Genetics of obesity of Zucker rats and Koletsky rats.

The breeding data on Zucker rats and on Koletsky rats confirm that the obesity in these two strains of rats is inherited recessively and results from single gene mutations. Mating a Zucker heterozygote to a Koletsky heterozygote produced obese F1 progeny. Inter-stock breeding results indicate that the obesity in the Zucker-Koletsky hybrid stock is also inherited in a recessive manner. The gene that controls obesity in the Zucker rats, fatty (fa), and the gene that controls obesity in the Koletsky rats, f, are thus alleles at the same locus. We propose that f be renamed fak until it can be proven that fa and fak are identical.     

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60?mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10?mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65?days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15?days) but also in the long term (45?days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.     

Regeneration and transplantation of muscles in old rats and between young and old rats.

In order to compare the regenerative ability of skeletal muscle between young (5 month) and old (26 month) rats, sliced or intact extensor digitorum longus muscles were freely autografted into young and old rats and also reciprocally grafted from young to old inbred animals and vice versa. Sixty days after grafting, the transplants were analyzed for contractile and histochemical properties. There was a relative similarity between the contraction times of both normal control muscles and of all groups of transplants, although the contraction time tended to be prolonged and histochemical fiber pattern was more often found to be uniform in grafts of senescent animals. All groups of transplants possessed histochemically heterogeneous fiber types at 60 days. The experiments demonstrate that skeletal muscle in old rats possesses a substantial degree of regenerative ability and that the free tranpllantation of entire muscles in old animals is feasible.     

Placentas from spontaneously hypertensive rats and control strain Wistar-Kyoto rats

Placentas from spontaneously hypertensive rats (SHR) were compared to those of control strain Wistar-Kyoto rats (WKY) at 15, 18 and 20 days of gestation using light microscopic techniques. Placental lesions similar to those in pregnant hypertensive women were absent in both strains; however, other abnormalities were noted. Hemorrhage at the lateral edges of the decidua basalis appeared to be more extensive in the SHR than WKY at 15 days. At the same time, bloody vaginal discharges were noted in 18% of the SHR. Leukocytic encapsulation of 20-day placentas with viable fetuses was noted in two SHR dams but not in any WKY. It is thought that these differences may be related to the high maternal blood pressure in the SHR or to hormonal imbalance associated with the stress response in the SHR due to frequent monitoring of blood pressure.     

Of rats and men

A report on the third biannual 'Rat Genomics and Models' meeting, Cold Spring Harbor, USA, 11-14 December 2003.     

Glycogen synthase R in livers of starved rats and starved rats given glucose

We reported that when synthase D was converted to synthase I in a rat liver extract, it progressed through a synthase form with activity characteristics which could not be explained by a mixture of synthase D and synthase I (Tan, A. W. H. (1981) Biochem. J. 200, 169-172). In this study we will borrow the "R" nomenclature to describe this "non-D" and "non-I" activity. Using activities measured at five different conditions and simultaneous equations, the amount of the three synthase forms in liver extracts can be estimated. During incubation of the liver extract, the amount of synthase R was found to increase with time and then to decrease as synthase I was generated, a profile typical of an enzyme intermediate. We investigated for the presence of synthase R in rat liver under different in vivo conditions. In contrast to the liver of fed rats which had very little synthase R, the liver of fasted rats was found to have 30% of its synthase in the R form. This synthase R was increased 2-fold when glucose was given and decreased to a very low level when glucagon was given. Synthase I was not detected, even in the livers of starved rats given glucose. Using conditions which were closer to those of the cell, synthase R was found to have relatively high activity, up to 70% that of synthase I. Based on these results, synthase R is proposed to be an active enzyme form responsible for glycogen synthesis in rat liver.     

Biochemical studies of bone from diabetic rats and rats bearing transplanted pancreatic islets

A comparison of lysozymal enzymes involved in glycosaminoglycan metabolism in cortical bone found significantly increased activity in the presence of streptozotocin-induced diabetes. The presence of transplanted pancreatic islets and restitution of the normal systemic insulin and glucose values did not alter these changes. The enzyme activity of cancellous bone appeared to be even less responsive to diabetic pathology with changes developing only with advancing age.     

Tissue-specific distribution of uncoupling proteins in normal rats and rats with high-fat-diet-induced obesity

Uncoupling proteins (UCPs) are a proton transporter family located in the mitochondrial inner membrane. Thus far, five molecules (UCP1–UCP5) have been identified as members of the UCP family. Recently, UCPs have attracted considerable interest in research on energy metabolism and obesity. However, to date, no study has focused on a comprehensive and systematic evaluation of the tissue-specific distribution of UCPs in obese individuals. Our study presents evidence of differential tissue expression profiles of five isoforms of UCPs in normal and diet-induced obese (DIO) rats using real-time polymerase chain reaction (PCR) analysis. The results clearly show that the tissue-specific expression patterns of individual isoforms between DIO and normal rats are quite distinct, which suggests a close relationship between the alterations in UCP expression and dietary obesity.