scholarly journals Conditioned preference for sweet stimuli in OLETF rat: effects of food deprivation

2007 ◽  
Vol 292 (5) ◽  
pp. R1819-R1827 ◽  
Author(s):  
Bart C. De Jonghe ◽  
Andras Hajnal ◽  
Mihai Covasa
Keyword(s):  
Food Deprivation ◽  
Receptor Expression ◽  
Sucrose Intake ◽  
Flavor Preference ◽  
Oletf Rats ◽  
Conditioned Preference ◽  
Outbred Strain ◽  
Long Evans ◽  
Oletf Rat ◽  
Conditioned Flavor

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an outbred strain of Long- Evans Tokushima Otsuka rat (LETO) that lacks CCK-1 receptor expression, is hyperphagic and develops obesity and type-2 diabetes. The present study sought to assess how OLETF rats alter intake, preference, and conditioned preference of palatable solutions after acute food deprivation. Our results show that after 24 h chow restriction, LETO rats increase both sucrose intake and two-bottle sucrose preference relative to their free-fed baseline, whereas OLETF rats do not increase sucrose intake (0.3 M or 1.0 M sucrose) or preference (1.0 M vs. 0.3 M sucrose) when they are food deprived. In contrast, OLETF rats exhibit a higher conditioned flavor preference when sucrose is used as unconditioned stimulus (US) relative to LETO rats, whether overnight food restricted (81% vs. 71% for OLETF and LETO rats, respectively) or free fed (82% vs. 54% for OLETF and LETO rats, respectively) during the test. When a noncaloric saccharin solution is used as US, OLETF rats show a higher preference for the saccharin-associated flavor relative to LETO rats when nondeprived (76% vs. 58% for OLETF and LETO rats, respectively); however, neither strain shows differential conditioned flavor preference for saccharin in the deprivation state during the test. These findings suggest that OLETF rats fail to integrate postabsorptive and orosensory effects of sucrose in a conditioning setting to influence intake. Thus, it appears that OLETF rats form preferences for sucrose based largely on orosensory and hedonic properties of the solution, rather than caloric value.

Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats

2005 ◽  
Vol 288 (1) ◽  
pp. R292-R300 ◽  
Author(s):  
Bart C. De Jonghe ◽  
Andras Hajnal ◽  
Mihai Covasa
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Taste Preference ◽  
Separate Experiment ◽  
Sucrose Intake ◽  
Oletf Rats ◽  
Oral Stimulation ◽  
Preference Functions ◽  
Long Evans

CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and develop obesity and Type 2 diabetes. In this strain, taste preference functions have not been investigated. Therefore, a series of short-access, two-bottle tests were performed in age-matched prediabetic OLETF and nonmutant Long-Evans Tokushima Otsuka (LETO) rats to investigate preference for sucrose (0.03, 0.1, 0.3, or 1.0 M) presented with a choice of water. To discern orosensory from postgastric factors that may contribute to this preference, in a separate experiment, rats were allowed to sham feed sucrose in the absence or presence of duodenal sucrose infusion (0.3, 0.6, or 1.0 M). In the two-bottle real-feeding tests, OLETF rats exhibited a greater preference for 0.3 M sucrose (91.2 ± 1.7 and 78.5 ± 3.4% for OLETF and LETO, respectively; P < 0.01) and 1.0 M sucrose (65.3 ± 1.2 and 57.5 ± 2.7% for OLETF and LETO, respectively; P < 0.05) than LETO rats. OLETF rats also sham fed less of the lowest (0.03 M; 33.8 ± 4.8 and 58.3 ± 7.3 ml for OLETF and LETO, respectively; P < 0.05) and more of the highest (1.0 M; 109.9 ± 6.5 and 81.0 ± 3.9 ml for OLETF and LETO, respectively; P < 0.01) concentration of sucrose relative to LETO rats. Finally, intraduodenal sucrose infusions (0.6 and 1.0 M) produced a smaller reduction of 0.3 M sham sucrose intake [14.1 ± 8.1 vs. 52.5 ± 3.3 ml and 49.4 ± 8.0 vs. 82.4 ± 3.2 ml for 0.6 M ( P < 0.01) and 1.0 M ( P < 0.05) infusions in OLETF and LETO, respectively]. These findings demonstrate that OLETF rats display an increased preference for sucrose, an effect that is at least partially influenced by the orosensory stimulating effect of sucrose. This enhanced responsiveness to oral stimulation, coupled with the deficit in responding to the postingestive feedback of intestinal sucrose, may contribute additively to the development of hyperphagia and weight gain in OLETF rats.

scholarly journals Altered Pontine Taste Processing in a Rat Model of Obesity

2008 ◽  
Vol 100 (4) ◽  
pp. 2145-2157 ◽  
Author(s):  
Peter Kovacs ◽  
Andras Hajnal
Keyword(s):  
Sucrose Concentration ◽  
Response Threshold ◽  
Response Functions ◽  
Unit Recording ◽  
Oletf Rats ◽  
Obese Rats ◽  
Prevalence Of Obesity ◽  
Long Evans ◽  
Taste Processing ◽  
Oletf Rat

The increased palatability of modern diet contributes to eating beyond homeostatic need and in turn to the growing prevalence of obesity. How palatability is coded in taste-evoked neural activity and whether this activity differs between obese and lean remains unknown. To investigate this, we used extracellular single-unit recording in the second central gustatory relay, the pontine parabrachial nucleus while stimulating the tongue with various concentrations of sucrose (0.01–1.5 M) in Otsuka Long Evans Tokushima Fatty (OLETF) rats, lacking CCK-1R. The analyses included a total of 179 taste-responsive neurons in age-matched prediabetic, obese OLETF and lean Long Evans Tokushima Otsuka (LETO) controls. Compared with LETO, we found more NaCl-, and fewer sucrose-responsive neurons (67 vs. 47% and 14 vs. 32%), and an overall reduced response magnitude to sucrose in the OLETF rats. Further, in the obese rats there was a rightward shift in sucrose concentration-response functions relative to lean controls with a higher response-threshold (0.37 ± 0.05 vs. 0.23 ± 0.2 M, P < 0.05) and maximal neural response to higher sucrose concentrations (0.96 ± 0.07 vs. 0.56 ± 0.5 M, P < 0.001). These findings demonstrate altered central gustatory processing for sucrose in obese OLETF rat and further support the notion that palatability is encoded in the across neuron pattern.

scholarly journals Daily exercise vs. caloric restriction for prevention of nonalcoholic fatty liver disease in the OLETF rat model

2011 ◽  
Vol 300 (5) ◽  
pp. G874-G883 ◽  
Author(s):  
R. Scott Rector ◽  
Grace M. Uptergrove ◽  
E. Matthew Morris ◽  
Sarah J. Borengasser ◽  
M. Harold Laughlin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Caloric Restriction ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Oletf Rats ◽  
Daily Exercise ◽  
Long Evans ◽  
Oletf Rat

The maintenance of normal body weight either through dietary modification or being habitually more physically active is associated with reduced incidence of nonalcoholic fatty liver disease (NAFLD). However, the means by which weight gain is prevented and potential mechanisms activated remain largely unstudied. Here, we sought to determine the effects of obesity prevention by daily exercise vs. caloric restriction on NAFLD in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. At 4 wk of age, male OLETF rats ( n = 7–8/group) were randomized to groups of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or caloric restriction (OLETF-CR; 70% of SED) until 40 wk of age. Nonhyperphagic, control strain Long-Evans Tokushima Otsuka (LETO) rats were kept in sedentary cage conditions for the duration of the study (LETO-SED). Both daily exercise and caloric restriction prevented obesity and the development of type 2 diabetes observed in the OLETF-SED rats, with glucose tolerance during a glucose tolerance test improved to a greater extent in the OLETF-EX animals (30–50% lower glucose and insulin areas under the curve, P < 0.05). Both daily exercise and caloric restriction also prevented excess hepatic triglyceride and diacylglycerol accumulation ( P < 0.001), hepatocyte ballooning and nuclear displacement, and the increased perivenular fibrosis and collagen deposition that occurred in the obese OLETF-SED animals. However, despite similar hepatic phenotypes, OLETF-EX rats also exhibited increased hepatic mitochondrial fatty acid oxidation, enhanced oxidative enzyme function and protein content, and further suppression of hepatic de novo lipogenesis proteins compared with OLETF-CR. Prevention of obesity by either daily exercise or caloric restriction attenuates NAFLD development in OLETF rats. However, daily exercise may offer additional health benefits on glucose homeostasis and hepatic mitochondrial function compared with restricted diet alone.

scholarly journals Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction

2012 ◽  
Vol 37 (6) ◽  
pp. 1054-1062 ◽  
Author(s):  
Justin A. Fletcher ◽  
Grace M. Meers ◽  
M. Harold Laughlin ◽  
Jamal A. Ibdah ◽  
John P. Thyfault ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Content ◽  
Fibroblast Growth Factor ◽  
Caloric Restriction ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Oletf Rats ◽  
Daily Exercise ◽  
Long Evans ◽  
Oletf Rat

Chronic treatment with fibroblast growth factor 21 (FGF-21) favorably improves obesity and nonalcoholic fatty liver disease (NAFLD) outcomes; however, FGF-21 expression is paradoxically elevated in obese conditions. Here, we sought to determine the effects of obesity prevention by daily exercise (EX) vs. caloric restriction (CR) on hepatic FGF-21 in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Four-week-old male OLETF rats were randomized into groups (n = 7–8 per group) of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or CR (OLETF-CR; 70% of SED) until 40 weeks of age. Nonhyperphagic, Long-Evans Tokushima Otsuka (LETO-SED) rats served as controls. Both daily EX and CR prevented obesity and NAFLD development observed in the OLETF-SED animals. This was associated with significantly (p < 0.01) lower serum FGF-21 (~80% lower) and hepatic FGF-21 mRNA expression (~65% lower) in the OLETF-EX and OLETF-CR rats compared with the OLETF-SED rats. However, hepatic FGF-21 protein content was reduced to the greatest extent in the OLETF-EX animals (50% of OLETF-SED) and did not differ between the OLETF-SED and OLETF-CR rats. Hepatic FGF-21 signaling mediators — hepatic FGF-21 receptor 2 (FGFR2, mRNA expression), hepatic FGF-21 receptor substrate 2 (FRS2, protein content), and co-receptor β-Klotho (protein content) — were all elevated (60%–100%, ~40%, and +30%–50%, respectively) in the OLETF-EX and OLETF-CR animals compared with the OLETF-SED animals. Daily exercise and caloric restriction modulate hepatic FGF-21 and its primary signaling mediators in the hyperphagic OLETF rat. Enhanced metabolic action of FGF-21 may partially explain the benefits of exercise and caloric restriction on NAFLD outcomes.

scholarly journals Altered basal and stimulated accumbens dopamine release in obese OLETF rats as a function of age and diabetic status

2007 ◽  
Vol 293 (2) ◽  
pp. R603-R611 ◽  
Author(s):  
Elmira Anderzhanova ◽  
Mihai Covasa ◽  
Andras Hajnal
Keyword(s):  
Strain Difference ◽  
Age Groups ◽  
Oletf Rats ◽  
Net Flux ◽  
Long Evans ◽  
Dopamine Efflux ◽  
Oletf Rat ◽  
High Calorie

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is hyperphagic, prefers palatable and high-calorie meals, and gradually develops obesity and type 2 diabetes. To determine dopamine levels in this strain, we used in vivo quantitative (no net flux) microdialysis at three different ages representing nondiabetic (8 wk), prediabetic (18 wk), and diabetic (56 wk) stages in OLETF and age-matched lean Long-Evans Tokushima Otsuka (LETO) controls. Results showed significantly elevated basal dopamine levels in the caudomedial nucleus accumbens of OLETF rats compared with LETO at younger ages (8 wk: 20.10 ± 5.61 nM vs. 15.85 ± 5.63 nM; 18 wk: 7.37 ± 3.71 nM vs. 4.75 ± 1.25 nM, means ± SD). In contrast, at 56 wk of age, a profound decline in extracellular dopamine concentrations was seen in both strains with a tendency for a greater effect in OLETF rats (1.78 ± 0.40 nM vs. 2.39 ± 0.42 nM). Further, extracellular fraction, an index for reuptake, was higher in 56-wk-old OLETF compared with LETO (0.648 ± 0.049 vs. 0.526 ± 0.057). Potassium-stimulated dopamine efflux revealed an increased capacity of vesicular pool in OLETF rats compared with LETO across all age groups with an accentuated strain difference at 56 wk. These findings demonstrate altered striatal dopamine functions (i.e., increased stimulated release and uptake) in obese OLETF rat. This could be due to the lack of functional CCK-1 receptors, or metabolic and hormonal factors associated with the development of obesity and insulin resistance, or both.

scholarly journals Toward an animal model of childhood-onset obesity: follow-up of OLETF rats during pregnancy and lactation

2009 ◽  
Vol 296 (2) ◽  
pp. R224-R232 ◽  
Author(s):  
Mariana Schroeder ◽  
Liat Shbiro ◽  
Orna Zagoory-Sharon ◽  
Timothy H. Moran ◽  
Aron Weller
Keyword(s):  
Genetic Mutation ◽  
Nursing Time ◽  
Childhood Onset ◽  
Oletf Rats ◽  
Abnormal Eating ◽  
Pregnancy And Lactation ◽  
High Investment ◽  
Long Evans ◽  
Oletf Rat

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of obesity (a spontaneous CCK1 receptor knockout) has been extensively studied as model of hyperphagia-induced obesity. In previous studies, young OLETF rats presented abnormal eating patterns [compared with Long-Evans Tokushima Otsuka (LETO) controls] in a variety of independent ingestion and nursing tests during the suckling period. The aim of the present study was to characterize the early emergence of abnormal adiposity in the pups. Moreover, because both the dams and the pups present the genetic mutation, a close follow-up of the dams' body weight and intake during pregnancy and lactation was performed to examine the circumstances that contribute to build up the pups' early adiposity. Compared with controls, OLETF pups presented higher fat levels, larger adipocytes, and increased waist circumference as early as postnatal day 7 and this profile persisted to the age of weaning. While LETO dams gained weight throughout pregnancy and lactation, OLETF dams were obese and hyperphagic during pregnancy but lost weight during lactation, probably as a result of rearing hyperphagic pups. Current and previous results suggest a possible influence of the dams' obesity during gestation and a high investment in nursing time during lactation on the pups' obesity levels during childhood. This, combined with the innate hyperphagia repeatedly observed in the pups at these early ages, makes the OLETF strain a useful tool in the research of childhood-onset obesity.

scholarly journals Physical activity maintains aortic endothelium-dependent relaxation in the obese type 2 diabetic OLETF rat

2010 ◽  
Vol 298 (6) ◽  
pp. H1889-H1901 ◽  
Author(s):  
Aaron K. Bunker ◽  
Arturo A. Arce-Esquivel ◽  
R. Scott Rector ◽  
Frank W. Booth ◽  
Jamal A. Ibdah ◽  
...  
Keyword(s):  
Physical Activity ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Physically Active ◽  
Oletf Rats ◽  
Aortic Endothelium ◽  
Long Evans ◽  
Endothelium Dependent Relaxation ◽  
Oletf Rat

We tested the hypothesis that physical activity can attenuate the temporal decline of ACh-induced endothelium-dependent relaxation during type 2 diabetes mellitus progression in the Otsuka Long-Evans Tokushima fatty (OLETF) rat. Sedentary OLETF rats exhibited decreased ACh-induced abdominal aortic endothelium-dependent relaxation from 13 to 20 wk of age (20–35%) and from 13 to 40 wk of age (35–50%). ACh-induced endothelium-dependent relaxation was maintained in the physically active OLETF group and control sedentary Long-Evans Tokushima Otsuka (LETO) group from 13 to 40 wk of age. Aortic pretreatment with NG-nitro-l-arginine (l-NNA), indomethacin (Indo), and l-NNA + Indo did not alter the temporal decline in ACh-induced endothelium-dependent relaxation. Temporal changes in the protein expression of SOD isoforms in the aortic endothelium or smooth muscle did not contribute to the temporal decline in ACh-induced endothelium-dependent relaxation in sedentary OLETF rats. A significant increase in the 40-wk-old sedentary LETO and physically active OLETF rat aortic phosphorylated endothelial nitric oxide (p-eNOS)-to-eNOS ratio was observed versus 13- and 20-wk-old rats in each group that was not seen in the 40- versus 13- and 20-wk-old sedentary OLETF rats. These results suggest that temporal changes in the antioxidant system, EDHF, and cycloxygenase metabolite production in sedentary OLETF rat aortas do not contribute to the temporal decline in sedentary OLETF rat aortic ACh-induced endothelium-dependent relaxation seen with type 2 diabetes mellitus progression. We also report that physical activity in conjunction with aging in the OLETF rat results in a temporal increase in the aortic endothelial p-eNOS-to-eNOS ratio that was not seen in sedentary OLETF rats. These results suggest that the sustained aortic ACh-induced endothelium-dependent relaxation in aged physically active OLETF rats may be the result of an increase in active aortic eNOS.

Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats

1995 ◽  
Vol 268 (3) ◽  
pp. E531-E536 ◽  
Author(s):  
M. Otsuki ◽  
T. Akiyama ◽  
H. Shirohara ◽  
S. Nakano ◽  
K. Furumi ◽  
...  
Keyword(s):  
Serum Glucose ◽  
Diabetic Rats ◽  
Exocrine Function ◽  
Guanine Nucleotide Binding Protein ◽  
Rat Serum ◽  
Pancreatic Acini ◽  
Isolated Pancreatic Acini ◽  
Long Evans ◽  
Oletf Rat

Pancreatic exocrine function of a new inbred strain Otsuka Long-Evans Tokushima Fatty (OLETF) rat that develops spontaneous persistent hyperglycemia was evaluated in in vitro isolated pancreatic acini and compared with that in the control Long-Evans Tokushima Otsuka (LETO) rat. Serum glucose and insulin concentrations in the OLETF rats were significantly high (glucose: 270 +/- 12 vs. 208 +/- 10 mg/100 ml, P < 0.01; insulin: 12.4 +/- 1.7 vs. 4.9 +/- 0.6 ng/ml, P) < 0.01), whereas pancreatic wet weight was significantly low (803 +/- 20 vs. 1,138 +/- 17 mg, P < 0.01) compared with those in the LETO rat. Pancreatic acini isolated from the OLETF rat were totally insensitive to cholecystokinin (CCK)-8 stimulation at concentrations of up to 100 nM. However, neither the responsiveness nor the sensitivity to carbamylcholine, bombesin, and secretin of the acini from the OLETF rat was altered or even increased, probably due to the larger amylase content in the OLETF rat acini compared with those of the LETO rat acini (31.5 +/- 2.0 vs. 13.0 +/- 1.1 Somogyi units/micrograms DNA, P < 0.01). The responsiveness to fluoride, a direct activator of guanine nucleotide-binding protein, in the OLETF rat acini was similar to that in the LETO rat, suggesting that the transmembrane signaling and effectors and subsequent intracellular signal transduction molecules in the OLETF rat acini are normal. Moreover, 125I-CCK binding to the acini prepared from the OLETF rat was totally absent. These present results indicate that the OLETF rat has a selective defect in the binding of CCK to its receptors on the acinar cell surface.

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