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Models and Mechanisms of High-Fat Diet (HFD) Promotion of Pancreatic Cancer

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Murine Models, Energy Balance, and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 10))

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Abstract

There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. In this chapter, we discuss models and mechanisms of diet-induced obesity and pancreatic cancer development. The focus is on a state-of-the-art mouse model, the conditional KrasG12D mouse model. High-fat, high-calorie diet-fed animals showed early pancreatic neoplasia and important clinical features of human obesity, including weight gain and metabolic disturbances such as hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin-like growth factor (IGF-1). Consequently, the signal transduction pathways initiated by insulin/IGF-induced in pancreatic cancer cells, including the PI3K/Akt/mTORC1, are discussed. The high-fat, high-calorie diet-fed conditional KrasG12D mouse model will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemo-preventive strategies targeting obesity-associated pancreatic cancer development.

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Authors and Affiliations

  1. Department of Surgery, David Geffen School of Medicine at UCLA, 675 Charles E. Young Dr. South, MRL 2535, 90095, Los Angeles, CA, USA

    Hui-Hua Chang PhD

  2. Department of Surgery, David Geffen School of Medicine at UCLA, 10833 LeConte Avenue, 72-236 CHS, 90095, Los Angeles, CA, USA

    Guido Eibl MD

  3. Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, 900 Veterans Avenue, Warren Hall Room 11-124, 90095, Los Angeles, CA, USA

    Enrique Rozengurt DVM, PhD

  4. CURE: Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Guido Eibl MD & Enrique Rozengurt DVM, PhD

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  1. Hui-Hua Chang PhD
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  2. Guido Eibl MD
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  3. Enrique Rozengurt DVM, PhD
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Correspondence to Enrique Rozengurt DVM, PhD .

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  1. Center for Science, Health & Society, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

    Nathan A. Berger

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Chang, HH., Eibl, G., Rozengurt, E. (2015). Models and Mechanisms of High-Fat Diet (HFD) Promotion of Pancreatic Cancer. In: Berger, N. (eds) Murine Models, Energy Balance, and Cancer. Energy Balance and Cancer, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-319-16733-6_10

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