Abstract
Previous evidence indicates that duodenal lipid sensing engages gut-brain neurocircuits to determine food intake and hepatic glucose production, but a potential role for gut-brain communication in the control of energy expenditure remains to be determined. Here, we tested the hypothesis that duodenal lipid sensing activates a gut–brain–brown adipose tissue neuraxis to regulate thermogenesis. We demonstrate that direct administration of lipids into the duodenum increases brown fat temperature. Co-infusion of the local anesthetic tetracaine with duodenal lipids abolished the lipid-induced increase in brown fat temperature. Systemic administration of the CCKA receptor antagonist devazepide blocked the ability of duodenal lipids to increase brown fat thermogenesis. Parenchymal administration of the N-methyl-d-aspartate receptor blocker MK-801 directly into the caudomedial nucleus of the solitary tract also abolished duodenal lipid-induced activation of brown fat thermogenesis. These findings establish that duodenal lipid sensing activates a gut–brain–brown fat axis to determine brown fat temperature, and thereby reveal a previously unappreciated pathway that regulates thermogenesis.
Highlights
The energetic relevance of brown adipose tissue (BAT) thermogenesis in adult human physiology has recently found new support after the publication of three independent studies consistently demonstrating the presence of metabolically-active BAT in adult humans using tomography technologies [1,2,3]
Within the small intestinal mucosa, gut vagal afferent fibers are in close apposition to CCK immunoreactive endocrine cells [13], CCKA receptors are expressed on and transported in gut vagal afferents [14,15], and CCKA receptors mediate the anorexigenic effect of intestinal lipids [11]
Duodenal Lipid Sensing Increases BAT Temperature Intraduodenal saline infusion in overnight fasted rats minimally affected BAT temperature, which non-significantly decreased by 0.4760.24uC during the 2 h following the beginning of the infusion (Figure 1)
Summary
The energetic relevance of brown adipose tissue (BAT) thermogenesis in adult human physiology has recently found new support after the publication of three independent studies consistently demonstrating the presence of metabolically-active BAT in adult humans using tomography technologies [1,2,3]. Surgical or chemical destruction of vagal afferents block the feeding inhibitory effects of duodenal lipids and intraperitoneal CCK [16]. The feeding inhibitory actions of peripheral CCK are mediated by NMDA receptors in the caudomedial nucleus of the solitary tract (NTS), where gut vagal afferents terminate [17]. Duodenal fat infusion activates this gut-CCK -NTS glutamatergic pathway to limit nutrient availability by suppressing hepatic glucose production [18]. These data support a gut-brainstem axis critical in the negative feedback control of ingestion and glucose homeostasis following duodenal lipid infusions. A potential role for a gut-NTS-BAT axis in the control of thermogenesis in response to duodenal fat sensing remains unexplored. The purpose of these experiments was to identify the degree to which the gut-brain axis could be implicated in the thermogenic effects of gut nutrient infusions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
