Subatomic structure of orthorhombic thaumatin at 0.89 Å reveals that highly flexible conformations are crucial for thaumatin sweetness.

Thaumatin is a sweet-tasting protein that elicits a sweet taste at a threshold of approximately 50 nM. Structure-sweetness relationships in thaumatin suggest that the basicity of two amino acids residues, Arg82 and Lys67, are particularly responsible for sweetness. Using tetragonal crystals, our structural analysis suggested that flexible sidechain conformations of these two residues play an important role in sweetness. However, in tetragonal crystals, Arg82 is adjacent to symmetry-related residues, and its flexibility is relatively restrained by the crystal packing. To reduce and diminish these symmetry-related effects, orthorhombic crystals were prepared, and their structures were successfully determined at a resolution of 0.89 Å. Within the orthorhombic lattice, two alternative conformations were more clearly visible at Lys67 than in a tetragonal system. Interestingly, for the first time, three alternative conformations at Arg82 were only found in an orthorhombic system. These results suggest the importance of flexible conformations in sweetness determinants. Such subtle structural variations might serve to adjust the complementarity of the electrostatic potentials of sweet receptors, thereby eliciting the potent sweet taste of thaumatin.

Binding Interaction Between Lauric Acid and Cluster of Differentiation 36 Underpinned by a Fluorescence- Intensifying Assay.

Cluster of differentiation 36 (CD36) is a scavenger receptor expressed in various vertebrate cells that contains diverse ligands, including long-chain fatty acids. This receptor has recently been suggested as a captor of specific volatile odorants (e.g., aliphatic acetates) in the mammalian nasal epithelium. This study used a fluorescence-intensifying assay to produce the first evidence that lauric acid, an odorous fatty acid, directly binds to CD36. This expansion of the repertoire of volatile ligands supports potential applications for nasal CD36. Our present findings could promote future research aimed at understanding the mechanisms of fatty acid interactions with CD36.

Dynamical modeling the effect of glucagon-like peptide on glucose-insulin regulatory system based on mice experimental observation.

As an emerging global epidemic, type 2 diabetes mellitus (T2DM) represents one of the leading causes of morbidity and mortality worldwide. Existing evidences demonstrated that glucagon-like peptide-1 (GLP-1) modulate the glucose regulatory system by enhancing the ß-cell function. However, the detailed process of GLP-1 in glycaemic regulator for T2DM remains to be clarified. Thus, in this study, we propose an Institute of Cancer Research (ICR) mice high fat and cholesterol dietary experimental data-driven mathematical model to investigate the secretory effect of GLP-1 on the dynamics of glucose-insulin regulatory system. Specifically, we develop a mathematical model of GLP-1 dynamics as part of the interaction model of ß-cell, insulin, and glucose dynamics. The parameter estimation and data fitting are in agreement with the data in mice experiments In addition, uncertainty quantification is performed to explore the possible factors that influence the pathways leading to the pathological state. Model analyses reveal that the high fat or high cholesterol diet stimulated GLP-1 plays an important role in the dynamics of glucose, insulin and ß cells in short-term. These results show that enhanced GLP-1 may mitigate the dysregulation of glucose-insulin regulatory system via promoting the ß cells function and stimulating secretion of insulin, which offers an in-depth insights into the mechanistic of hyperglycemia from dynamical approach and provide the theoretical basis for GLP-1 served as a potential clinical targeted drug for treatment of T2DM.

Associations between dairy consumption and the physical function in Japanese community-dwelling older adults: The Shimane CoHRE study.

OBJECTIVES: We investigated sex differences in the associations between dairy consumption and the physical function among community-dwelling older adults. METHODS: Six hundred and fifty-six older adults (75.6 ± 6.4 years old) participated in this study. Dairy consumption (5-item Likert score) and the physical function (gait speed, handgrip strength, and skeletal muscle mass) were measured. The linear and quadratic associations between dairy consumption and the physical function measures were examined by a multiple linear regression analysis adjusted for covariates. RESULTS: Among women, an increased dairy consumption was significantly linearly associated with greater hand-grip strength and faster gait speed (both p<0.05) after adjusting for covariates. Among men, dairy consumption was not associated with the physical function measures. Dairy consumption was not associated with the muscle mass in either sex. CONCLUSIONS: Increased dairy consumption was associated with a superior physical function in older women.

Quantitative Techniques of Ultrasonography in the Assessment of Femoropopliteal Atherosclerotic Lesions Using Peak Systolic Velocity Ratio: Results From the TURN-UP Study.

PURPOSE: Duplex ultrasound (DUS)-measured peak systolic velocity ratios (PSVRs) are commonly used to evaluate arterial stenosis in lower extremity artery disease (LEAD). However, these measurement methods have not yet been standardized. This study aimed to reveal the influence of measuring methods on PSVR values. METHODS: A 132 femoropopliteal lesions with PSVR ranging from 1.5 to 3.5 evaluated using method A (angle correction 60°, the direction of blood flow, the no or few atherosclerotic changes closest to the lesion proximal side was defined as the nonstenotic area) were included. The following 4 different methods were then compared with method A: method B, angle correction 45°; method C, angle correction 60° measured along the vessel wall; D, angle correction 60°, with the nonstenotic area the lowest peak systolic velocity area; and E, angle correction 60°, with the reference point fixed at 2 cm proximal to the target lesion area. The difference in PSVR values was analyzed using the Bland-Altman method. RESULTS: The mean PSVR value measured by method A was 2.27±0.51, those measured by methods B, C, D, and E were 2.21±0.55, 2.31±0.66, 2.34±0.63, and 2.11±0.63, respectively. The 95% prediction intervals of the differences in PSVR measurements versus A were -0.64 to +0.53 for method B, -0.59 to +0.68 for method C, -0.77 to +0.91 for method D, and -1.12 to +0.79 for method E. CONCLUSION: PSVR values considerably differed between measuring methods. PSVR values by DUS are largely dependent on the measurement methods, which could considerably affect the judgment of LEAD. CLINICAL IMPACT: Due to differences in several DUS measurement methods, the PSVR results could be changed. Therefore, to need further investigations and unification of measurement method.

Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults.

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.

Esports for Seniors: Acute Effects of Esports Gaming in the Community on the Emotional State and Heart Rate among Japanese Older Adults.

In the last few years, esports have become popular among older individuals. Although participation in esports can become a novel activity for older adults, evidence on their effects is limited to young individuals. This study investigated the effects of esports participation on the emotional and physiological states of older adults. Twenty-five older men and women participating in health promotion activities in community centers (75 ± 8 years old) played a two-player racing game (Gran Turismo Sport, Sony) for 8-10 min. Their heart rates (HRs) were measured while the subjects played the games. The blood pressure (BP) and Profile of Mood States (POMS) were measured before and after gaming. The average HR during games (98 ± 17 bpm) was significantly higher than at pre-gaming (76 ± 11 bpm, p < 0.001). The BP before and after the games did not significantly change. Interestingly, the vigor scores (positive mood affect) in POMS increased after the games (p < 0.05) in females, but not in males. In summary, among older individuals, playing esports games showed a moderate increase in HR, no spike/drop of BP, and positive mood elevation. Our preliminary data suggest the feasibility of participating in esports in a community for older adults and that it could affect mood positively, especially among older women.

Associations between physical frailty and living arrangements in Japanese older adults living in a rural remote island: The Shimane CoHRE study.

Background: Living arrangements have been known to be associated with physical frailty. However, the prevalence of frailty and its risk factors in remote islands is not understood. We examined the association between living arrangements and objectively measured frailty among older adults living in a remote island of Japan. Methods: Among older people living in Okinoshima, 656 older adults (75.6 ± 6.4 years) were analyzed. Physical frailty (robust, prefrailty, or frailty) was assessed using the 5-item frailty phenotype (unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity). Physical functions (muscle mass, gait speed, and grip strength) were measured objectively. Results: The prevalence of frailty and prefrailty was 6.6% and 43.8%, respectively. Living with a spouse resulted in a significantly lower prevalence of frailty (p < 0.001) compared with other living arrangements. All objectively measured physical functions among those who lived with a spouse were significantly superior to those who lived with family or alone (p < 0.001). Multinomial logistic regression showed that living alone was significantly associated with frailty (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.07-5.24) and prefrailty (OR 1.75, 95% CI 1.14-2.69) after adjusting for all covariates. Conclusion: The prevalence of frailty on remote islands seemed similar to that in urban areas. Older people living in remote islands might be able to maintain their physical health. Furthermore, living alone may correlate with increased risks of frailty and prefrailty. Among elderly individuals on remote islands, living with a spouse might be desirable to prevent (pre)frailty.

Structure of thaumatin under acidic conditions: Structural insight into the conformations in lysine residues responsible for maintaining the sweetness after heat-treatment.

Thaumatin is an intensely sweet-tasting protein. Its sweetness persists when heated under acidic conditions, but disappears when heated at a pH above 7.0. To clarify how the structural features of thaumatin resist insoluble aggregation during heating under acidic conditions, we analysed its crystal structure obtained at pH 4.0, 6.0, and 8.0. Simultaneously, the melting temperature (Tm) at these pH levels was determined using differential scanning fluorimetry. At pH 4.0, the Tm of thaumatin was substantially lower and the overall B-factor value of its structure was higher than those at pH 6.0. Interestingly, the relative B-factor values for most lysine residues decreased as the pH reduced. These results suggest that the overall structure at pH 4.0 becomes flexible but the relative flexibility of some regions is lower than that at pH 6.0. Thus, the reduction in relative flexibility might play an important role in preventing thermal aggregation, thereby maintaining the sweetness.

Combined association of oral and skeletal muscle health with type 2 diabetes mellitus among community-dwelling older adults in Japan: a cross-sectional study.

Objective: Although oral health and skeletal muscle status are known to be risk factors for type 2 diabetes mellitus (T2DM), there is limited information on their combined effects among community-dwelling older adults. The purpose of this study was to investigate the association between oral health and skeletal muscle status among older adults with T2DM in Japan. Participants and Methods: This cross-sectional study included data from individuals aged ≥60 years. T2DM was defined as a glycosylated hemoglobin A1c level ≥48 mmol/mol (≥6.5%) or the use of hypoglycemic agents. For oral health status, dental hygienists assessed the number of teeth (NT) and masticatory function (MF). Skeletal muscle status was assessed using skeletal muscle mass index (SMI) and handgrip strength (HGS). Logistic regression analysis examined T2DM in nine-category combinations of oral health status (each of the three categories in NT and MF) and skeletal status (each of the three categories in SMI and HGS). Results: T2DM was prevalent in 83 participants (16.4%) and was significantly associated with low NT and SMI (odds ratio [OR] = 5.93, 95% confidence interval [CI]: 1.37-25.73) and low MF and SMI (OR = 4.48, 95% CI: 1.23-16.35) compared to high NT and SMI and high MF and SMI, respectively. Conclusion: Our findings indicate that low muscle mass with tooth loss or masticatory dysfunction is associated with T2DM among community-dwelling older adults. This suggests that maintaining oral health and muscle mass may be an effective strategy for the prevention of T2DM.

Assessment of direct binding interaction between CD36 and its potential lipid ligands using a peptide mimic of the receptor labeled with a fluorophore.

Cluster of differentiation 36 (CD36) is a cell-surface receptor that recognizes diverse substances. We have presented indirect evidence that a short segment of the receptor comprising amino acids 149-168 contains a site for binding of its lipid ligands (e.g., distinct fatty acids and aldehydes). However, experimental support for their direct interactions is yet to be achieved. For this, we devised a fluorescence intensity assay, where a synthetic peptide consisting of CD36 amino acids 149-168 labeled with fluorescein isothiocyanate (FITC-CD36149-168) and its variant peptides were used as positive and negative probes, respectively. First, we obtained results indicating that 1-palmitoyl-2-(5-keto-6-octenedioyl)phosphatidylcholine (an established CD36 ligand) but not 1-palmitoyl-2-arachidonyl-phosphatidylcholine (a non-ligand of the receptor) bound in a saturable and specific manner to FITC-CD36149-168. Strikingly, the assay allowed us to provide the first evidence supporting direct and specific binding between the CD36 segment and fatty aldehydes (e.g., Z-11-hexadecenal). However, this method failed to illustrate specific interactions of the segment with fatty acids, such as oleic acid. Nonetheless, our findings offer further insight into the biologically relevant ligands and the role of CD36. In addition, we suggest that this fluorescence-based technique provides a convenient means to evaluate protein (peptide)-lipid interactions.

Effect of Multimorbidity on Fragility Fractures in Community-Dwelling Older Adults: Shimane CoHRE Study.

Fragility fractures (FFxs), which are a common musculoskeletal injury in older adults, is associated with an increased frequency of falls. Both FFxs and falls may result from drugs, habits, and co-occurring diseases. We aimed to evaluate the effects of various diseases on the risk of FFx. This retrospective study included 1420 individuals aged ≥60 years. We evaluated the history of clinical FFx and diseases using a detailed questionnaire and a health examination. The risk of comorbidities was assessed using the Age-Adjusted Charlson Comorbidity (AAC) Index. We performed binary logistic regression analysis to determine the risk of FFx and falls after adjusting for covariates. In elderly men, the incidence of FFx positively correlated with rheumatoid arthritis and parent's hip fracture. For elderly women, the incidence of FFx positively correlated with rheumatoid arthritis and antihypertensive drugs but was inversely associated with dyslipidemia and antilipidemic drugs. The FFX risk of older adults with an AAC Index ≥6 was higher than those with an AAC Index of 1-3. In addition, the AAC Index and falls were independently and strongly associated with a higher risk of FFx. Taken together, multimorbidity increases the risk of clinical FFx independent of falls in the community-dwelling elderly population.

Number of teeth and masticatory function are associated with sarcopenia and diabetes mellitus status among community-dwelling older adults: A Shimane CoHRE study.

OBJECTIVES: We aimed to examine the number of teeth and masticatory function as oral health indices and clarify their roles in the pathogenesis of sarcopenia and diabetes mellitus in community-dwelling older adults. SUBJECTS AND METHODS: This cross-sectional study was conducted with 635 older adults in Ohnan, Shimane Prefecture, in rural Japan. The number of teeth and masticatory function (measured by the number of gummy jelly pieces collected after chewing) were evaluated by dental hygienists. Sarcopenia status was assessed using handgrip strength, skeletal muscle index, calf circumference, and a possible sarcopenia diagnosis based on the Asian Working Group for Sarcopenia 2019. Diabetes mellitus status was defined as a hemoglobin A1c level ≥6.5% or self-reported diabetes. A multivariable logistic regression model was used to analyze the association between oral health, sarcopenia, and diabetes mellitus after adjusting for confounders. RESULTS: After adjusting for all confounders, logistic regression analysis showed that the number of remaining teeth was negatively associated with a low level of handgrip strength (odds ratio [OR], 0.961; 95% confidence interval [CI], 0.932-0.992) and possible sarcopenia (OR, 0.949; 95% CI, 0.907-0.992). Higher levels of masticatory function were also negatively associated with a low level of handgrip strength (OR, 0.965; 95% CI, 0.941-0.990) and possible sarcopenia (OR, 0.941; 95% CI, 0.904-0.979). Logistic regression analysis showed that the number of remaining teeth and a higher level of masticatory function were negatively associated with diabetes mellitus (OR, 0.978; 95% CI, 0.957-0.999; OR, 0.976; 95% CI, 0.960-0.992, respectively). CONCLUSION: Our findings suggest that improvement in oral health, including the maintenance of masticatory function and remaining teeth, may contribute to the prevention of sarcopenia and diabetes mellitus in older adults.

Assessing the Impact of a Hilly Environment on Depressive Symptoms among Community-Dwelling Older Adults in Japan: A Cross-Sectional Study.

Although some neighborhood environmental factors have been found to affect depressive symptoms, few studies have focused on the impact of living in a hilly environment, i.e., land slope, on depressive symptoms among rural older adults. This cross-sectional study aimed to investigate whether a land slope is associated with depressive symptoms among older adults living in rural areas. Data were collected from 935 participants, aged 65 years and older, who lived in Shimane prefecture, Japan. Depressive symptoms were assessed using the Zung Self-Rating Depression Scale (SDS) and defined on the basis of an SDS score ≥ 40. Land slopes within a 400 m network buffer were assessed using geographic information systems. Odds ratios (ORs) with 95% confidence intervals (CIs) of depressive symptoms were estimated using logistic regression. A total of 215 (23.0%) participants reported depressive symptoms. The land slope was positively associated with depressive symptoms (OR = 1.04; 95% CI = 1.01-1.08) after adjusting for all confounders. In a rural setting, living in a hillier environment was associated with depressive symptoms among community-dwelling older adults in Japan.

Inconvenience of Living Place Affects Individual HbA1c Level in a Rural Area in Japan: Shimane CoHRE Study.

BACKGROUND: It has been shown that the socio-geographical environment of residential areas, such as altitude, affects the health status and health-maintenance behavior of residents. Here, we examined a hypothesis that altitude of residence would influence glycemic control in a general elderly population living in a rural area. METHODS: A thousand and sixteen participants living in a mountainous region in Japan were recruited at health examinations. Hemoglobin A1c (HbA1c) was measured in serum as a parameter of glycemic control. The altitude of residence, distance to grocery stores and to medical facilities were estimated using a geographic information system. RESULTS: Linear regression analysis confirmed a significant effect of the altitude on log HbA1c even after adjustment of other demographic and biochemical factors. When the distance to grocery stores or medical facilities were used instead of the altitude in a linear regression analysis, distance to secondary medical facilities alone showed a significant effect on HbA1c. CONCLUSIONS: We found a positive correlation between HbA1c level and residential altitude in a rural area of Japan. The altitude seemed to be a parameter substituting the inconvenicence of residential areas. Socio-geographical factors of living place, such as inconvenience, may influence glycemic control of the residents.

Prevalence of lifestyle-related chronic diseases among agricultural and non-agricultural workers in ruralareas of Japan: the Shimane CoHRE study.

Objective: Engaging in agriculture greatly affects workers' lifestyles, particularly related to physical activity. This study aimed to clarify the prevalence of lifestyle-related chronic diseases among workers engaging and not engaging in agriculture in rural areas of Japan. Methods: A total of 4,666 consecutive participants aged ≥40 years (1,929 men and 2,737 women) were recruited during health examinations conducted from 2006 to 2014. For analysis, the participants were divided by sex and age into those engaging in agriculture and those not engaging in agriculture. Results: Engaging in agriculture may be contributing with a low prevalence of dyslipidemia, a constitutive factor of metabolic syndrome, in both sexes between the ages of 40 and 64 years. In the elderly aged ≥65 years, engaging in agriculture may influence the low prevalence of hypertension in men. Hypertension, a strong risk factor for stroke and cardiovascular disease, is very frequent among the Japanese elderly and, therefore, engaging in agriculture may have a significant impact on its prevention and control. Conclusion: In rural areas of Japan, engaging in agriculture may contribute to the control of lipid metabolism in middle-aged individuals and blood pressure in the elderly.

Height loss but not body composition is related to low back pain in community-dwelling elderlies: Shimane CoHRE study.

BACKGROUND: Low back pain (LBP) is a common complaint in the elderly Japanese population. Although previous studies showed that height loss was associated with LBP, it remains unclear whether LBP is associated with body composition. The objective of the present study was to investigate whether body composition and physical characteristics, including height loss, were associated with LBP. METHODS: The present study is retrospectively registered, and the participants were 2212 community-dwelling Japanese people aged over 60 years who participated in the Shimane CoHRE study in 2016. We investigated the presence of LBP, body composition parameters (muscle, fat, body weight, and bone mass), physical characteristics (body height and height loss), chronic diseases, history of fall, smoking, and drinking habits. We examined the relationships of body composition parameters and physical characteristics with point prevalence of LBP using multivariate logistic regression. RESULTS: The point prevalence of LBP was 43.2% in women and 39.5% in men. Logistic regression models showed that body height and body composition were not significantly associated with LBP; however, height loss was associated significantly with LBP in women and men (OR: 1.14, 95% CI: 1.08-1.20 and OR: 1.13, 95% CI: 1.06-1.21, respectively). Hypertension (OR: 1.32, 9 5% CI: 1.04-1.69) and chronic heart disease (OR: 1.57, 95% CI: 1.01-2.43) in women and history of fall (OR: 1.70, 95% CI: 1.13-2.56) and cerebrovascular disease (OR: 1.88, 95% CI: 1.05-3.34) in men were significantly associated with LBP. However, body composition was not associated with LBP in either gender. CONCLUSIONS: The present study demonstrated that height loss, but not body composition, was related to LBP in community-dwelling elderly people. To elucidate the cause of LBP, it is important to consider the relationship with height loss.

Additive Effect of Physical Activity and Sedentary Time on Depressive Symptoms in Rural Japanese Adults: A Cross-Sectional Study.

BACKGROUND: Previous studies have reported an additive effect of moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) on depressive symptoms. However, no studies have been conducted in rural community settings. This cross-sectional study investigated whether the additive effect of MVPA and ST was associated with depressive symptoms in rural Japanese adults. METHODS: We identified 2,814 participants from health examinations conducted in Shimane, rural Japan, in 2012 and analyzed data from 1,958 participants. We assessed depressive symptoms using the Zung Self-Rating Depression Scale and measured the total time spent on MVPA and ST using a Japanese short version of the International Physical Activity Questionnaire. Poisson regression analysis examined the prevalence ratios (PR) of depressive symptoms in nine category combinations of MVPA level (no, insufficient, or sufficient MVPA) and ST level (high, moderate, or low ST). RESULTS: A total of 117 (6.0%) participants had depressive symptoms. Compared with the reference category (no MVPA/high ST), multivariate analysis showed that the likelihood of depressive symptoms was significantly lower in the sufficient MVPA/low ST category (PR 0.23; 95% confidence intervals [CI], 0.08-0.66), insufficient MVPA/low ST category (PR 0.37; 95% CI, 0.16-0.86), and insufficient MVPA/moderate ST category (PR 0.39; 95% CI, 0.17-0.90). CONCLUSION: Analysis of the additive effect of MVPA and ST showed that the combinational category of sufficient MVPA and low ST had the lowest prevalence of depressive symptoms in rural Japanese adults. Moderate ST and low ST showed significantly lower likelihoods of depressive symptoms, regardless of insufficient MVPA.

Association of High-Density Lipoprotein Subclasses with Carotid Intima-Media Thickness: Shimane CoHRE Study.

AIMS: Recent studies suggested that subclasses of high-density lipoprotein (HDL) may be a better biomarker to predict the risk of atherosclerotic disorders. We aimed to examine the association of HDL2- and HDL3-cholesterol (HDL2-C and HDL3-C) with carotid intima-media thickness (IMT) using a new method to quantify the HDL-C subclasses. METHODS: Participants were 657 Japanese subjects (434 women) who received a health examination (mean age: 73 years). Serum samples were analyzed by the homogenous assay for HDL-C and HDL3-C. HDL2-C was calculated indirectly by subtracting HDL3-C from HDL-C. HDL3-C measured by this assay was well correlated with that measured by ultracentrifugation (r=0.898, p＜0.001). The maximum IMT (max-IMT) and plaque score (PS) were evaluated by ultrasonography following the standard protocol. RESULTS: HDL3-C was associated with age both in men (r=－0.322, p＜0.0001) and women (r=－0.315, p＜0.0001). In a simple regression analysis, max-IMT showed an inverse association with HDL3-C, whereas no significant association was observed with HDL2-C. A multiple linear regression analysis indicated, however, that the association between HDL3-C and max-IMT was not significant in both aged and younger populations when age was included in the analysis. Further, not only HDL2-C but also HDL3-C was not a significant predictor of 'atherosclerotic arteries' defined as the max-IMT ≥1.5 mm. Similar results were observed in the analysis on PS. CONCLUSIONS: Neither HDL3-C nor HDL2-C was significantly associated with carotid atherosclerosis in the Japanese population in this study.