Development of Ethyl Methanesulfonate Mutant Edamame Soybean (Glycine max (L.) Merr.) Populations and Forward and Reverse Genetic Screening for Early-Flowering Mutants.

Induced mutation is a viable breeding strategy that is widely utilized in the development of elite plant varieties. We aimed to improve a variety of edamame by constructing novel mutant populations using the ethyl methanesulfonate in soybeans (Glycine max (L.) Merr.). In the M2 population, the flowering stage showed a considerable standard deviation compared to the wild type, confirming that the mutant populations had the expected DNA mutations. To identify the DNA mutations in the mutant populations, we used the targeting induced local lesions in genomes (TILLING) method, which is a reverse genetic method, to search for soybean flowering-related gene mutants. A total of 30 mutants from E1, E3, E4, and PhyA1 genes, which are known to be highly effective genes, or their homologous gene for flowering and maturation found in soybean quantitative trait locus analyses were isolated from our TILLING screening. Among these mutants, there were eleven nonsynonymous substitution mutants, one nonsense mutant, and two single nucleotide deletion mutants that could be expected to reduce or eliminate gene function. The e1, e3, and e4 mutants obtained in this study flowered considerably earlier than the wild type. In particular, the e1 mutant with a nonsynonymous substitution flowered approximately 1 month after sowing regardless of the sowing date, and its harvest date was approximately 1 month earlier than that of the wild type. Mutations identified using the TILLING method could not only be used as gel-based DNA markers with the same manipulation method, but the mutations could also be detected as DNA markers by the high-resolution melting method. These results indicate that mutations achieved without chromosome modification by crossbreeding are effective for early and practical improvement of superior varieties and that efficient selection of mutants by reverse genetics is an effective method for the identification of genetic modifications. The edamame mutant populations developed in this study are believed to possess various useful alleles which may be applicable in the search for mutations that lead to improved edamame yield and eating quality beyond the flowering stage.

Treatment practices and costs among patients with psoriatic arthritis: A Japanese hospital claims database analysis.

OBJECTIVE: Assess patient characteristics, real-world treatment patterns, and health care resource utilization (HCRU) among patients with psoriatic arthritis (PsA) in Japan. METHODS: Patients diagnosed with PsA from April 2009 through July 2017 were identified from the Medical Data Vision database. Patient characteristics, treatment patterns, and HCRU were evaluated for these patients. RESULTS: A total of 639 patients met inclusion criteria and were included in the analysis for patients with a PsA diagnosis. Over 12 months following diagnosis, patients received oral NSAIDs (61.7%), conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (55.1%), corticosteroids (35.1%), topical NSAIDs (34.0%), adalimumab (14.7%), infliximab (9.7%), secukinumab (5.0%), ustekinumab (4.5%), ixekizumab (1.6%), and golimumab (1.6%). A total of 227 (35.5%) patients initiated biologic DMARDs (bDMARDs) over the median 25.2 months of study follow-up. Compared with the overall group of patients diagnosed with PsA, patients who initiated bDMARDs had higher median total per-patient health care costs ($27,772 vs. $11,316), lower median per-patient hospitalization costs ($31,164 vs. $39,359), and fewer median hospital days per admission (8.0 vs. 12.0 days). CONCLUSION: This study presents knowledge of the current state of patient characteristics, treatment patterns, HCRU, and costs among patients with PsA in Japan. Considering the relatively recent guideline recommendations, the preliminary treatment patterns suggest physicians may be following treatment guidelines.

Genome sequence comparison between Chinese hamster ovary (CHO) DG44 cells and mouse using end sequences of CHO BAC clones based on BAC-FISH results.

Chinese hamster ovary (CHO) cells have frequently been used in biotechnology as a mammalian host cell platform for expressing genes of interest. Previously, we constructed a detailed physical chromosomal map of the CHO DG44 cell line by fluorescence in situ hybridization (FISH) imaging using 303 bacterial artificial chromosome (BAC) clones as hybridization probes (BAC-FISH). BAC-FISH results revealed that the two longest chromosomes were completely paired. However, other chromosomes featured partial deletions or rearrangements. In this study, we determined the end sequences of 303 BAC clones (BAC end sequences), which were used for BAC-FISH probes. Among 606 BAC-end sequences (BESs) (forward and reverse ends), 558 could be determined. We performed a comparison between all determined BESs and mouse genome sequences using NCBI BLAST. Among these 558 BESs, 465 showed high homology to mouse chromosomal sequences. We analyzed the locations of these BACs in chromosomes of the CHO DG44 cell line using a physical chromosomal map. From the obtained results, we investigated the regional similarities among CHO chromosomes (A-T) and mouse chromosomes (1-19 and sex) about 217 BESs (46.7% of 465 high homologous BESs). Twenty-three specific narrow regions in 13 chromosomes of the CHO DG44 cell line showed high homology to mouse chromosomes, but most of other regions did not show significant correlations with the mouse genome. These results contribute to accurate alignments of chromosomes of Chinese hamster and its genome sequence, analysis of chromosomal instability in CHO cells, and the development of target locations for gene and/or genome editing techniques.

Real-world effectiveness of daily teriparatide in Japanese patients with osteoporosis at high risk for fracture: final results from the 24-month Japan Fracture Observational Study (JFOS).

OBJECTIVE: The Japan Fracture Observational Study (JFOS), a prospective observational study, investigated the real-world effectiveness of daily teriparatide to reduce clinical fracture risk in osteoporotic patients. METHODS: In routine clinical practice, Japanese patients initiated on teriparatide 20 µg/day by subcutaneous injection were enrolled. The primary end-point was the rate of clinical fractures at 6-month intervals over 24 months. Bone mineral density (BMD), procollagen type 1 aminoterminal propeptide (P1NP), back pain, and health-related quality-of-life (HRQoL) information was collected. RESULTS: Of 1,996 patients at baseline, 90.1% were female, and mean age was 76.9 years. Teriparatide persistence at 12 and 24 months was 68.0% and 51.6%, respectively. Compared to the first 6-month treatment interval, the odds ratio of fractures decreased by 56.4% during 6-12 months, 51.6% during 12-18 months, and 58.8% during 18-24 months (all p < .01). After 24 months, BMD increased by 17.2% (lumbar spine) and 7.9% (total hip). After 6 months, P1NP levels increased by 259.3%. A reduction in back pain (100 mm visual analog scale) of 16.1 mm at 3 months was maintained through 24 months. HRQoL (pain, daily living activities, general health) improved by ≥10% at each post-baseline time point. Of 279 (14.6%) patients with ≥1 adverse event (AE), 71 (3.7%) experienced ≥1 drug-related AE (investigator assessed), including nausea (0.7%), dizziness (0.4%), and decreased appetite (0.3%). Osteosarcoma was not reported; there were no new safety signals. CONCLUSIONS: JFOS demonstrated effectiveness of teriparatide 20 µg/day to reduce the risk of clinical fractures in Japanese patients in a real-world setting.

Understanding the factors associated with initiation and adherence of osteoporosis medication in Japan: An analysis of patient perceptions.

OBJECTIVES: This study aimed to identify factors associated with initiation and adherence of osteoporosis medication from a patient perspective. METHODS: A web-based survey was developed based on health behavior theories. Descriptive analyses were conducted for all survey items. Analyses in a structural equation modeling framework were conducted to identify factors associated with treatment initiation and adherence. RESULTS: Five hundred forty-five women completed the questionnaire. A majority were currently receiving medications for osteoporosis (n = 376, 69.0%) and 25.0% of these patients (n = 94) were considered adherent to their treatment. Knowledge was strongly associated with osteoporosis treatment initiation (standard error [SE], 0.58). Greater knowledge of disease was associated with increased likelihood of initiating medication. Medication complexity (SE, 0.49) and perceived susceptibility to fracture and loss of independence (SE, -0.37) were also associated with initiation. Perceived barriers (SE, -0.85) such as inconvenience, lack of efficacy and financial burden were observed to be the greatest obstacle to adherence. The greater the perceived barriers, the less likely patients were to adhere to medication. Patients' perception of self-efficacy (SE, 0.37) also affected adherence. The greater the patient perception of ability to independently manage their medication, the more likely they were to adhere to the medication. CONCLUSIONS: Different factors were found to be associated with initiation and adherence of osteoporosis medication. Patient knowledge of their disease and the perception of barriers were found to be the most influential. Empowering patients with the knowledge to better understand their disease and decreasing the perception of barriers through education initiatives may be effective in improving patient outcomes.

Bone morphological analyses in Spontaneously Diabetic Torii (SDT) fatty rats.

The Spontaneously Diabetic Torii (SDT) fatty rat, a model for obese type 2 diabetes, shows bone quantitative abnormalities, namely low bone mineral density (BMD). The objective of this study was to evaluate bone morphological changes, in particular identifying the bone qualitative abnormalities, in the SDT fatty rat. Male SDT fatty rats showed increases in total trabecular area and trabecular number and decreases in trabecular thickness in cancellous bones of the proximal tibia, indicating trabecular miniaturization. The SDT fatty rat is useful for investigation of pathophysiological changes in bone quality in diabetic osteoporosis.

Dihydroquercetin (DHQ) ameliorated concanavalin A-induced mouse experimental fulminant hepatitis and enhanced HO-1 expression through MAPK/Nrf2 antioxidant pathway in RAW cells.

Autoimmune hepatitis represents a ubiquitous human health problem and has a poor prognosis. Dihydroquercetin (DHQ), a well-known antioxidant, significantly inhibits fulminant hepatitis through anti-oxidant and anti-inflammation mechanisms. In this study, we show that administration of DHQ ameliorated concanavalin A (ConA)-induced mouse liver injury by increasing the survival rate, reducing the serum ALT and AST level, preventing histopathological injuries and decreasing pro-inflammatory cytokine mRNA expression in hepatic tissue. As macrophages/Kupffer cells in oxidative stress and pro-inflammatory mediators play an important role in the pathogenesis of immune-mediated hepatitis, we further exposed mouse RAW264 macrophage cell lines to ConA in vitro and found that DHQ significantly inhibited mRNA expression and secretion of IFN-γ and TNF-α in cell culture supernatant. In addition, DHQ significantly enhanced heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner via increased Nrf2 expression in cytoplasm and nuclear translocation. Furthermore, DHQ enhanced phosphorylation of three members of the mitogen-activated protein kinase (MAPK) family, and cell treatment with MEK/ERK (PD98059), p38 (SB203580) and JNK (SP600125) inhibitors reduced DHQ-induced HO-1 expression. These results indicate that DHQ possesses hepatoprotective properties against ConA-induced liver injury, which are attributed to its ability to scavenge oxidative stress and to inhibit the release of inflammatory mediators via upregulation of HO-1 activity through the MAPK/Nrf2 signaling pathway in macrophages/Kupffer cells.

Gender differences in metabolic disorders and related diseases in Spontaneously Diabetic Torii-Lepr(fa) rats.

The Spontaneously Diabetic Torii Lepr(fa) (SDT fatty) rat is a novel type 2 diabetic model wherein both male and female rats develop glucose and lipid abnormalities from a young age. In this study, we investigated gender differences in abnormalities and related complications in SDT fatty rats. Food intake was higher in males compared to female rats; however, body weight was not different between genders. Progression of diabetes, including increases in blood glucose and declines in blood insulin, was observed earlier in male rats than in females, and diabetic grade was more critical in male rats. Blood lipids tended to increase in female rats. Gonadal dysfunction was observed in both male and female rats with aging. Microangiopathies, such as nephropathy, retinopathy, neuropathy, and osteoporosis, were seen in both genders, and pathological grade and progression were more significant in males. Qualitative and quantitative changes were observed for metabolic disease gender differences in SDT fatty rats. The SDT fatty rat is a useful model for researching gender differences in metabolic disorders and related diseases in diabetes with obesity.

Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Lepr (fa) Rat: A New Obese Type 2 Diabetic Model.

Spontaneously Diabetic Torii Lepr (fa) (SDT fatty) rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

Community-based intervention to improve dietary habits and promote physical activity among older adults: a cluster randomized trial.

BACKGROUND: The fastest growing age group globally is older adults, and preventing the need for long-term nursing care in this group is important for social and financial reasons. A population approach to diet and physical activity through the use of social services can play an important role in prevention. This study examined the effectiveness of a social health program for community-dwelling older adults aimed at introducing and promoting physical activity in the home at each individual's pace, helping participants maintain good dietary habits by keeping self-check sheets, and determining whether long-standing unhealthy or less-than-ideal physical and dietary habits can be changed. METHOD: This cluster randomized trial conducted at 6 community centers in an urban community involved 92 community-dwelling older adults aged 65-90 years. The intervention group (3 community centers; n = 57) participated in the social health program "Sumida TAKE10!" which is an educational program incorporating the "TAKE10!® for Older Adults" program, once every 2 weeks for 3 months. The control group (3 community centers; n=35) was subsequently provided with the same program as a crossover intervention group. The main outcome measures were changes in food intake frequency, food frequency score (FFS), dietary variety score (DVS), and frequency of walking and exercise. The secondary outcome measures were changes in self-rated health, appetite, and the Tokyo Metropolitan Institute of Gerontology (TMIG) Index of Competence score. RESULTS: Compared to baseline, post-intervention food intake frequency for 6 of 10 food groups (meat, fish/shellfish, eggs, potatoes, fruits, and seaweed), FFS, and DVS were significantly increased in the intervention group, and interaction effects of FFS and DVS were seen between the two groups. No significant differences were observed between baseline and post-intervention in the control group. Frequency of walking and exercise remained unchanged in both groups, and no significant difference in improvement rate was seen between the groups. Self-rated health was significantly increased in the intervention group. Appetite and TMIG Index of Competence score were unchanged in both groups. CONCLUSIONS: The social health program resulted in improved dietary habits, as measured by food intake frequency, FFS, and DVS, and may improve self-rated health among community-dwelling older adults. TRIAL REGISTRATION NUMBER: UMIN000007357.

Parathyroid hormone (1-34) improves bone mineral density and glucose metabolism in Spontaneously Diabetic Torii-Lepr(fa) rats.

The Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat, a model of obese type 2 diabetes, shows obesity, hyperglycaemia and low bone mineral density (BMD). The objective of this study is to evaluate the effects of parathyroid hormone (1-34) [PTH(1-34)] on BMD and glucose metabolism in the SDT-fa/fa rat. SDT-fa/fa rats showed obesity with hyperglycaemia and decreased serum osteocalcin levels and the tibial BMD. A 4-week treatment of PTH(1-34) (20 µg/kg/day) increased the serum osteocalcin levels and the tibial BMD, and decreased the serum glucose levels without changing the serum insulin levels. These findings indicate that PTH(1-34) improved not only BMD but also glucose metabolism in SDT-fa/fa rats. This study suggests that PTH(1-34) is a novel agent for the treatment of diabetic osteoporosis.

Characteristics of bone turnover, bone mass and bone strength in Spontaneously Diabetic Torii-Lepr fa rats.

The Spontaneously Diabetic Torii-Lepr (fa) (SDT-fa/fa) rat is a new model of obese type 2 diabetes. The SDT-fa/fa rat shows obesity and hyperglycemia at a young age compared to the Spontaneously Diabetic Torii (SDT-+/+) rat; however, bone abnormalities in the SDT-fa/fa rat have not been investigated. The objective of the present study was to investigate the effects of obese type 2 diabetes on bone turnover, bone mass, and bone strength in the SDT-fa/fa rat. Sprague-Dawley rats were used as control animals, and SDT-+/+ rats were used as non-obese type 2 diabetic rats. Serum osteocalcin and urine deoxypyridinoline levels were decreased in SDT-fa/fa rats compared to control rats at a young age. SDT-fa/fa rats showed decreases in bone mineral density and bone mineral content of the whole tibia, and shortening of the tibia and femur compared to control and SDT-+/+ rats. Deterioration in bone geometrical properties of the femur midshaft such as cortical thickness and minimum moment of inertia, was observed in SDT-fa/fa rats compared to control and SDT-+/+ rats. Furthermore, trabecular bone volume of the distal femur was decreased in SDT-fa/fa rats compared to control rats. These negative effects on bone in SDT-fa/fa rats caused severe decreases in maximum load, stiffness, and energy absorption of the femur. In addition, serum levels of homocysteine, a candidate for bone fragility markers, were elevated in SDT-fa/fa rats compared to control and SDT-+/+ rats. In conclusion, the SDT-fa/fa rat may be a useful model to investigate bone abnormalities in obese type 2 diabetes.

Construction of BAC-based physical map and analysis of chromosome rearrangement in Chinese hamster ovary cell lines.

Chinese hamster ovary (CHO) cells have frequently been used in biotechnology for many years as a mammalian host cell platform for cloning and expressing genes of interest. A detailed physical chromosomal map of the CHO DG44 cell line was constructed by fluorescence in situ hybridization (FISH) imaging using randomly selected 303 BAC clones as hybridization probes (BAC-FISH). The two longest chromosomes were completely paired chromosomes; other chromosomes were partly deleted or rearranged. The end sequences of 624 BAC clones, including 287 mapped BAC clones, were analyzed and 1,119 informative BAC end sequences were obtained. Among 303 mapped BAC clones, 185 clones were used for BAC-FISH analysis of CHO K1 chromosomes and 94 clones for primary Chinese hamster lung cells. Based on this constructed physical map and end sequences, the chromosome rearrangements between CHO DG44, CHO K1, and primary Chinese hamster cells were investigated. Among 20 CHO chromosomes, eight were conserved without large rearrangement in CHO DG44, CHO K1, and primary Chinese hamster cells. This result suggested that these chromosomes were stable and essential in CHO cells and supposedly conserved in other CHO cell lines.

Fluorescence in situ hybridization using bacterial artificial chromosome (BAC) clones for the analysis of chromosome rearrangement in Chinese hamster ovary cells.

Chromosome identification using Chinese hamster ovary (CHO) genomic bacterial artificial chromosome (BAC) clones has the potential to contribute to the analysis and understanding of chromosomal instability of CHO cell lines and to improve our understanding of chromosome organization during the establishment of recombinant CHO cells. Fluorescence in situ hybridization imaging using BAC clones as probes (BAC-FISH) can provide valuable information for the identification of chromosomes. In this study, we identified chromosomes and analyzed the chromosome rearrangement in CHO cells using BAC-FISH methods.

JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 µg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

Effects of ovariectomy on bone metabolism and bone mineral density in spontaneously diabetic Torii-Lepr(fa) rats.

The Spontaneously Diabetic Torii-Lepr(fa) (SDT- fa/fa) rat is a new model of obese type 2 diabetes. The female SDT-fa/fa rat shows obesity, hyperglycemia and hyperlipidemia from a young age. However, it is not known whether diabetes and estrogen deficiency can lead to bone abnormalities in the female SDT-fa/fa rat. The objective of the present study was to investigate the effects of ovariectomy (OVX) on bone metabolism and bone mineral density (BMD) in the female SDT-fa/fa rat. Female Sprague-Dawley rats were used as control animals. The BMDs of the whole tibia and fifth lumbar (L5) vertebral body were analyzed at 30 weeks after OVX. Serum osteocalcin, a bone formation marker, and urine deoxypyridinoline (DPD), a bone resorption marker, were sequentially analyzed before and at 5, 15 and 30 weeks after OVX. Serum osteocalcin and urine DPD levels were lower in SDT-fa/fa rats than in control rats before OVX. Both serum osteocalcin and urine DPD levels were elevated in control rats 5-30 weeks after OVX, but only the urine DPD levels were elevated in SDT-fa/fa rats 5-30 weeks after OVX. SDT-fa/fa rats showed a decrease in the BMDs of the whole tibia and L5 vertebral body compared with control rats. OVX decreased the BMDs of the whole tibia and L5 vertebral body in control rats, but not in SDT-fa/fa rats. These data suggest that estrogen deficiency is not a risk factor for bone loss in type 2 diabetes mellitus.

Discovery of a potent and short-acting oral calcilytic with a pulsatile secretion of parathyroid hormone.

Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have been considered as alternatives for parathyroid hormone (PTH), an injectable bone anabolic drug used in the treatment of osteoporosis. Previously, we identified aminopropandiol 1, which transiently stimulated endogenous PTH secretion in rats. However, the inhibition of cytochrome P450 (CYP) 2D6 and the low bioavailability of 1 remain to be solved. Attempts to change the physicochemical properties of the highly lipophilic amine 1 by introduction of a carboxylic acid group as well as further structural modifications led to the discovery of the highly potent biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a significantly improved bioavailability. Compound 15 evoked a rapid and transient elevation of endogenous PTH levels in rats after oral administration in a dose-dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern correlated with the pharmacokinetic profile and agreed well with that of the exogenous PTH injection which exerts a bone anabolic effect.

Glycemic index and postprandial blood glucose response to Japanese strawberry jam in normal adults.

We investigated in 30 healthy adults the glycemic index (GI) of five strawberry jams made from various sugar compositions. The jam containing the highest ratio of glucose showed a high GI, while that containing a high ratio of fructose, a jam made from polydextrose, showed a low GI. There was a high correlation (r=0.969, p=0.006) between the GI and the predicted GI calculated from the sugar composition of the jams. Moreover, the influence on postprandial blood glucose response after an intake of only 20 g of jam and one slice of bread with 20 g jam was measured in 8 healthy adults. The blood glucose level after an intake of 20 g of the high GI jam containing the high glucose ratio was higher than that of other jams at 15 min, but there was no significant difference after 30 min. Regardless of whether the GI was low or high, differences in the jams were not observed in the postprandial blood glucose level or the area under the curve after eating either one slice of bread (60 g) or one slice of bread with less than 20 g of jam.

Effect of severe maternal dietary restriction on growth and intra-abdominal adipose tissue weights in offspring rats.

In Japan, the number of low weight birth babies is increasing. The increase in the number of slim young women is considered to be associated with the rising number of low birth weight babies in Japan. In 1993, Barker et al. published highly influential findings indicating a relationship between low birth weight and increased risk of developing symptoms of metabolic syndrome. Here, we report on results that occur when dietary restriction is applied during all periods of pregnancy. It was shown that, at 5 d, the mean weight of pups in the dietary restriction group was lower than the mean weight of pups in the control group. Catch-up growth began when milk yields of the dietary restriction group pups attained the same levels as those of the control group pups. Intra-abdominal adipose tissue weights of the dietary restricted group were significantly higher than those of the control group in males at 280 d after birth. Intra-abdominal adipose tissue weights of the dietary restricted group had a tendency to be higher than those of the control group for female rats. In male rats, it is considered that increase in intra-abdominal adipose tissue is related to lean body mass but it is not related to the function of brown adipose tissue (BAT). In female rats, it is considered that the increase in intra-abdominal adipose tissue is related to the function of BAT and lean body mass.