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

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.

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Rats show a preference for certain unfamiliar strains of rats

10.1101/2021.02.18.431764 ◽

2021 ◽

Author(s):

Hiroki Kogo ◽

Yasushi Kiyokawa ◽

Yukari Takeuchi

Keyword(s):

Stress Responses ◽

Wistar Rat ◽

Sprague Dawley ◽

Fischer 344 ◽

The Subject ◽

Long Evans ◽

F344 Rats ◽

Anaesthetised Rats ◽

Social Behaviours

AbstractHumans show distinct social behaviours when we recognise social similarity in opponents that are members of the same social group. However, little attention has been paid to the role of social similarity in non-human animals. In Wistar subject rats, the presence of an unfamiliar Wistar rat mitigated stress responses, suggesting the importance of social similarity in this phenomenon. We found that the presence of unfamiliar Sprague-Dawley (SD) or Long-Evans (LE) rats, but not an unfamiliar Fischer 344 (F344) rat, similarly mitigated stress in subject rats. It is therefore possible that the subject rats recognised social similarity to unfamiliar SD and LE rats. In this study, we demonstrated that Wistar subject rats were capable of categorizing unfamiliar rats based on their strain, and that Wistar subjects showed a preference for unfamiliar Wistar, SD, and LE rats over F344 rats. However, the subject rats did not show a preference among Wistar, SD, and LE rats. In addition, the results were not due to an aversion to F344 rats, and preference was not affected when anaesthetised rats were presented to subject rats. The findings suggested that rats recognise social similarity to certain unfamiliar strains of rats.

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Long–Evans rats have a larger cortical topographic representation of movement than Fischer-344 rats: A microstimulation study of motor cortex in naı̈ve and skilled reaching-trained rats

Brain Research Bulletin ◽

10.1016/s0361-9230(02)00865-1 ◽

2002 ◽

Vol 59 (3) ◽

pp. 197-203 ◽

Cited By ~ 35

Author(s):

Penny M VandenBerg ◽

Theresa M Hogg ◽

Jeffrey A Kleim ◽

Ian Q Whishaw

Keyword(s):

Motor Cortex ◽

Fischer 344 Rats ◽

Fischer 344 ◽

Long Evans ◽

Topographic Representation ◽

Skilled Reaching

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Single-Allele Correction Of The Dmo1 Locus In Congenic Animals Substantially Attenuates Obesity, Dyslipidaemia And Diabetes Phenotypes Of The Oletf Rat

Clinical and Experimental Pharmacology and Physiology ◽

10.1046/j.1440-1681.2001.03391.x ◽

2001 ◽

Vol 28 (1-2) ◽

pp. 28-42 ◽

Cited By ~ 9

Author(s):

Takeshi K Watanabe ◽

Shiro Okuno ◽

Toshihide Ono ◽

Yuki Yamasaki ◽

Keiko Oga ◽

...

Keyword(s):

Single Allele ◽

Oletf Rat

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Cold-induced thermogenesis in younger and older Fischer 344 rats following exercise training

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.254.6.r908 ◽

1988 ◽

Vol 254 (6) ◽

pp. R908-R916 ◽

Cited By ~ 1

Author(s):

R. B. McDonald ◽

B. A. Horwitz ◽

J. S. Stern

Keyword(s):

Exercise Training ◽

Body Mass ◽

Cold Exposure ◽

O2 Consumption ◽

Fischer 344 ◽

Before And After ◽

Old Rats ◽

F344 Rats ◽

Maintain Body Temperature ◽

Brown Fat Mitochondria

The inability of old rats to maintain body temperature during cold exposure has been well documented. This study evaluated the effect of exercise on the rates of cold-induced O2 consumption and the contribution of nonshivering thermogenesis (NST) to these rates. Younger (12 mo) and older (24 mo) male Fischer 344 (F344) rats were divided into exercised and sedentary groups. Exercised rats were run on a motor-driven treadmill 60 min/day, at 19-24 m/min, 5 days/wk for 6 mo. At the conclusion of the 6-mo training period, O2 consumption of all four groups was measured at thermoneutrality (26 degrees C) and during 6 h of exposure to 6 degrees C. Rectal temperatures were recorded before and after cold exposure. NST was estimated from the ability of isolated brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). Core temperature of older sedentary rats fell 5.1 +/- 0.4 degrees C after cold exposure (36.3 +/- 0.3 vs. 31.2 +/- 0.8 degrees C). Exercise training in older animals prevented this fall from occurring (36.4 +/- 0.2 vs. 35.3 +/- 0.3 degrees C). Core temperatures of cold-exposed younger exercised and sedentary rats did not differ from thermoneutral values. Exercise did not alter the rates of resting body mass-independent (ml.min-1.kg body mass-0.67) O2 consumption in younger or older rats. However, body mass-independent and lean body mass (LBM)-independent (ml.min-1.g LBM-0.67) cold-induced O2 consumptions of older exercised rats were significantly elevated relative to those of older sedentary animals. This effect of exercise was not seen in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Subchronic Hepatotoxicity Evaluation of Hydrazobenzene in Fischer 344 Rats

International Journal of Toxicology ◽

10.1177/1091581812465322 ◽

2012 ◽

Vol 31 (6) ◽

pp. 564-571 ◽

Cited By ~ 7

Author(s):

Darol E. Dodd ◽

Linda J. Pluta ◽

Mark A. Sochaski ◽

Henry G. Wall ◽

Russell S. Thomas

Keyword(s):

Body Weight ◽

Serum Alkaline Phosphatase ◽

Clinical Signs ◽

Liver Weight ◽

Fischer 344 ◽

Liver Histopathology ◽

Clinical Observations ◽

Body Weights ◽

Effect Level ◽

F344 Rats

Male F344 rats were exposed to hydrazobenzene (HZB) by dietary feed at concentrations of 0, 5, 20, 80, 200, or 300 ppm for 5 days, 2 weeks, 4 weeks, or 13 weeks duration. End points evaluated included clinical observations, body weights, liver weights, serum chemistry, blood HZB, gross pathology, and liver histopathology. There were no HZB exposure-related clinical signs of toxicity. During study weeks 8 through 13, body weight means in rats of the 300 ppm group were 6% lower compared to control rat means. Serum alkaline phosphatase concentrations were decreased in rats of the 300 ppm group at all time points. Relative (to body weight) liver weight increases were observed in rats of the 200 and 300 ppm groups following 5 days (300 ppm only), 2 weeks, 4 weeks, and 13 weeks of exposure. Following 13 weeks of exposure, microscopic findings in the liver were observed only in rats of the 200 and 300 ppm groups and consisted of hypertrophy, macrovesiculation, eosinophilic granular cytoplasm, and bile duct duplication. Blood HZB concentrations ranged from 0.002 to 0.006 µg/mL in rats of the 200 or 300 ppm groups. A no observed effect level of 80 ppm (4.80 mg/kg per d) was selected based on the observation of microscopic hepatocyte alterations at ≥200 ppm HZB.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.3.e531 ◽

1995 ◽

Vol 268 (3) ◽

pp. E531-E536 ◽

Cited By ~ 1

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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