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A Ketogenic Diet Prevents Abnormal Changes in Peripheral Nerve Function Caused By A High‐Fat Diet
Author(s) -
Cooper Michael,
Ryals Janelle,
Wright Doug
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.636.37
Subject(s) - ketogenic diet , endocrinology , medicine , allodynia , diabetes mellitus , hyperalgesia , epilepsy , receptor , psychiatry , nociception
Mice given ad libitum access to a diet with high‐fat (54% kcal from fat) content begin to display clinical symptoms of prediabetic patients, including obesity, hyperglycemia, and mechanical allodynia. The molecular changes that underlie changes induced by a high‐fat diet that lead to neuropathic symptoms have yet to be identified. Our work has shown that mice given access to a running wheel while on a high‐fat diet develop mechanical allodynia over the first 6 weeks, which is then rescued to baseline levels during weeks 6–12. The current study examined how a ‘ketogenic’ diet (~90% kcal from fat) may alter prediabetic clinical symptoms to better understand how fat processing may impact the development of pre and overt diabetes, as well as to better understand the mechanism through which exercise may provide its benefits on high‐fat induced mechanical allodynia. Contrary to mice on a high‐fat diet, ketogenic fed animals never developed mechanical allodynia, suggesting maladaptations to utilizing carbohydrates as a fuel source may be key in leading to mechanical allodynia. Sensory nerve conduction velocities were also examined and mice fed a high fat diet displayed faster sensory conduction velocities compared to ketogenic and control mice. Motor nerve conduction velocities were also significantly faster in high‐fat sedentary and exercise mice, but were not changed in mice fed a ketogenic diet. Ketogenic diet‐fed mice displayed increased body weight and hyperglycemia, mirroring levels seen in high‐fat fed mice given access to exercise. Analyses of fat mass by percent of total mass revealed that both ketogenic‐diet fed and exercised mice had lower fat mass compared to high‐fat sedentary mice. Intriguingly, ketogenic‐diet fed mice had elevations in peripheral nerve fiber density in the hind paw relative to both normal chow and high‐fat fed mice. Together, these results suggest that a ketogenic diet is able to correct many of the clinical symptoms of high‐fat fed prediabetic mice, and importantly, mirrors many changes that can be corrected by exercise in in high‐fat fed mice. Support or Funding Information This work was supported by the NIH grants P20GM1033418 and RO1NS43314 (D.E.W)