercise Do Not Alter Knee Osteoarthritis in a Rat Model of Established Obesity

Cartilage ◽

10.1177/1947603520959399 ◽

2020 ◽

pp. 194760352095939

Author(s):

Jaqueline Lourdes Rios ◽

David A. Hart ◽

Raylene A. Reimer ◽

Walter Herzog

Keyword(s):

Risk Factor ◽

Knee Osteoarthritis ◽

Aerobic Exercise ◽

Joint Damage ◽

Metabolic Disturbance ◽

High Fat ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Prebiotic Fiber ◽

High Sucrose

Objective Metabolic disturbance is a known risk factor for cardiovascular disease and has been identified as a risk factor for the development of knee osteoarthritis. In this study, we sought to determine the effects of prebiotic fiber supplementation, aerobic exercise, and the combination of the 2 interventions, on the progression of knee osteoarthritis in a high-fat/high-sucrose diet-induced rat model of metabolic disturbance. Design Twelve-week-old male CD-Sprague-Dawley rats were either fed a standard chow diet, or a high-fat/high-sucrose diet. After 12 weeks on diets, rats consuming the high-fat/high-sucrose diet were randomized into 4 subgroups: a sedentary, an aerobic exercise, a prebiotic fiber supplementation, and an aerobic exercise combined with prebiotic fiber supplementation group. The aerobic exercise intervention consisted of a progressive treadmill training program for 12 weeks, while the prebiotic fiber was added to the high-fat/high-sucrose diet at a dose of 10% by weight for 12 weeks. Outcome measures included knee joint damage, body mass, percent body fat, bone mineral density, insulin sensitivity, and serum lipid profile. Results Aerobic exercise, or the combination of prebiotic fiber and aerobic exercise, improved select markers of metabolic disturbance, but not knee joint damage. However, these results need to be considered in view of the fact that the chow-fed rats had similar knee OA-like damage as the high-fat/high-sucrose–fed rats. Conclusion Exercise or prebiotics did not increase joint damage and might be good strategies for populations with metabolic knee osteoarthritis to alleviate other health-related problems, such as diabetes or cardiovascular disorders.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00113.2021 ◽

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.

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

PLoS ONE ◽

10.1371/journal.pone.0255997 ◽

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.

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