High-Fat Diet Disrupt Nerve Function by Targeting Schwann Cells.

Area of Science:

• Neuroscience
• Metabolic Disorders
• Cell Biology

Background:

• Diabetic peripheral neuropathy (DPN) is a significant diabetes complication.
• Schwann cell dysfunction is increasingly recognized as a key factor in DPN progression.

Purpose of the Study:

• To investigate the impact of high-fat diet (HFD)-induced metabolic syndrome (MetS) on Schwann cells and peripheral nerve function.
• To examine sex-specific differences in HFD-induced neuropathy in mice.

Main Methods:

• Mice were fed standard or HFD for 33 weeks, with metabolic and nerve function assessments.
• Methods included nerve conduction velocities, behavioral tests, nerve fiber density counts, and sciatic nerve morphology.
• Myelin protein expression was analyzed using Western blotting and immunohistochemistry.

Main Results:

• HFD induced MetS features in both sexes, with males showing more severe hyperglycemia.
• HFD mice exhibited signs of DPN, including thermal hyperalgesia, reduced nerve fiber density, and slowed nerve conduction.
• Sex-specific myelin defects were observed, with males showing myelin thinning and increased PMP2, while females had myelin decompaction without strength deficits.

Conclusions:

• HFD-induced MetS impairs peripheral nerve health and Schwann cell function in a sex-dependent way.
• Myelin alterations and PMP2 upregulation suggest a role for lipid metabolism in neuropathy.
• Schwann cells are critical in MetS-associated neuropathy, necessitating sex-specific treatments.