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Detection of nutrients
and metabolic signals in the liver and gastrointestinal tract for the
control of food intake
Evidence suggests
that nutrients in the gastrointestinal tract and metabolic signals from the liver are
detected by vagal afferent fibers that provide input to the brain for
the control of food intake and the regulation of energy balance. By
using electrophysiological techniques to record the responses of single
visceral afferent nerve fibers the specific properties of these neurons can
be determined. Nutrients stimulate mucosal cells of the GI tract that
release paracrine subtances, such as serotonin, that act to stimulate
vagal afferent fibers that communicate to the brain.
Detection of toxins in
the stomach and intestine and its impact on nausea and
appetite
Many medications
produce nausea and vomiting, which in turn leads to loss of appetite and
reduced food intake, and can negatively affect recovery from disease.
Nausea and vomiting are frequently observed with use of cytotoxic
chemotherapy agents, but little is known about the neural pathways and
mechanism for detecting toxins. Gastrointestinal (GI) sensory nerve
fibers play an important role in the initiation of vomiting, and may
also be involved in the stimulation of nausea. My work focuses on
identifying the pathways and neurochemistry of GI vagal and spinal
afferent fibers and brain nuclei that are activated by toxins. An
understanding of the physiology of toxin detection may contribute to
nausea treatment in a large number of clinical situations, including
cancer chemotherapy, diabetic gastroparesis, anorexia nervosa, ischemic
gastropathy, chronic intestinal obstruction, abdominal malignancy, and
functional dyspepsia. Effective treatment of nausea may substantially
improve the quality of life for patients with chronic disease.
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Recording of four nerve filaments from a
gastrointestinal nerve (vagus) of the rat, each
contains the activity, action potentials, of many single neurons.
Click
here to see a
video of gastrointestinal nerve activity.
Note the increase in activity produced by infusion of serotonin
into the blood supply of the intestine.
Serotonin, a neurotransmitter, is involved in signaling the
presence of nutrients and toxins in the intestine by activation of nerve
fibers.
The activity of single nerve fibers (circled
clusters of data points) from a gastrointestinal nerve (vagus) of the rat can be distinguished by using
statistical analyses (PC, principal component scores).
Click
here to see a video of how this type of data appears
in 3-dimensions. These additional
data are from a recording of neural activity in the brainstem of the rat.
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