Abstract
Background and Aims:
Diet-induced obesity (DIO) is an excellent model for examining human obesity comprising both genotypic and environmental (diet) factors. Decreased responsiveness to peripheral satiety signaling may be responsible for the hyperphagia in this model. In this study, we investigated responses to nutrient-induced satiation in outbred DIO and DIO-resistant (DR) rats fed a high-energy/high-fat (HE/HF) diet as well as intestinal satiety peptide content, intestinal nutrient-responsive receptor abundance and vagal anorectic receptor expression.
Methods:
Outbred DIO and DR rats fed a HE/HF diet were tested for short-term feeding responses following nutrient (glucose and intralipid (IL)) gastric loads. Gene and protein expressions of intestinal satiety peptides and fatty acid-responsive receptors were examined from isolated proximal intestinal epithelial cells and cholecystokinin-1 receptor (CCK-1R) and leptin receptor (LepR) mRNA from the nodose ganglia of DIO and DR animals.
Results:
DIO rats were less responsive to IL- (P<0.05) but not glucose-induced suppression of food intake compared with DR rats. DIO rats exhibited decreased CCK, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1; P<0.05 for each) protein expression compared with DR rats. Also, DIO rats expressed more G-protein-coupled receptor 40 (GPR40; P<0.0001), GPR41 (P<0.001) and GPR120 (P<0.01) relative to DR rats. Finally, there were no differences in mRNA expression for CCK-1R and LepR in the nodose ganglia of DIO and DR rats.
Conclusions:
Development of DIO may be partly due to decreased fat-induced satiation through low levels of endogenous satiety peptides, and changes in intestinal nutrient receptors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Archer ZA, Mercer JG . Brain responses to obesogenic diets and diet-induced obesity. Proc Nutr Soc 2007; 66: 124–130.
Levin BE . Sympathetic activity, age, sucrose preference, and diet-induced obesity. Obes Res 1993; 1: 281–287.
Bouret SG, Gorski JN, Patterson CM, Chen S, Levin BE, Simerly RB . Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab 2008; 7: 179–185.
Shin AC, Townsend RL, Patterson LM, Berthoud HR . ‘Liking’ and ‘wanting’ of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition. Am J Physiol Regul Integr Comp Physiol 2011; 301: R1267–R1280.
Hyland NP, Rybicka JM, Ho W, Pittman QJ, Macnaughton WK, Sharkey KA . Adaptation of intestinal secretomotor function and nutrient absorption in response to diet-induced obesity. Neurogastroenterol Motil 2010; 22: 602-e171.
Greenberg D, McCaffery J, Potack JZ, Bray GA, York DA . Differential satiating effects of fats in the small intestine of obesity-resistant and obesity-prone rats. Physiol Behav 1999; 66: 621–626.
De Jonghe BC, Hajnal A, Covasa M . Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats. Am J Physiol Regul Integr Comp Physiol 2005; 288: R292–R300.
Brenner L, Yox DP, Ritter RC . Suppression of sham feeding by intraintestinal nutrients is not correlated with plasma cholecystokinin elevation. Am J Physiol 1993; 264: R972–R976.
Little TJ, Feltrin KL, Horowitz M, Smout AJ, Rades T, Meyer JH et al. Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men. Am J Physiol Regul Integr Comp Physiol 2005; 289: R1090–R1098.
Little TJ, Feltrin KL, Horowitz M, Meyer JH, Wishart J, Chapman IM et al. A high-fat diet raises fasting plasma CCK but does not affect upper gut motility, PYY, and ghrelin, or energy intake during CCK-8 infusion in lean men. Am J Physiol Regul Integr Comp Physiol 2008; 294: R45–R51.
Williams DL, Hyvarinen N, Lilly N, Kay K, Dossat A, Parise E et al. Maintenance on a high-fat diet impairs the anorexic response to glucagon-like-peptide-1 receptor activation. Physiol Behav 2011; 103: 557–564.
le Roux CW, Batterham RL, Aylwin SJ, Patterson M, Borg CM, Wynne KJ et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 2006; 147: 3–8.
Covasa M, Ritter RC . Rats maintained on high-fat diets exhibit reduced satiety in response to CCK and bombesin. Peptides 1998; 19: 1407–1415.
Zwirska-Korczala K, Konturek SJ, Sodowski M, Wylezol M, Kuka D, Sowa P et al. Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. J Physiol Pharmacol 2007; 58 (Suppl 1): 13–35.
Verdich C, Toubro S, Buemann B, Lysgard Madsen J, Juul Holst J, Astrup A . The role of postprandial releases of insulin and incretin hormones in meal-induced satiety--effect of obesity and weight reduction. Int J Obes Relat Metab Disord 2001; 25: 1206–1214.
Feinle C, Chapman IM, Wishart J, Horowitz M . Plasma glucagon-like peptide-1 (GLP-1) responses to duodenal fat and glucose infusions in lean and obese men. Peptides 2002; 23: 1491–1495.
French SJ, Murray B, Rumsey RD, Sepple CP, Read NW . Preliminary studies on the gastrointestinal responses to fatty meals in obese people. Int J Obes Relat Metab Disord 1993; 17: 295–300.
le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006; 243: 108–114.
Swartz TD, Duca FA, Covasa M . Differential feeding behavior and neuronal responses to CCK in obesity-prone and -resistant rats. Brain Res 2010; 1308: 79–86.
Liou AP, Lu X, Sei Y, Zhao X, Pechhold S, Carrero RJ et al. The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 2011; 140: 903–912.
Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 2005; 11: 90–94.
Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA 2008; 105: 16767–16772.
Lan H, Hoos LM, Liu L, Tetzloff G, Hu W, Abbondanzo SJ et al. Lack of FFAR1/GPR40 does not protect mice from high-fat diet-induced metabolic disease. Diabetes 2008; 57: 2999–3006.
Tanaka T, Katsuma S, Adachi T, Koshimizu TA, Hirasawa A, Tsujimoto G . Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn Schmiedebergs Arch Pharmacol 2008; 377: 523–527.
Tazoe H, Otomo Y, Karaki S, Kato I, Fukami Y, Terasaki M et al. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res 2009; 30: 149–156.
Moran TH, Norgren R, Crosby RJ, McHugh PR . Central and peripheral vagal transport of cholecystokinin binding sites occurs in afferent fibers. Brain Res 1990; 526: 95–102.
Nefti W, Chaumontet C, Fromentin G, Tome D, Darcel N . A high-fat diet attenuates the central response to within-meal satiation signals and modifies the receptor expression of vagal afferents in mice. Am J Physiol Regul Integr Comp Physiol 2009; 296: R1681–R1686.
Donovan MJ, Paulino G, Raybould HE . CCK(1) receptor is essential for normal meal patterning in mice fed high fat diet. Physiol Behav 2007; 92: 969–974.
Lin S, Thomas TC, Storlien LH, Huang XF . Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int J Obes Relat Metab Disord 2000; 24: 639–646.
Schwartz GJ, Whitney A, Skoglund C, Castonguay TW, Moran TH . Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors. Am J Physiol 1999; 277: R1144–R1151.
Covasa M, Ritter RC . Reduced CCK-induced Fos expression in the hindbrain, nodose ganglia, and enteric neurons of rats lacking CCK-1 receptors. Brain Res 2005; 1051: 155–163.
Chomczynski P, Sacchi N . The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc 2006; 1: 581–585.
Covasa M, Ritter RC . Reduced sensitivity to the satiation effect of intestinal oleate in rats adapted to high-fat diet. Am J Physiol 1999; 277: R279–R285.
Brenner LA, Ritter RC . Type A CCK receptors mediate satiety effects of intestinal nutrients. Pharmacol Biochem Behav 1996; 54: 625–631.
Chandler PC, Wauford PK, Oswald KD, Maldonado CR, Hagan MM . Change in CCK-8 response after diet-induced obesity and MC3/4-receptor blockade. Peptides 2004; 25: 299–306.
Ritter RC . Gastrointestinal mechanisms of satiation for food. Physiol Behav 2004; 81: 249–273.
Li J, Ma W, Wang S . Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations. Regul Pept 2011; 171: 53–57.
Neary MT, Batterham RL . Gut hormones: implications for the treatment of obesity. Pharmacol Ther 2009; 124: 44–56.
Eissele R, Goke R, Willemer S, Harthus HP, Vermeer H, Arnold R et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 1992; 22: 283–291.
Ballantyne GH . Peptide YY(1-36) and peptide YY(3-36): Part I. Distribution, release and actions. Obes Surg 2006; 16: 651–658.
Theodorakis MJ, Carlson O, Michopoulos S, Doyle ME, Juhaszova M, Petraki K et al. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab 2006; 290: E550–E559.
Clegg DJ, Benoit SC, Reed JA, Woods SC, Dunn-Meynell A, Levin BE . Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am J Physiol Regul Integr Comp Physiol 2005; 288: R981–R986.
Shang Q, Saumoy M, Holst JJ, Salen G, Xu G . Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1. Am J Physiol Gastrointest Liver Physiol 2010; 298: G419–G424.
Boey D, Lin S, Karl T, Baldock P, Lee N, Enriquez R et al. Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity. Diabetologia 2006; 49: 1360–1370.
Williams DL, Baskin DG, Schwartz MW . Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety. Endocrinology 2009; 150: 1680–1687.
Yox DP, Brenner L, Ritter RC . CCK-receptor antagonists attenuate suppression of sham feeding by intestinal nutrients. Am J Physiol 1992; 262: R554–R561.
Cani PD, Dewever C, Delzenne NM . Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Br J Nutr 2004; 92: 521–526.
de Krom M, van der Schouw YT, Hendriks J, Ophoff RA, van Gils CH, Stolk RP et al. Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns. Diabetes 2007; 56: 276–280.
Covasa M . Deficits in gastrointestinal responses controlling food intake and body weight. Am J Physiol Regul Integr Comp Physiol 2010; 299: R1423–R1439.
Paulino G, Barbier de la Serre C, Knotts TA, Oort PJ, Newman JW, Adams SH et al. Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats. Am J Physiol Endocrinol Metab 2009; 296: E898–E903.
Broberger C, Holmberg K, Shi TJ, Dockray G, Hokfelt T . Expression and regulation of cholecystokinin and cholecystokinin receptors in rat nodose and dorsal root ganglia. Brain Res 2001; 903: 128–140.
Daly DM, Park SJ, Valinsky WC, Beyak MJ . Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse. J Physiol 2011; 589: 2857–2870.
Takiguchi S, Takata Y, Funakoshi A, Miyasaka K, Kataoka K, Fujimura Y et al. Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats. Gene 1997; 197: 169–175.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–546.
Peters JH, Karpiel AB, Ritter RC, Simasko SM . Cooperative activation of cultured vagal afferent neurons by leptin and cholecystokinin. Endocrinology 2004; 145: 3652–3657.
Matson CA, Reid DF, Cannon TA, Ritter RC . Cholecystokinin and leptin act synergistically to reduce body weight. Am J Physiol Regul Integr Comp Physiol 2000; 278: R882–R890.
de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE . Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 2011; 301: E187–E195.
Acknowledgements
We thank Muriel Thomas, Marie-Louise Noordine and Leila Ben Yahia for their assistance with the collection of intestinal epithelial cells and Tomas de Wouters for his assistance with qRT-PCR experiments.
Authors Contributions
FAD, TDS and MC were responsible for study concept and design. FAD, TDSYS and MC were responsible for acquisition of data. FAD and TDS were responsible for statistical analysis. FAD, TDS and MC were responsible for interpretation of the data, drafting of the manuscript and critical revisions for important intellectual content.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Duca, F., Swartz, T., Sakar, Y. et al. Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors. Int J Obes 37, 375–381 (2013). https://doi.org/10.1038/ijo.2012.45
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2012.45
Keywords
This article is cited by
-
Oligofructose improves small intestinal lipid-sensing mechanisms via alterations to the small intestinal microbiota
Microbiome (2023)
-
The metabolic impact of small intestinal nutrient sensing
Nature Communications (2021)
-
Lipid stimulation of fatty acid sensors in the human duodenum: relationship with gastrointestinal hormones, BMI and diet
International Journal of Obesity (2017)
-
Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats
Scientific Reports (2016)
-
Ileal brake activation: macronutrient-specific effects on eating behavior?
International Journal of Obesity (2015)