A Community-Based Intervention to Enhance Subjective Well-Being in Older Adults: Study Design and Baseline Participant Profiles.

Promoting subjective well-being is a crucial challenge in aging societies. In 2022, we launched a community-based intervention trial (the Chofu-Digital-Choju Movement). This initiative centered on fostering in-person and online social connections to enhance the subjective well-being of older adults. This paper describes the study design and baseline survey. This quasi-experimental study involved community-dwelling older adults aged 65-84 years in Chofu City, Tokyo, Japan. A self-administered questionnaire was distributed to 3742 residents (1681 men and 2061 women), and a baseline survey was conducted in January 2022. We assessed subjective well-being (primary outcome); psychosocial, physical, and dietary factors; and the use of information and communication technology variables (secondary outcomes) among the participants. After the intervention involving online classes, community hubs, and community events, a 2-year follow-up survey will be conducted to evaluate the effects of the intervention, comparing the intervention group (participants) with the control group (non-participants). We received 2503 questionnaires (66.9% response rate); of these, the analysis included 2343 questionnaires (62.6% valid response rate; mean age, 74.4 (standard deviation, 5.4) years; 43.7% male). The mean subjective well-being score was 7.2 (standard deviation, 1.9). This study will contribute to the development of a prototype subjective well-being strategy for older adults.

Antiphase synchrony increases perceived entitativity and uniqueness: A joint hand-clapping task.

In- and antiphase are the dominant patterns identified in the study of synchrony in relative phases. Many previous studies have focused on in-phase synchrony and compared it to asynchrony, but antiphase synchrony has yet not been the subject of much research attention. The limited findings on antiphase synchrony suggest that its role or nature is unclear or unstable in human interaction. To account for this factor, this study examined the possibility that antiphase synchrony simultaneously induced perceived entitativity and uniqueness. The results of an experiment employing a joint hand-clapping task supported this prediction. Further, the elevated feeling of uniqueness in those who experienced antiphase synchrony may have increased the self-other overlap for those who felt oneness with their partner, but it decreased overlap for those who did not. The theoretical implications for synchrony literature are discussed.

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states.

Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity.

Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle.

Systemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (ob/ob) mice, identifying components with differential abundance and differential regulation in ob/ob mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and ob/ob mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.

Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis.

Hepatic fat accumulation is associated with diabetes and hepatocellular carcinoma (HCC). Here, we characterize the metabolic response that high-fat availability elicits in livers before disease development. After a short term on a high-fat diet (HFD), otherwise healthy mice showed elevated hepatic glucose uptake and increased glucose contribution to serine and pyruvate carboxylase activity compared with control diet (CD) mice. This glucose phenotype occurred independently from transcriptional or proteomic programming, which identifies increased peroxisomal and lipid metabolism pathways. HFD-fed mice exhibited increased lactate production when challenged with glucose. Consistently, administration of an oral glucose bolus to healthy individuals revealed a correlation between waist circumference and lactate secretion in a human cohort. In vitro, palmitate exposure stimulated production of reactive oxygen species and subsequent glucose uptake and lactate secretion in hepatocytes and liver cancer cells. Furthermore, HFD enhanced the formation of HCC compared with CD in mice exposed to a hepatic carcinogen. Regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism to those identified in fat exposed nontransformed mouse livers, however, particular lipid species were elevated in HFD tumor and nontumor-bearing HFD liver tissue. These findings suggest that fat can induce glucose-mediated metabolic changes in nontransformed liver cells similar to those found in HCC. SIGNIFICANCE: With obesity-induced hepatocellular carcinoma on a rising trend, this study shows in normal, nontransformed livers that fat induces glucose metabolism similar to an oncogenic transformation.

Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity.

Impaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in healthy and obese states, we constructed and analyzed transomics glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multiomics time course data from wild-type and leptin-deficient obese (ob/ob) mice after orally administered glucose. In wild-type mice, metabolic reactions were rapidly regulated within 10 min of oral glucose administration by glucose-responsive metabolites, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-induced changes in the expression of glucose-responsive genes encoding metabolic enzymes. In ob/ob mice, the majority of rapid regulation by glucose-responsive metabolites was absent. Instead, glucose administration produced slow changes in the expression of carbohydrate, lipid, and amino acid metabolic enzyme-encoding genes to alter metabolic reactions on a time scale of hours. Few regulatory events occurred in both healthy and obese mice. Thus, our transomics network analysis revealed that regulation of glucose-responsive liver metabolism is mediated through different mechanisms in healthy and obese states. Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, whereas slow changes in gene expression dominate the obese state.

Single-Cell Information Analysis Reveals That Skeletal Muscles Incorporate Cell-to-Cell Variability as Information Not Noise.

Cell-to-cell variability in signal transduction in biological systems is often considered noise. However, intercellular variation (i.e., cell-to-cell variability) has the potential to enable individual cells to encode different information. Here, we show that intercellular variation increases information transmission of skeletal muscle. We analyze the responses of multiple cultured myotubes or isolated skeletal muscle fibers as a multiple-cell channel composed of single-cell channels. We find that the multiple-cell channel, which incorporates intercellular variation as information, not noise, transmitted more information in the presence of intercellular variation than in the absence according to the "response diversity effect," increasing in the gradualness of dose response by summing the cell-to-cell variable dose responses. We quantify the information transmission of human facial muscle contraction during intraoperative neurophysiological monitoring and find that information transmission of muscle contraction is comparable to that of a multiple-cell channel. Thus, our data indicate that intercellular variation can increase the information capacity of tissues.

Lysophosphatidylethanolamine acyltransferase 2 (LPEAT2) incorporates DHA into phospholipids and has possible functions for fatty acid-induced cell death.

Glycerophospholipids, one of the main constituents of biological membranes, are synthesized from glycerol-3-phosphate through the de novo pathway, and are reconstituted through the remodeling pathway. Lysophosphatidylethanolamine acyltransferase 2 (LPEAT2), one of the enzymes that play a role in the remodeling pathway, has been previously reported to have LPEAT, lysophosphatidylcholine acyltransferase (LPCAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities with 16:0-CoA, 18:0-CoA, and 18:1-CoA as donors. In this study, we found that LPEAT2 is active with 22:6-CoA. Knockdown studies using Neuro 2A cells showed that LPEAT2 has endogenous LPEAT activity with 22:6-CoA, and that LPEAT2 has functions for modulating 22:6/20:4 ratios of phospholipids. In addition, we demonstrated that Neuro 2A cells overexpressing LPEAT2 underwent cell death with necrotic morphology when differentiated into neuron-like cells, with supplementation with 22:6 (DHA). These results suggest that LPEAT2 plays a role in inducing cell death DHA-dependently. This study will lead to better understand how DHA levels are regulated in phospholipids, especially in the brain where LPEAT2 is highly expressed. Our study also provides insight to understand the mechanism of cell death induced by DHA.

Characterization of the unique In Vitro effects of unsaturated fatty acids on the formation of amyloid ß fibrils.

Accumulation of amyloid ß (Aß) peptides, the major component of amyloid fibrils in senile plaques, is one of the main causes of Alzheimer's disease. Docosahexaenoic acid (DHA) is a fatty acid abundant in the brain, and is reported to have protective effects against Alzheimer's disease, although the mechanistic effects of DHA against Alzheimer's pathophysiology remain unclear. Because dietary supplementation of DHA in Aß precursor protein transgenic mice ameliorates Aß pathology and behavioral deficits, we hypothesize that DHA may affect the fibrillization and deposition of Aß. Here we studied the effect of different types of fatty acids on Aß fibril formation by in vitro Aß fibrillization assay. Formation of amyloid fibrils consists of two steps, i.e., the initial nucleation phase and the following elongation phase. We found that unsaturated fatty acids, especially DHA, accelerated the formation of Aß fibrils with a unique short and curved morphology in its nucleation phase, which did not elongate further into the long and straight, mature Aß fibrils. Addition of DHA afterwards did not modify the morphology of the mature Aß(1-40) fibrils. The short and curved Aß fibrils formed in the presence of DHA did not facilitate the elongation phase of Aß fibril formation, suggesting that DHA promotes the formation of "off-pathway" conformers of Aß. Our study unravels a possible mechanism of how DHA acts protectively against the pathophysiology of Alzheimer's disease.

Which cytokine is the most related to weight loss-induced decrease in arterial stiffness in overweight and obese men?

Obesity and increased arterial stiffness are risk factors for cardiovascular disease. A well-known characteristic of obesity is the chronic low-grade inflammatory state, and it causes elevation of arterial stiffness. Weight-loss reduces arterial stiffness and inflammatory level in obese individuals. However, it is unclear which inflammatory factor is most related to weight loss-induce decreases in arterial stiffness in overweight and obese men. Thus, the aim of this study was to determine which circulating cytokine level has the most effect on decreasing arterial stiffness after lifestyle modification. Twenty overweight and obese men completed a 12-week period of lifestyle modifications (combination of aerobic exercise training and dietary modification). We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness, and circulating cytokine levels using comprehensive analysis. After the 12-week lifestyle modifications, body mass was markedly decreased. Also, baPWV and the levels of several circulating cytokines significantly decreased after the lifestyle modifications. We observed a positive correlation between changes in baPWV and circulating interleukin-6 (IL-6) levels. Furthermore, multiple liner regression analysis revealed that change in baPWV was significantly associated with that in IL-6 levels after consideration of changes in systolic blood pressure and body mass index. These results suggest that for overweight and obese men, a 12-week period of lifestyle modifications-induced a decrease in circulating cytokine levels (especially IL-6 levels), leads to decreased baPWV.

Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport.

Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unknown. Here, we show that the lack of lysophosphatidylcholine acyltransferase 3 (LPCAT3) leads to drastic reductions in membrane arachidonate levels, and that LPCAT3-deficient mice are neonatally lethal due to an extensive triacylglycerol (TG) accumulation and dysfunction in enterocytes. We found that high levels of PUFAs in membranes enable TGs to locally cluster in high density, and that this clustering promotes efficient TG transfer. We propose a model of local arachidonate enrichment by LPCAT3 to generate a distinct pool of TG in membranes, which is required for normal directionality of TG transfer and lipoprotein assembly in the liver and enterocytes.

Lysophospholipid acyltransferases mediate phosphatidylcholine diversification to achieve the physical properties required in vivo.

The acyl-chain composition of the major mammalian phospholipid phosphatidylcholine (PC) is distinct in various tissues. Although it was classically suggested that PC diversity is acquired through acyl-chain remodeling, the mechanisms and biological relevance of acyl-chain diversity remain unclear. Here, we show that differences in the substrate selectivity of lysophospholipid acyltransferases regulate tissue PC acyl-chain composition through contribution of both the de novo and remodeling pathways, depending on the fatty acid species. Unexpectedly, while dipalmitoyl-PC (DPPC) is enriched through the remodeling pathway, several polyunsaturated PC molecules accumulate during the de novo pathway. We confirmed this concept for DPPC in pulmonary surfactant and showed that the biophysical properties of this lipid are important to prevent the early onset of acute lung injury. We propose a model of harmonized processes for phospholipid diversification to satisfy in vivo requirements, with an example of its biological relevance.

Low-volume, high-intensity, aerobic interval exercise for sedentary adults: VO2max, cardiac mass, and heart rate recovery.

PURPOSE: The aim of this study was to compare the effects of low-volume, high-intensity aerobic interval training (HAIT) on maximal oxygen consumption (VO2max), left ventricular (LV) mass, and heart rate recovery (HRR) with high-volume, moderate-intensity continuous aerobic training (CAT) in sedentary adults. METHODS: Twenty-four healthy but sedentary male adults (aged 29.2 ± 7.2 years) participated in an 8-week, 3-day a week, supervised exercise intervention. They were randomly assigned to either HAIT (18 min, 180 kcal per exercise session) or CAT (45 min, 360 kcal). VO2max, LV mass (3T-MRI), and HRR at 1 min (HRR-1) and 2 min (HRR-2) after maximal exercise were measured pre- and post-intervention. RESULTS: Changes in VO2max during the 8-week intervention were significant (P < 0.01) in both groups (HAIT, 8.7 ± 3.2 ml kg(-1) min(-1), 22.4 ± 8.9%; CAT, 5.5 ± 2.8 ml kg(-1) min(-1), 14.7 ± 9.5%), while the VO2max improvement in HAIT was greater (P = 0.02) than in CAT. LV mass in HAIT increased (5.1 ± 8.4 g, 5.7 ± 9.1%, P = 0.05), but not in CAT (0.9 ± 7.8 g, 1.1 ± 8.4%, P = 0.71). While changes in HRR-1 were not significant in either group, change in HRR-2 for HAIT (9.5 ± 6.4 bpm, 19.0 ± 16.0%, P < 0.01) was greater (P = 0.03) than for CAT (1.6 ± 10.9 bpm, 3.9 ± 16.2%, P = 0.42). CONCLUSIONS: This study suggests that HAIT has potential as a time-efficient training mode to improve cardiorespiratory capacity and autonomic nervous system function in sedentary adults.

Acceleration training for improving physical fitness and weight loss in obese women.

BACKGROUND: Reducing body weight and visceral adipose tissue (VAT) are the primary goals for maintaining health in obese individuals as compared to those of normal weight, but it is also important to maintain physical fitness for a healthy life after weight-loss. Acceleration training (AT) has recently been indicated as an alternative to resistance training for elite athletes and also as a component of preventive medicine. However, it is unclear whether combining AT with a weight-loss diet will improve physical fitness in obese individuals. The present study aimed to determine the synergistic effects of AT on body composition and physical fitness with weight-loss program in overweight and obese women. METHODS: Twenty-eight obese, middle-aged women were divided into two groups as follows: diet and aerobic exercise group (DA; BMI: 29.3 ± 3.0 kg/m2); and diet, aerobic exercise and acceleration training group (DAA; BMI: 31.2 ± 4.0 kg/m2). Both groups included a 12-week weight-loss program. Body composition, visceral adipose tissue (VAT) area and physical fitness (hand grip, side-to-side steps, single-leg balance with eyes closed, sit-and-reach and maximal oxygen uptake) were measured before and after the program. RESULT: Body weight, BMI, waist circumference and VAT area decreased significantly in both groups. Hand grip (2.1 ± 3.0 kg), single-leg balance (11.0 ± 15.4 s) and sit-and-reach (6.5 ± 4.8 cm) improved significantly only in the DAA group. CONCLUSIONS: Our findings indicate that combining AT with classical lifestyle modifications is effective at reducing VAT, and it may enhance muscle strength and performance in overweight and obese women.

A novel lysophosphatidic acid acyltransferase enzyme (LPAAT4) with a possible role for incorporating docosahexaenoic acid into brain glycerophospholipids.

Glycerophospholipids are important components of cellular membranes, required for constructing structural barriers, and for providing precursors of bioactive lipid mediators. Lysophosphatidic acid acyltransferases (LPAATs) are enzymes known to function in the de novo glycerophospholipid biosynthetic pathway (Kennedy pathway), using lysophosphatidic acid (LPA) and acyl-CoA to form phosphatidic acid (PA). Until now, three LPAATs (LPAAT1, 2, and 3) have been reported from the 1-acyl-glycerol-3-phosphate O-acyltransferase (AGPAT) family. In this study, we identified a fourth LPAAT enzyme, LPAAT4, previously known as an uncharacterized enzyme AGPAT4 (LPAATδ), from the AGPAT family. Although LPAAT4 was known to contain AGPAT motifs essential for acyltransferase activities, detailed biochemical properties were unknown. Here, we found that mouse LPAAT4 (mLPAAT4) possesses LPAAT activity with high acyl-CoA specificity for polyunsaturated fatty acyl-CoA, especially docosahexaenoyl-CoA (22:6-CoA, DHA-CoA). mLPAAT4 was distributed in many tissues, with relatively high expression in the brain, rich in docosahexaenoic acid (DHA, 22:6). mLPAAT4 siRNA in a neuronal cell line, Neuro 2A, caused a decrease in LPAAT activity with 22:6-CoA, suggesting that mLPAAT4 functions endogenously. siRNA in Neuro 2A cells caused a decrease in 18:0-22:6 PC, whereas mLPAAT4 overexpression in Chinese hamster ovary (CHO)-K1 cells caused an increase in this species. Although DHA is considered to have many important functions for the brain, the mechanism of its incorporation into glycerophospholipids is unknown. LPAAT4 might have a significant role for maintaining DHA in neural membranes. Identification of LPAAT4 will possibly contribute to understanding the regulation and the biological roles of DHA-containing glycerophospholipids in the brain.

Effects of lifestyle modification on central blood pressure in overweight and obese men.

OBJECTIVE: It has recently been recognized that increased central blood pressure is a predictor of cardiovascular disease. Central blood pressure is higher in obese individuals than in nonobese individuals. However, the effect of lifestyle modification on central systolic blood pressure in obese individuals is unclear. The aim of this study was to determine whether lifestyle modification decreases central blood pressure in overweight and obese men. METHODS: Thirty-nine overweight and obese men (age, 49±2 years; BMI, 30±1 kg/m) were recruited into our study. We measured central systolic blood pressure and brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, before and after a 12-week lifestyle modification that included aerobic exercise and dietary modification. RESULTS: After the 12-week program, body mass, BMI, and waist circumstance decreased significantly. Central systolic blood pressure and baPWV were significantly decreased after the lifestyle modification in overweight and obese men. Furthermore, there was a significant correlation between the lifestyle modification-induced change in central systolic blood pressure and that in baPWV. CONCLUSION: This study showed for the first time that lifestyle modification-induced weight loss decreases central systolic blood pressure in overweight and obese men. The decrease in central systolic blood pressure was associated with the reduction in arterial stiffness. These results suggest that lifestyle modification-induced reduction in arterial stiffness may contribute toward the decreased central systolic blood pressure in overweight and obese men.

[Effects of self-selection of dietary sessions on weight loss, dropouts during the intervention, and weight maintenance after 1 year].

OBJECTIVES: To compare the effects of weekly or bi-weekly dietary sessions with the same number of total lecture hours, periods, and lecture contents on weight loss, dropouts during the intervention, and the weight loss maintenance after 1 year. METHODS: The study included 52 middle-aged women with at least 1 risk factor for cardiovascular disease (i.e., obesity, hypertension, dyslipidemia, and hyperglycemia) who were encouraged to lose weight. Thirty-seven women were assigned to the weekly class (self-selected weekly class group: n=26) or the bi-weekly class (self-selected bi-weekly class group: n=11) based on their preference. Fifteen women were assigned to the bi-weekly class against their will (bi-weekly class group). All groups participated in the same number of sessions (total, 26 h), and were instructed to reduce their dietary intakes to 1200 kcal/day for 13 weeks. The self-selected weekly class group attended a 2-h instructional session every week, whereas both the bi-weekly class groups received 1-h sessions twice a week. Data on the body weight of the participants was collected 1 year after the intervention using a self-administered questionnaire via mail. RESULTS: The self-selected bi-weekly class group had significantly fewer dropouts (self-selected weekly class group: 5 persons, 19.2%; self-selected bi-weekly class group: 1 person, 9.0%; bi-weekly class group: 8 persons, 53.3%; P<0.05). There was a significant decrease in weight (P<0.05) in all 3 groups during the intervention (self-selected weekly class group: -4.3±2.7 kg, self-selected bi-weekly class group: -6.7±3.0 kg, bi-weekly class group: -6.0±3.4 kg). However, weight loss in the self-selected bi-weekly class group was significantly greater than that in the other 2 groups. A significant change in body weight at the 1-year follow-up was not observed in any group (self-selected weekly class group: +0.4±1.3 kg, self-selected bi-weekly class group: -0.1±2.3 kg, bi-weekly class group: +0.5±0.6 kg). Repeated-measures ANOVA (time×group) revealed no significant interactions in weight loss. CONCLUSION: These results suggest that a greater frequency of dietary sessions contributes to weight loss, while a lesser frequency of dietary sessions contributed to a decrease in questionnaire recovery rates. The dropout rate in the self-selected weekly and bi-weekly class groups was lesser than that in the bi-weekly class group. Therefore, dietary sessions tailored to the needs of the participants might decrease the dropout rate.

Lifestyle modification decreases arterial stiffness and plasma asymmetric dimethylarginine level in overweight and obese men.

BACKGROUND: Increased arterial stiffness is an independent risk factor for cardiovascular disease. Arterial stiffness is higher in obese individuals than in nonobese individuals. Lifestyle modifications (i.e. exercise and dietary modification) decrease arterial stiffness in obese individuals. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, an enzyme responsible for the generation of nitric oxide. AIM: The aim of this study was to examine whether lifestyle modifications affect circulating levels of ADMA in overweight and obese men and, if they do, whether ADMA is involved in the mechanism underlying the decrease in arterial stiffness with lifestyle modification. METHODS: Seventeen overweight and obese men (BMI: 29.8±0.8 kg/m(2)) completed a 12-week lifestyle modification program, which included aerobic exercise and dietary modification. Before and after the intervention, we evaluated brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, and plasma ADMA concentration in all participants. RESULTS: After the 12-week lifestyle modification program, BMI and baPWV decreased significantly and the plasma ADMA concentration decreased markedly in overweight and obese men. There was a significant positive correlation between percent change in baPWV and plasma ADMA concentration. CONCLUSION: Lifestyle modifications reduce arterial stiffness and plasma ADMA concentration in overweight and obese individuals. A decrease in arterial stiffness was associated with a corresponding reduction in plasma ADMA concentrations. These results suggest that reductions in ADMA may be an important mechanism underlying the beneficial effect of lifestyle modification on arterial stiffness.

Association of plasma pentraxin 3 with arterial stiffness in overweight and obese individuals.

BACKGROUND: Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. The degree of arterial stiffness in obese individuals is greater than that in normal-weight subjects. Pentraxin 3 (PTX3) is mainly produced by vascular tissues and exerts a cardioprotective effect. However, the relationship between PTX3 and arterial stiffness in obese individuals has not yet been clarified. In this study, we examined the relationships between obesity, arterial stiffness, and PTX3 levels in 282 subjects. METHODS: All participants were classified as normal weight, overweight, or obese on the basis of their body mass index. We measured the brachial-ankle pulse wave velocity (baPWV; an index of arterial stiffness) and plasma PTX3 concentrations in all subjects. Additionally, the carotid-femoral PWV (cfPWV) was measured in 173 subjects. RESULTS: We found that baPWV and cfPWV in overweight and obese subjects were significantly higher than those in normal-weight subjects. Plasma PTX3 concentrations in normal-weight subjects were significantly higher than those in overweight and obese subjects. Moreover, PTX3 had a significant negative correlation with baPWV. However, stepwise multivariable linear regression analysis did not indicate any associations between these parameters. CONCLUSIONS: Arterial stiffness is increased in overweight and obese individuals. The increase in arterial stiffness may, at least in part, be associated with an obesity-related reduction in plasma PTX3 concentrations.

Generation of membrane diversity by lysophospholipid acyltransferases.

Glycerophospholipids are main components of cellular membranes and have numerous structural and functional roles to regulate cellular functions. Polyunsaturated fatty acids, such as arachidonic acid and eicosapentaenoic acid, are mainly located at the sn-2, but not the sn-1 position of glycerophospholipids in an asymmetrical manner and the fatty acid compositions at both the sn-1 and sn-2 positions differ in various cell types and tissues. Asymmetry and diversity of membrane glycerophospholipids are generated in the remodelling pathway (Lands' cycle), which are conducted by the concerted actions of phospholipases A2 (PLA2s) and lysophospholipid acyltransferases (LPLATs). The Lands' cycle was first reported in the 1950s. While PLA2s have been well characterized, little is known about the LPLATs. Recently, several laboratories, including ours, isolated LPLATs that function in the Lands' cycle from the 1-acylglycerol-3-phosphate O-acyltransferase family and the membrane bound O-acyltransferases family. In this review, we summarize recent studies on cloning and characterization of LPLATs that contribute to membrane asymmetry and diversity.