Adaptation of intestinal secretomotor function and nutrient absorption in response to diet-induced obesity.
BACKGROUND
The gut plays a significant role in the development of obesity, notably through peptide signaling to the brain. However, few studies have investigated intestinal function per se in a rodent model of diet-induced obesity (DIO). Our aim was to investigate intestinal secretomotor function and glucose transport in DIO and diet-resistant (DR) rat jejunum.


METHODS
Male outbred Sprague-Dawley rats were maintained on a medium high fat diet for 9-10 weeks and split into DIO and DR groups based on weight gain. Mucosal-submucosal preparations of the proximal jejunum were mounted in Ussing chambers and voltage-clamped at 0 mV. Glucose (10 mmol L(-1)), 2-deoxy-D-glucose (10 mmol L(-1)), and leptin (10 nmol L(-1)) were added to the luminal side of the tissue and veratridine (30 micromol L(-1)), bethanechol (100 micromol L(-1)), and forskolin (10 micromol L(-1)) were added to the basolateral side of the tissue.


RESULTS
Secretomotor responses were significantly decreased in DIO jejunum compared to DR tissues. Glucose-stimulated increases in I(sc) in DR animals, that were sensitive to leptin inhibition, were significantly reduced in DIO rats. Decreased sodium glucose transporter-1 mediated glucose transport was accompanied by a concomitant increase in the expression of jejunal glucose transporter-2.


CONCLUSIONS
These data suggest that submucosal nerve function is compromised in DIO rats and electrogenic glucose transport is significantly decreased. The latter may represent an adaptive response to limit nutrient absorption in the jejunum from DIO rats. However, the loss of secretomotor control may lead to an altered host defense with a resultant change in intestinal flora contributing to the maintenance of obesity.
Hyland
N P
NP
Hotchkiss Brain Institute, Snyder Institute of Infection, Immunity and Inflammation, and Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Rybicka
J M
JM
Ho
W
W
Pittman
Q J
QJ
Macnaughton
W K
WK
Sharkey
K A
KA
D000818:Animals; D015153:Blotting, Western; D004032:Diet; D005502:Food; D005769:Gastrointestinal Motility / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000502:physiology*; D007583:Jejunum / Q000502:physiology; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051246:Glucose Transport Proteins, Facilitative; D020738:Leptin; D005947:Glucose