A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice

• Published in: Experimental neurology 2018-08, Vol.306, p.149-157
• Main Authors: Cooper, Michael A., Menta, Blaise W., Perez-Sanchez, Consuelo, Jack, Megan M., Khan, Zair W., Ryals, Janelle M., Winter, Michelle, Wright, Douglas E.
• Format: Article
• Language: English
• Subjects: Adiposity; Animals; Axons - pathology; Blood Glucose - metabolism; Diabetes; Diet, High-Fat; Diet, Ketogenic; DRG; Exercise; High-fat; Hyperalgesia - diet therapy; Hyperalgesia - etiology; Insulin - blood; Ketogenic; Ketones; Male; Metabolic Syndrome - complications; Metabolic Syndrome - diet therapy; Metabolic Syndrome - pathology; Mice; Mice, Inbred C57BL; Neurites; Pain; Peripheral Nerves - growth & development; Peripheral Nerves - pathology; Physical Conditioning, Animal; Weight Loss
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2018.05.011

Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice. High-fat-fed, exercised and ketogenic-fed mice had mildly elevated blood glucose; conversely, ketogenic diet-fed mice were unique in having reduced serum insulin levels. Ketogenic diet-fed mice never developed mechanical allodynia contrary to mice fed a high-fat diet. Ketogenic diet fed mice also had increased epidermal axon density compared all other groups. When a ketogenic diet was used as an intervention, a ketogenic diet was unable to reverse high-fat fed-induced metabolic changes but was able to significantly reverse a high-fat diet-induced mechanical allodynia. As an intervention, a ketogenic diet also increased epidermal axon density. In vitro studies revealed increased neurite outgrowth in sensory neurons from mice fed a ketogenic diet and in neurons from normal diet-fed mice given ketone bodies in the culture medium. These results suggest a ketogenic diet can prevent certain complications of prediabetes and provides significant benefits to peripheral axons and sensory dysfunction. •A ketogenic diet can reverse high-fat-induced mechanical allodynia.•Peripheral nerves are sensitive to metabolic change that may not mirror systemic metabolism.•A ketogenic diet and ketones stimulate sensory axon growth in vitro and in vivo.