Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular contractions in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat aorta

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.

Download Full-text

Proteomic method detects oxidatively induced protein carbonyls in muscles of a diabetes model Otsuka Long-evans Tokushima Fatty (OLETF) rat

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(02)01239-x ◽

2003 ◽

Vol 34 (1) ◽

pp. 11-22 ◽

Cited By ~ 49

Author(s):

Masamichi Oh-Ishi ◽

Takeshi Ueno ◽

Tadakazu Maeda

Keyword(s):

Protein Carbonyls ◽

Diabetes Model ◽

Long Evans ◽

Oletf Rat

Download Full-text

Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain

Genetics Research ◽

10.1017/s0016672301004918 ◽

2001 ◽

Vol 77 (2) ◽

pp. 183-190 ◽

Cited By ~ 8

Author(s):

SHIRO OKUNO ◽

TAKESHI K. WATANABE ◽

TOSHIHIDE ONO ◽

KEIKO OGA ◽

AYAKO MIZOGUCHI-MIYAKITA ◽

...

Keyword(s):

Therapeutic Effect ◽

Major Quantitative Trait Locus ◽

Genome Scans ◽

Fischer 344 ◽

Obesity Control ◽

Single Allele ◽

Long Evans ◽

Trait Locus ◽

F344 Rats ◽

Oletf Rat

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Download Full-text

Biochemical and Morphological Changes during Development of Sugar Cataract in Otsuka Long–Evans Tokushima Fatty (OLETF) Rat

Experimental Eye Research ◽

10.1006/exer.2001.1046 ◽

2001 ◽

Vol 73 (3) ◽

pp. 375-381 ◽

Cited By ~ 12

Author(s):

E. Kubo ◽

K. Maekawa ◽

T. Tanimoto ◽

S. Fujisawa ◽

Y. Akagi

Keyword(s):

Morphological Changes ◽

Long Evans ◽

Sugar Cataract ◽

Oletf Rat

Download Full-text

Altered Pontine Taste Processing in a Rat Model of Obesity

Journal of Neurophysiology ◽

10.1152/jn.01359.2007 ◽

2008 ◽

Vol 100 (4) ◽

pp. 2145-2157 ◽

Cited By ~ 17

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.

Download Full-text

Defect of an Early Event of Glucose Metabolism in Skeletal Muscle of the Male Otsuka Long-Evans Tokushima Fatty (OLETF) Rat, a Non-Insulin- Dependent Diabetes Mellitus (NIDDM) Model

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1998.8442 ◽

1998 ◽

Vol 245 (2) ◽

pp. 378-381 ◽

Cited By ~ 11

Author(s):

Takashi Sato ◽

Kiyohiko Magata ◽

Nobuyuki Koga ◽

Yasuhide Mitsumoto

Keyword(s):

Diabetes Mellitus ◽

Skeletal Muscle ◽

Glucose Metabolism ◽

Insulin Dependent Diabetes Mellitus ◽

Insulin Dependent Diabetes ◽

Dependent Diabetes Mellitus ◽

Early Event ◽

Insulin Dependent ◽

Long Evans ◽

Oletf Rat

Download Full-text

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00510.2010 ◽

2011 ◽

Vol 300 (5) ◽

pp. G874-G883 ◽

Cited By ~ 88

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.

Download Full-text

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

Applied Physiology Nutrition and Metabolism ◽

10.1139/h2012-091 ◽

2012 ◽

Vol 37 (6) ◽

pp. 1054-1062 ◽

Cited By ~ 24

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.

Download Full-text