Neuronal Inflammation is Associated with Changes in Epidermal Innervation in High Fat Fed Mice.

Area of Science:

• Neuroscience
• Metabolic Disorders
• Immunology

Background:

• Peripheral neuropathy (PN) is a diabetes complication linked to obesity and metabolic syndrome.
• High fat diets (HF) can induce diabetic PN signs in mice, but the underlying mechanisms are unclear.

Purpose of the Study:

• To investigate if neuronal inflammation is associated with mechanical hypersensitivity and nerve fiber changes in mice fed a high fat diet.
• To explore the pathogenesis of high fat diet-induced peripheral neuropathy.

Main Methods:

• Male C57Bl/6 mice were fed standard (Std) or high fat (HF) diets for 2, 4, or 8 weeks.
• Inflammatory mediators in dorsal root ganglia were quantified.
• Hindpaw mechanical sensitivity, intraepidermal nerve fiber density (IENFD), and TrkA nerve fiber density were assessed.

Main Results:

• HF diet increased body mass, blood glucose, and insulin levels compared to Std diet after 8 weeks.
• Elevated inflammatory mediators (IL-1α, RANTES, IL-5) were observed in HF-fed mice at earlier time points (2-4 weeks).
• Increased IENFD and TrkA fiber density were noted in HF mice after 4 weeks, but mechanical sensitivity remained unchanged.

Conclusions:

• Increased inflammatory mediators and cutaneous nerve fiber density in high fat-fed mice precede and accompany each other.
• High fat diets may promote neuronal inflammation and increase nociceptive nerve fiber density.
• Significant mechanical allodynia was not observed, indicating a complex relationship between diet-induced inflammation and pain.