The impact of rare cancer and early-line treatments on the benefit of comprehensive genome profiling-based precision oncology.

BACKGROUND: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP. MATERIALS AND METHODS: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response. RESULTS: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively). CONCLUSION: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types.

Scenarios for modeling solar radiation modification.

Making informed future decisions about solar radiation modification (SRM; also known as solar geoengineering)-approaches such as stratospheric aerosol injection (SAI) that would cool the climate by reflecting sunlight-requires projections of the climate response and associated human and ecosystem impacts. These projections, in turn, will rely on simulations with global climate models. As with climate-change projections, these simulations need to adequately span a range of possible futures, describing different choices, such as start date and temperature target, as well as risks, such as termination or interruptions. SRM modeling simulations to date typically consider only a single scenario, often with some unrealistic or arbitrarily chosen elements (such as starting deployment in 2020), and have often been chosen based on scientific rather than policy-relevant considerations (e.g., choosing quite substantial cooling specifically to achieve a bigger response). This limits the ability to compare risks both between SRM and non-SRM scenarios and between different SRM scenarios. To address this gap, we begin by outlining some general considerations on scenario design for SRM. We then describe a specific set of scenarios to capture a range of possible policy choices and uncertainties and present corresponding SAI simulations intended for broad community use.

CHARACTERISATION OF RADIOPHOTOLUMINESCENCE DOSIMETRY SYSTEM FOR INDIVIDUAL MONITORING.

Performance evaluation is typically assessed as part of the approval procedure to verify that a dosimetry system fulfils specified national or international type-test requirements under representative exposure conditions that are expected to mimic workplace fields from the radiological activities being monitored. The International Atomic Energy Agency Radiation Safety Technical Services Laboratory has recently implemented an integrated radiophotoluminescence (RPL) personal dosimetry system developed by Chiyoda Technol Corporation. This paper reports on the successful verification of dosimetric performance properties of the RPL dosimetry system to IEC 62387:2020, in which the badges were exposed to a range of radiation energies and angles of incidence as well as other influence parameters. Characteristics under test included the coefficient of variation, non-linearity of response due to dose dependence as well as the energy and angular response to photon and beta radiation.

Electrochemical reduction of CO2 using Germanium-Sulfide-Indium amorphous glass structures.

The research in electrochemical reduction of CO2 is shifting towards the discovery of new and novel materials. This study shows a new class of material, that of Ge-S-In chalcogenide glass, to be active for reduction of CO2 in aqueous solutions. Experiments were conducted with bulk and particle form of the material, yielding different product for each structural form. Faradaic efficiency of upto 15% was observed in bulk form for CO production while formic acid with up to 26.1 % faradaic efficiency was measured in powder form. Chalcogenide studies have focused primarily on the photoelectrochemical reduction however these results provide a strong merit for introducing metal in chalcogenide glass structures for electrochemical reduction of CO2. The activity for CO2 reduction and the change in product selectivity reflects that further efforts to improve the glass structures can be undertaken in order to increase the faradaic efficiency and selectivity of the products.

Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke.

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.

Morphological characterization of small hepatocytes after bile duct ligation in chicken.

Small hepatocytes have hepatocyte-like characteristics and high proliferation activity. Most small hepatocyte studies report on in vitro rat or human hepatocytes. Only a few studies of small hepatocytes after bile duct ligation have been reported, and none of these have focused on these cells in birds. In this study, small hepatocytes appearing in bile duct ligation chicken liver were examined using the morphological method with histological, immunohistochemical, and ultrastructural studies. Nine Boris Brown hens (over 744-d old) were used. In all chickens, both the common hepatoenteric duct and hepatocystic duct were ligated, and the livers were examined 1, 4, 6, 9, and 13 weeks after bile duct ligation. Histologically, the small cells were half the size of normal liver cells, and mitotic figures were often observed. The nuclei showed two forms: large and small. Many small cells were negative for periodic acid-Schiff stain, but positive cells were rarely observed. The cells existed in colonies on the side of the sinusoid of the hepatic lamina. Immunohistochemically, the small cells with large nuclei were strongly positive for CD44, albumin and proliferation cell nuclear antigen, and the cells with small nuclei were weakly positive. In the CD44-positive cell colony, negative cells were often observed to have mature hepatocyte-like morphology. Moreover, many of the cells were PAN cytokeratin negative. Ultrastructurally, the small cells had more nuclei with rich heterochromatin, poor cytoplasmic organelles, and narrow cytoplasm with a high electron density than mature hepatocytes. Moreover, cells having a middle ultrastructural characteristic existed between the small cells and mature hepatocytes. The small hepatocellular colony of the chicken appeared as a regeneration-related change in the liver after bile duct ligation. The cell had high cell proliferation activity and morphological, immunohistochemical, and ultrastructural characteristics similar to those of the mammalian small hepatocyte, as well as a similar progenitor cell.

Effect of Lactobacillus strains on thymus and chemokine expression in keratinocytes and development of atopic dermatitis-like symptoms.

Lactobacillus strains, a major group of lactic acid bacteria, are representative food microorganisms that have many potential beneficial effects via their interactions with immune and intestinal epithelial cells. However, little is known about the effect of Lactobacillus strains on atopic dermatitis via keratinocytes, which comprise the physical barrier of the skin. In this study, we report that Lactobacillus strains have a significant suppressive effect on tumour necrosis factor (TNF)-α-induced expression and production of thymus and activation-regulated chemokine (TARC), a T helper 2 cell chemokine responsible for atopic dermatitis, in human keratinocytes. An RNA interference study showed that the effect of Lactobacillus reuteri strain Japan Collection of Microorganisms (JCM) 1112, the most suppressive strain, depended on the presence of Toll-like receptor 2 and the induction of A20 (also known as TNF-α-induced protein 3) and cylindromatosis in HaCaT cells. Topical application of a water-soluble extract of homogenised JCM 1112 cells significantly suppressed the development of house dust mite-induced atopic skin lesions and TARC expression at the lesion sites in NC/Nga mice. Our study provides new insights into the use of Lactobacillus strains as suppressive agents against keratinocyte-involved atopic inflammation of the skin.

Hepatitis B virus reactivation in patients with rheumatoid arthritis: Analysis of the National Database of Japan.

This study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76 641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti-hepatitis B virus surface antibody, and anti-hepatitis B virus core antibody were performed in 28.23%, 12.52% and 14.63% of patients, respectively, when the therapy was initiated. We found that HBV reactivation and fulminant hepatitis occurred in both the patients with and without HBV DNA monitoring, indicating insufficient monitoring in Japan during the study. The cumulative incidence of HBV reactivation over 24 months was 1.57% (95% confidence interval [CI] = 1.28%-1.92%) in the monitoring group, which consisted of those with resolved HBV infection. Glucocorticoid administration was a potent risk factor for HBV reactivation (hazard ratio [HR]  = 1.70, 95% CI = 1.26-2.29, P = .001 in all subjects, and HR = 1.82, 95% CI = 1.18-2.81, P = .007 in the nonmonitoring group), although it was not statistically significant in the monitoring group (HR = 1.49, 95% CI = 0.99-2.26 and P = .057). No significant risk difference was observed between single administration of methotrexate and biological drugs.

Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides.

The NLRP3 inflammasome, an intracellular sensor consisting of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and procaspase-1, plays critical roles in host defense against microbial pathogens by inducing production of interleukin-1ß (IL-1ß) and IL-18. Mycoplasma salivarium and Mycoplasma pneumoniae cells activated murine bone marrow-derived macrophages (BMMs) to induce production of IL-1α, IL-1ß, and IL-18. The IL-1ß production-inducing activities of these mycoplasmas toward BMMs from Toll-like receptor 2 (TLR2)-deficient mice were significantly attenuated compared with those from C57BL/6 mice (B6BMMs). This result suggests the possibility that their lipoproteins as TLR2 agonists are involved in the activity. Lipoproteins of M. salivarium and M. pneumoniae (MsLP and MpLP), and the M. salivarium-derived lipopeptide FSL-1 induced IL-1ß production by B6BMMs, but not by BMMs from caspase-1-, NLRP3- or ASC-deficient mice. The activities of MsLP and MpLP were not downregulated by the proteinase K treatment, suggesting that the active sites are their N-terminal lipopeptide moieties. B6BMMs internalized the mycoplasmal N-terminal lipopeptide FSL-1 at least 30 min after incubation, FSL-1-containing endosomes started to fuse with the lysosomes around 2 hours, and then FSL-1 translocated into the cytosol from LAMP-1+ endosomes. The artificial delivery of FSL-1 into the cytosol of B6BMMs drastically enhanced the IL-1ß production-inducing activity. FSL-1 as well as the representative NLRP3 inflammasome activator nigericin induced the NLRP3/ASC speck, but FSL-1 located in a compartment different from the NLRP3/ASC speck.

Phylogenetic and phylodynamic analyses of hepatitis C virus subtype 1a in Okinawa, Japan.

Okinawa Island, located in Southern Japan, has a higher prevalence rate of hepatitis C virus subtype 1a (HCV-1a) infection than that in mainland Japan. Okinawa has a history of US military occupation after World War II. To elucidate the transmission history of HCV-1a in Okinawa, 26 whole-genome sequences were obtained from 29 patients during 2011-2016. Phylogenetic trees were reconstructed to identify the origin and characteristics of HCV-1a in Okinawa with epidemiological information. A phylogenetic tree based on whole-genome sequencing revealed that all of the samples were located below the US branches. Additionally, we identified one cluster comprised of 17 strains (Okinawa, n = 16; United States, n = 1). The majority of the patients in this cluster were people who inject drugs (PWID), indicating the presence of a people who inject drugs (PWID) cluster. Subsequently, Bayesian analyses were employed to reveal viral population dynamics. Intriguingly, a phylodynamic analysis uncovered a substantial increase in effective population size of HCV-1a from 1965 to 1980 and a slight increase in mid-2000, which were associated with an increase in illicit drug use in Okinawa. The estimated divergence time of the PWID cluster was 1967.6 (1964.2-1971.1). These findings suggest that HCV-1a was introduced into Okinawa from the United States in the late 1960s, coincident with the Vietnam War. Subsequently, HCV-1a might have spread among the Japanese population with the spread of injecting drug use. Our study provides an understanding of HCV transmission dynamics in Okinawa, as well as the key role of PWID in HCV transmission.

Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.

Antiobesity effect of Pediococcus pentosaceus LP28 on overweight subjects: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: The population of the obese is increasing worldwide. Prevention and improvement of obesity are indispensable for decreasing the risk of metabolic disorders. We have recently shown that obesity and fatty liver are reduced by a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), in high-fat diet-induced obese mice. The aim of the present clinical study is to prove that LP28 is effective for reducing body fat and body weight, as shown in the experiment using mice. SUBJECTS/METHODS: The clinical trial was carried out as a double-blind, randomized, placebo-controlled study comprising 62 subjects (20-70 years of age, BMI 25-30 kg/m(2)). These subjects were randomly assigned to three groups that received living LP28, heat-killed LP28 or a placebo powder, administered orally once a day for 12 weeks. RESULTS: Heat-killed LP28 reduced BMI (0.45 kg/m(2), 95% CI (0.04, 0.86), P=0.035), body fat percentage (1.11%, (0.39, 1.82), P=0.002), body fat mass (1.17 kg (0.43, 1.92), P=0.004) and waist circumference (2.84 cm (0.74, 4.93), P=0.009) when compared with a placebo group. Fasting plasma glucose, HbA1c, fasting insulin, HOMA-IR and serum lipids levels did not change by either living LP28 or heat-killed LP28 intake. CONCLUSIONS: Heat-killed LP28 displays an antiobesity effect that reduces BMI, body fat and waist circumference, suggesting that the plant-derived lactic acid bacterium LP28 would be a promising preventive of metabolic syndrome.

Activation of inflammasomes in dendritic cells and macrophages by Mycoplasma salivarium.

Interleukin-1ß (IL-1ß) plays crucial roles in the pathogenesis of periodontal disease. It is produced after the processing of pro-IL-1ß by caspase-1, which is activated by the inflammasome-a multiprotein complex comprising nucleotide-binding domain leucine-rich repeat-containing receptor (NLR), the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and procaspase-1. Mycoplasma salivarium preferentially inhabits the gingival sulcus and the incidence and number of organisms in the oral cavity increase significantly with the progression of periodontal disease. To initially clarify the association of this organism with periodontal diseases, this study determined whether it induces IL-1ß production by innate immune cells such as dendritic cells or macrophages by using Mycoplasma pneumoniae as a positive control. Both live and heat-killed M. salivarium and M. pneumoniae cells induced IL-1ß production by XS106 murine dendritic cells as well as pyroptosis. The activities were significantly downregulated by silencing of caspase-1. Bone-marrow-derived macrophage (BMMs) from wild-type and NLR-containing protein 3 (NLRP3)-, ASC-, and caspase-1-deficient mice were examined for IL-1ß production in response to these mycoplasmas. Live M. salivarium and M. pneumoniae cells almost completely lost the ability to induce IL-1ß production by BMMs from ASC- and caspase-1-deficient mice. Their activities toward BMMs from NLRP3-deficient mice were significantly but not completely attenuated. These results suggest that live M. salivarium and M. pneumoniae cells can activate several types of inflammasomes including the NLRP3 inflammasome. Both M. salivarium and M. pneumoniae cells can activate THP-1 human monocytic cells to induce IL-1ß production. Hence, the present finding that M. salivarium induces IL-1ß production by dendritic cells and macrophages may suggest the association of this organism with periodontal diseases.

Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals.

Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.

Expression of microRNA-155 correlates positively with the expression of Toll-like receptor 7 and modulates hepatitis B virus via C/EBP-ß in hepatocytes.

Effective recognition of viral infection and successive activation of antiviral innate immune responses are vital for host antiviral defence, which largely depends on multiple regulators, including Toll-like receptors (TLRs) and microRNAs. Several early reports suggest that specific TLR-mediated immune responses can control hepatitis B virus (HBV) replication and express differentially with disease outcome. Considering the versatile function of miR-155 in the TLR-mediated innate immune response, we aimed to study the association between miR-155 and TLRs and their subsequent impact on HBV replication using both a HBV-replicating stable cell line (HepG2.2.15) and HBV-infected liver biopsy and serum samples. Our results showed that miR-155 was suppressed during HBV infection and a subsequent positive correlation of miR-155 with TLR7 activation was noted. Further, ectopic expression of miR-155 in vitro reduced HBV load as evidenced from reduced viral DNA, mRNA and subsequently reduced level of secreted viral antigens (HBsAg and HBeAg). Our results further suggested that CCAAT/enhancer-binding protein-ß (C/EBP-ß), a positive regulator of HBV transcription, was inhibited by miR-155. Taken together, our study established a correlation between miR-155 and TLR7 during HBV infection and also demonstrated in vitro that increased miR-155 level could help to reduce HBV viral load by targeting C/EBP-ß.

Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a nationwide survey.

PURPOSE: Intestinal neuronal dysplasia Type B (IND-B) has been proposed to be an allied disorder of Hirschsprung's disease (ADHD). The original histological criteria included hyperganglionosis, giant ganglia, ectopic ganglion cells and an increased AChE activity in the lamina propria. The criteria for IND-B have been gradually revised. The present diagnostic criteria are [1] more than 20 % of the submucosal ganglia contain nine or more ganglion cells and [2] the patient is older than 1 year. To clarify the current status of IND-B in Japan, a nationwide retrospective cohort study was performed. METHODS: Questionnaires were sent to 161 major institutes of pediatric surgery and gastroenterology in Japan. RESULTS: A total of 355 cases of ADHD were collected, including 18 cases of IND-B (5 %). Based on original criteria, 13 out of 18 cases were diagnosed as IND-B. However, only four cases met the current criteria. Three of the four patients (75 %) required pull-through operation. All of the patients exhibited giant ganglia and ganglioneuromatosis-like hyperplasia of the myenteric plexus. CONCLUSIONS: IND-B cases matching the current criteria are thought to be quite rare and they are associated with marked hyperplasia of the myenteric plexus. "True" IND-B is a rare and intractable disease.

Physical impairment and walking function required for community ambulation in patients with cervical incomplete spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To identify the physical impairments and walking function required for community ambulation in patients with cervical incomplete spinal cord injury (ISCI). SETTING: Chubu Rosai Hospital, Nagoya, Japan. METHODS: Forty patients with cervical ISCI (mean age: 49.9 years, American Spinal Injury Association Impairment Scale D) were included. The primary outcome measure was community ambulation based on Spinal Cord Independence Measure outdoor scores for a distance of >480 m. We measured the upper- and lower-extremity motor scores (UEMS and LEMS), sensory and spasticity. The walking tests included 10 m of walking at a comfortable- and maximum-walking speed (CWS and MWS; m s(-1)), 6 min walking test (6 MWT; m) and the walking index for spinal cord injury II (WISCI II). Multivariate logistic regression models were used to assess the physical impairments associated with community ambulation. Receiver operating characteristic curves were analyzed to determine the cutoff points for physical impairment and walking function. RESULT: The LEMS (beta coefficient (ß)=0.71) and UEMS (ß=0.41) were independently associated with community ambulation in patients with cervical ISCI. The cutoff points of the LEMS, UEMS, CWS, MWS, 6MWT and WISCI II were 41.5, 36.5, 1.00 m s(-1), 1.32 m s(-1), 472.5 m and 17.5, respectively, which suggests moderate to high accuracy. CONCLUSION: The LEMS and UEMS were the most important factors affecting community ambulation in patients with cervical ISCI. The cutoff points of the walking function tests were highly accurate; therefore, these points can serve as targets for walking training in the future.

Metabolic features of rats resistant to a high-fat diet.

OBJECTIVE: We assessed the metabolic characteristics of high-fat-diet-resistant (DR) rats. METHODS: Body weight, energy intake, locomotor activity, oxygen consumption, plasma leptin and lipid levels, size of visceral-fat adipocytes, and mRNA levels of genes related to lipid metabolism were measured in control rats fed standard chow and in obesity-prone (high-fat-diet-induced obesity, DIO) and DR rats fed a high-fat diet. Glucose tolerance and insulin tolerance tests were also performed. RESULTS: DIO rats gained weight more rapidly than did DR and control rats; DR rats gained less weight than did DIO rats despite similar energy intake. Energy expenditure did not differ among the three groups. The diameter of visceral-fat adipocytes was similar in DR and control rats. mRNA levels of genes involved in lipogenesis, such as fatty acid synthase and acetyl-CoA carboxylase, tended to be lower in DR than in control and DIO rats, whereas those of carnitine palmitoyltransferase 1a, which is involved in fatty acid ß-oxidation, were greater in DR rats than in the other groups. DIO rats showed hyperinsulinemia and glucose intolerance, whereas DR rats had high sensitivity to insulin. CONCLUSION: DR rats show suppression of lipogenesis and acceleration of fatty acid ß-oxidation in the visceral fat. These characteristics likely contribute to the anti-obesity phenotype of DR rats.