Authors
James G. Burchfield
Melkam A. Kebede
Christopher C. Meoli
Jacqueline Stockli
P. T. Whitworth
Amanda L. Wright
Nolan Hoffman
Annabel Y. Minard
Xiuquan Ma
James R. Krycer
Marin E. Nelson
Shi-XIong Tan
Belinda Yau
Kristen C. Thomas
Natalie K. P. Wee
Ee-Cheng Khor
Ronaldo F. Enriquez
Bryce Vissel
Trevor J. Biden
Paul A. Baldock
Kyle L. Hoehn
James Cantley
Gregory J. Cooney
David E. James
Daniel J. Fazakerley
Publication Date
2018
Publication Details
Burchfield, J. G, Kebede, M. A, Meoli, C. C, Stockli, J., Whitworth, P. T, Wright, A. L, Hoffman, N., Minard, A. Y, Ma, X., Krycer, J. R, Nelson, M. E, Tan, S., Yau, B., Thomas, K. C, Wee, N. K, Khor, E., Enriquez, R. F, Vissel, B., Biden, T. J, Baldock, P. A, Hoehn, K. L, Cantley, J., Cooney, G. J, James, D. E & Fazakerley, DJ. (2018). High dietary fat and sucrose result in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. Journal of Biological Chemistry,293(15), L. Gierasch. 5731-5745.: American Society for Biochemistry and Molecular Biology, Inc.. Retrieved from https://doi.org/10.1074/jbc.RA117.000808
Abstract
Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegeneration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, here we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD). HFHSD-fed mice rapidly exhibited metabolic alterations, including obesity, hyperleptinemia, physical inactivity, glucose intolerance, peripheral insulin resistance, fasting hyperglycemia, ectopic lipid deposition, and bone deterioration. Prolonged exposure to HFHSD resulted in morbid obesity, ectopic triglyceride deposition in liver and muscle, extensive bone loss, sarcopenia, hyperinsulinemia, and impaired short-term memory. Although many of these defects are typically associated with aging, HFHSD did not alter telomere length in white blood cells, indicating that this diet did not generally promote all aspects of aging. Strikingly, glucose homeostasis was highly dynamic. Glucose intolerance was evident in HFHSD-fed mice after 1 week and was maintained for 24 weeks. Beyond 24 weeks, however, glucose tolerance improved in HFHSD-fed mice, and by 60 weeks, it was indistinguishable from that of chow-fed mice. This improvement coincided with adaptive β-cell hyperplasia and hyperinsulinemia, without changes in insulin sensitivity in muscle or adipose tissue. Assessment of insulin secretion in isolated islets revealed that leptin, which inhibited insulin secretion in the chow-fed mice, potentiated glucose-stimulated insulin secretion in the HFHSD-fed mice after 60 weeks. Overall, the excessive calorie intake was accompanied by deteriorating function of numerous physiological systems.
School/Institute
Mary MacKillop Institute for Health Research
Document Type
Journal Article
Access Rights
ERA Access