Pilot Studies to Demonstrate That Intestinal Mucosal Afferent Nerves Are Functionally Linked to Visceral Adipose Tissue

Abstract

Dietary capsaicin reduces rodent visceral fat weight. We tested the hypothesis that intact intestinal mucosal afferent nerve function is necessary for fat deposition in visceral adipose tissue sites. Rats were treated daily for 2 weeks with intragastric (chronic treatment) vehicle or capsaicin. Superior mesenteric artery blood flow and mesenteric and inguinal fat blood flow were measured before and after capsaicin was administered into the duodenum (acute treatment). Fat from all sites was dissected and weighed. Chronic capsaicin significantly attenuated acute capsaicin-induced mesenteric hyperemia but did not abolish the reflex wiping of the eye exposed to capsaicin, indicating that functional ablation was limited to the intestinal mucosal afferent nerves. The associated vasoconstriction in adipose tissue was inhibited at the visceral (mesenteric) site and maintained but attenuated at the subcutaneous (inguinal) site. The onset of vasoconstriction was instantaneous, indicating a reflex mechanism. There was a redistribution of fat from visceral to subcutaneous sites, reflected by a decrease and an increase in the percentage of body fat in the visceral and subcutaneous sites, respectively. These pilot studies reveal for the first time that normal intestinal mucosal afferent nerve function is necessary for the physiologic accumulation of fat in visceral adipose tissue sites.

Determination of Body Fat Distribution by Dual-Energy X-ray Absorptiometry and Attenuation of Visceral Fat Vasoconstriction by Enalapril

“…Stimulation of the mucosal afferent nerves in the gut produced peripheral vasoconstriction mediated by activation of the renin-angiotensin system [18]. Taken together, these reports and our data [1,19] suggest that the gut-related capsaicin-sensitive afferent nerves may play a role in integrating the signals from stimulation by fat nutrients in the gut lumen with preparation of the adipose tissue for storage of absorbed fat nutrients by way of the angiotensin II-mediated vasoconstrictive and lipogenic mechanisms.…”

“…Functional ablation of the intestinal mucosal capsaicinsensitive afferent nerves led to complete loss of this vasoconstriction in the visceral but not subcutaneous adipose tissue [1]. We hypothesize that the intestinal mucosal capsaicin-sensitive afferent nerves elicit events mediated in part by angiotensin II in adipose tissue (vasoconstriction) when nutrients are present in the intestinal lumen.…”

“…Capsaicin absorbed from the gut is almost completely metabolized before reaching the general circulation [15], excluding a direct effect of orally administered capsaicin on regional differences in adipose tissue responses. Functional ablation of afferent nerves after repeated daily intragastric capsaicin treatment for 2 weeks was limited to the gut mucosa [1] and was accompanied by a significant decrease in the proportion of total body fat in the visceral sites and a significant increase in the proportion of total body fat in the subcutaneous sites [1].…”

“…Disruption of intestinal mucosal afferent nerve function by intragastric capsaicin treatment redistributes fat from visceral to subcutaneous sites in obese experimental animals [1]. This is linked to attenuation of visceral fat vasoconstriction induced by stimulation of the intestinal mucosal afferent nerves.…”

Treating Diet-Induced Obesity: A New Role for Vagal Afferents?

“…As noted by Stearns et al [8], intestinal mucosal afferent nerves may influence the formation of visceral adipose tissue [17], and therefore, if these nerves include vagal afferents, this would be a direct pathway they could utilize to promote abdominal obesity. Another route by which vagal afferents could facilitate food intake that might lead to weight gain and fat accumulation involves alterations to their control of vago-vagal GI reflexes.…”