Na_v1.8 neurons are involved in limiting acute phase responses to dietary fat

Highlights

• Peripheral afferents are dispensable to the regulation of energy balance.

• Mice lacking peripheral afferents are intolerant to high-fat diet.

• Saturated fat produces an exaggerated acute phase response in mice lacking peripheral afferents.

Abstract

Objective and methods

Metabolic viscera and their vasculature are richly innervated by peripheral sensory neurons. Here, we examined the metabolic and inflammatory profiles of mice with selective ablation of all Na_v1.8-expressing primary afferent neurons.

Results

While mice lacking sensory neurons displayed no differences in body weight, food intake, energy expenditure, or body composition compared to controls on chow diet, ablated mice developed an exaggerated inflammatory response to high-fat feeding characterized by bouts of weight loss, splenomegaly, elevated circulating interleukin-6 and hepatic serum amyloid A expression. This phenotype appeared to be directly mediated by the ingestion of saturated lipids.

Conclusions

These data demonstrate that the Na_v1.8-expressing afferent neurons are not essential for energy balance but are required for limiting the acute phase response caused by an obesogenic diet.