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Understanding the Initiation and Progression of Diet-Induced Obesity and Associated Pathophysiology: Lessons Learned from a Rat Model

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Pathophysiology of Obesity-Induced Health Complications

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 19))

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Abstract

In human populations, the development and progression of obesity and its consequences on host systems is complex. Risk for obesity can reside in an individual’s genome, in epigenetic modifications, and in dietary and activity level variables. In addition to host system factors, the diet can also influence the gut microbiota leading to alterations to the host and such alterations can contribute to pathophysiological sequelae in the host. In order to better understand the impact of diet on obesity development, our group has studied the consequences of a high-fat/high-sucrose (HFS) diet on physiological systems of Sprague-Dawley male rats over short term and long term exposure to the diet. Medium (12 weeks) to long term (28 weeks) exposure to the diet leads to development of knee, shoulder, and to a lesser degree, hip damage, alterations to some skeletal muscles, development of insulin resistance and type 2 diabetes, development of features of systemic metabolic syndrome, fatty liver disease, and alterations to the vitreous humor of the eye. Very short time exposure (days to 4 weeks) leads to early, but fluctuating changes to serum cytokine profiles, changes to some skeletal muscles, and the onset of knee joint damage. Alterations to the gut microbiota are evident following medium to longer term exposure to the diet, but not during the shorter time frame. Exposure of rats on the HFS diet to either a modest exercise protocol or an oligofructose prebiotic initiated at the same time as the HFS diet is initiated, completely prevented development of joint damage at 12 weeks. Thus, the development of obesity, and at least some of its pathophysiological sequelae in this model, are modifiable by low cost, minimally invasive interventions. Such findings provide an opportunity to determine whether some of the consequences of exposure to the HFS diet develop in parallel or serially, and to identify potential points in the process that are reversible. Current studies are focused on addressing such questions.

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Acknowledgements

The authors thank Ruth Seerattan for excellent technical support for the studies. The authors acknowledge the financial support from the AHS Strategic Clinical Network Program (DAH), CIHR (WH & RAR), the CAPES fund of Brazil (JLR), and NIH T32 NIDDK, Alberta Innovates Health Solutions, Canadian Institutes of Health Research, Killam Trusts (KHC).

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Authors and Affiliations

  1. Human Performance Laboratory, Faculty of Kinesiology, c/o McCaig Institute for Bone & Joint Health, University of Calgary, 3330 Hospital Drive NW, T2N 4N1, Calgary, AB, Canada

    David A. Hart, Walter Herzog, Jaqueline L. Rios & Raylene A. Reimer

  2. Department of Surgery, McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada

    David A. Hart & Walter Herzog

  3. Bone & Joint Health Strategic Clinical Network, Alberta Health Services, Edmonton, AB, Canada

    David A. Hart

  4. Department of Biochemistry& Molecular Biology, University of Calgary, Calgary, AB, Canada

    Raylene A. Reimer

  5. Department of Orthopaedic Surgery, Washington University at St. Louis, St. Louis, MO, USA

    Kelsey H. Collins

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  1. David A. Hart
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  2. Walter Herzog
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  3. Jaqueline L. Rios
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  4. Raylene A. Reimer
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  5. Kelsey H. Collins
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Correspondence to David A. Hart .

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Editors and Affiliations

  1. Asper Clinical Research Institute and Office of Clinical Research, St. Boniface Hospital, Winnipeg, MB, Canada

    Paramjit S. Tappia

  2. Asper Clinical Research Institute and Office of Clinical Research, St. Boniface Hospital, Winnipeg, MB, Canada

    Bram Ramjiawan

  3. Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada

    Naranjan S. Dhalla

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Hart, D.A., Herzog, W., Rios, J.L., Reimer, R.A., Collins, K.H. (2020). Understanding the Initiation and Progression of Diet-Induced Obesity and Associated Pathophysiology: Lessons Learned from a Rat Model. In: Tappia, P., Ramjiawan, B., Dhalla, N. (eds) Pathophysiology of Obesity-Induced Health Complications. Advances in Biochemistry in Health and Disease, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-35358-2_7

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