High Fat Diet Alters Gastrointestinal Function and Results in Reduced Enteric Neuron Density

Obese patients suffer from cardiovascular, metabolic and gastrointestinal disorders, including constipation, proposed to result from high fat diet (HFD)-induced enteric neuron loss. However, these studies used high-fat purified diets, containing reduced amounts of fiber compared to non-purified diets, known to alter gut physiology and microbiome composition. Therefore, we evaluated the effect of purified HFD-induced obesity on enteric neuron density and gastrointestinal transit compared to its proper control diet, that is, a purified control diet.

Wild type mice were fed a standard chow diet, purified low fat diet (LFD) or HFD. Colonic transit was measured via glass bead expulsion following 12, 18, and 24 weeks of diet. Colonic muscularis externa was collected for immunofluorescent stainings of enteric neurons.

Starting from 18 weeks of HFD, a decline in enteric neuron number was observed compared to LFD. In addition, delayed colonic transit was observed in HFD-fed mice when compared to LFD-fed animals after 18 weeks of exposure.

Our study demonstrates that prolonged exposure to a HFD results in a reduced enteric neuron density and delayed colonic transit, and underscores the need to use a proper control diet when evaluating the impact of a HFD on gut physiology.