Link between MnSOD Ala16Val (rs4880) polymorphism and asthma risk is insignificant from sequential meta-analysis

The mitochondrial manganese superoxide dismutase (MnSOD) enzyme protects lungs against oxidative stress by neutralizing the free radical superoxide produced in the respiratory function. This has relevance to asthma. Therefore, it is of interest to describe the potential effect of MnSOD Ala16Val genetic polymorphism to asthma risk. Known data in this context is inconclusive in nature. The possible link between MnSOD Ala16Val polymorphism and asthma is explored using sequence meta-analysis. Data from the pooled analysis of MnSOD Ala16Val polymorphism using five genetic models i.e., allelic (Val vs. Ala: p=0.846; OR=1.033, 95% CI=0.742 to 1.440) is discussed. Homozygous (Val Val vs. Ala Ala: p=0.517; OR=1.307, 95% CI=0.582 to 2.932) and heterozygous (Val Ala vs. Ala Ala: p=0.307; OR=1.138, 95% CI=0.888 to 1.459) data using the described models are documented. Data from the dominant model (Val Val + Val Ala vs. Ala Ala: p=0.301; OR=1.289, 95% CI=0.797 to 2.085) and the recessive model (Val Val vs. Val Ala + Ala Ala: p=0.761; OR=0.924, 95% CI=0.555 to 1.538) analyses for several ethnic subgroups in this context is reported.     

Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early-onset prostate cancer

Prostate cancer continues to be the most frequently diagnosed neoplasm, and the second leading cause of cancer-related mortality in men. Oxidative stress may enhance prostatic carcinogenesis. Manganese superoxide dismutase (MnSOD) is the only known superoxide scavenger in mitochondria. It plays a key role in antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T-->C single nucleotide substitution, resulting in a Val-->Ala change at position 9 (Ala-9Val), which alters the secondary structure of the protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85 prostate cancer cases and 151 control subjects. Ala-9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in prostate cancer susceptibility in the subjects with Ala/Ala and Val/Ala genotype compared with Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69-2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non-aggressive prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2-fold increased risk of early-onset prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of prostate cancer, but no impact on the subsequent development of the disease.     

Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility

Within mitochondria, manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species (ROS). An alanine-9valine (Ala-9Val) polymorphism in the mitochondrial targeting sequence of MnSOD has been described and has recently been associated with risk of human breast cancer. Our present case-control study was performed to explore the association between MnSOD genetic polymorphism and individual susceptibility to breast cancer. Ala-9Val polymorphism in the signal sequence of the protein for MnSOD was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a study population. There was no significant difference in risk for breast cancer development between patients positive and negative for the MnSOD Ala allele with adjusted odds ratio (OR): 0.86 (95% confidence interval (CI(0.43 to 1.72). When MnSOD Ala was combined with either cytochrome P450 1B1 CYP1B1*1 and catechol O-methyltransferase COMT-L (V158M) genotypes, the risk for developing breast cancer was significantly increased in patients with a body mass index (BMI) greater than 24 kg m(-2) (OR: 1.42 (95%CI=1.04-1.93)).     

Genetic polymorphism in the manganese superoxide dismutase gene is associated with an increased risk for hepatocellular carcinoma in HCV-infected Moroccan patients

Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The main risk factors for its development are hepatitis B and C virus infections. Hepatitis B and C viruses induce chronic inflammation and oxidative stress that could predispose a cell to mutagenesis and proliferation. Manganese superoxide dismutase (MnSOD) catalyses the detoxification of free radicals, thus playing a crucial role in the protection against damage. A valine (Val) to alanine (Ala) substitution at amino acid 9, mapping within the mitochondrion-targeting sequence of the MnSOD gene, has been associated with an increased cancer risk. The aim of our study was to investigate a possible association of the Val/Ala-MnSOD polymorphism and HCC development in Moroccan patients. Genotypes were determined by means of PCR and RFLP analysis in 96 patients with HCC and 222 control subjects matched for age, sex, and ethnicity. Homozygous Ala/Ala carriers were 31% in the cases and 18% in the controls, which corresponds to an odds ratio (OR) of 2.89, with a 95% confidence interval (CI) of 1.47-5.68. Stratification into subgroups based on HCV infection status revealed an even more increased risk for homozygous Ala/Ala carriers with hepatitis C infection (38.2% in the cases versus 14.8% in the control subjects OR, 5.09; 95% CI, 1.76-14.66). Our findings provide further evidence of an association between the Ala-9Val MnSOD polymorphism and HCC occurrence in hepatitis C virus-infected Moroccan patients.     

Association of obesity and circulating adipose stromal cells among breast cancer survivors

A positive association of obesity with breast cancer incidence and mortality is well established. Recent reports indicate that adipose stromal cells (ASCs) play an important role in breast cancer development and progression by producing estrogens and tumor-promoting cytokines. Furthermore, circulating ASCs have been uniquely detected in obese individuals, which is likely due to increased tissue remodeling and cell mobilization. The number of circulating ASCs is even more prominent in obese patients with colon and prostate cancers, both of which are exacerbated by obesity. To determine whether a similar association exists for breast cancer, we collected blood samples from a cohort of breast cancer survivors and enumerated circulating ASCs by flow cytometry on the basis of the previously established ASC-associated immunophenotype (CD34⁺/CD31^?/CD45^?). We found significantly higher levels of circulating ASCs (p < 0.001) in breast cancer survivors with body mass index (BMI) ≥30 kg/m² than their non-obese counterparts (BMI < 30). We also compared circulating ASCs before and after exercise of only the obese subjects enrolled in a 6-month individualized exercise program, but found no statistically significant difference, likely due to limited number of subjects in the study. Our findings suggest that circulating ASCs can serve as a potential biomarker for future studies of the impacts of obesity and physical activity on breast cancer recurrence and survival.     

Increased prevalence of MnSOD genetic polymorphism in endurance and power athletes

Abstract

The purpose of the current study was to determine the frequency distribution of manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism (rs1799725) among 195 trained endurance and power athletes and 240 healthy controls. Genomic DNA was extracted using a standard protocol. Genotyping of the MnSOD Val-9Ala polymorphism was performed using polymerase chain reaction (PCR). Results showed a higher proportion of the Val/Ala and Ala/Ala genotype, and a lower proportion of Val/Val genotype, in the athletes group compared with that of the controls. The Ala allele frequency was significantly higher (p < 0.001) in the athletes group (46%) compared with that in the control (29%). Interestingly, there was no difference between the endurance and power athletes. In addition, the frequency of Ala/Ala genotype was significantly higher (p < 0.05) among top (international and Olympic-level) athletes (29%) compared with that among national-level endurance and power athletes (17%). We conclude that 1) the Ala allele is more frequent in athletes than in controls; and 2) the higher frequency of the Ala allele was noted in both endurance and power athletes compared with that in controls, suggesting that the positive association between the Ala allele and athletic performance may be related to ROS-related angiogenesis, mitochondrial biosynthesis, and muscle hypertrophy, and not to MnSOD aerobic properties.     

Polymorphism in the manganese superoxide dismutase gene

Oxidative stress and mitochondrial damage occur in sepsis. Manganese superoxide dismutase (MnSOD) provides the main defence against oxidative stress within mitochondria. Ala9Val is a single nucleotide polymorphism (SNP) in the MnSOD gene, predicted to affect intra-mitochondrial transport of the enzyme. We found a significant difference in the genotype frequency between healthy subjects (n = 100) and patients with sepsis (n = 40, p = 0.009). For assessment of functionality ten healthy subjects of each homozygous genotype (A/A or V/V) were studied. Peripheral blood mononuclear cells were separated and incubated for 18 h with lipopolysaccharide (LPS), followed by analysis of mitochondrial and cytosolic fractions. There was no difference between genotypes in MnSOD activity and cytochrome c concentration, and minor differences in total antioxidant capacity (TAC) and mitochondrial membrane potential, which did not affect response to LPS. Despite predictions from structural enzyme studies that mitochondrial trafficking would be affected by the Ala9Val polymorphism of the MnSOD gene had little functional effect.     

Increased risk of advanced prostate cancer associated with MnSOD Ala-9-Val gene polymorphism

We aimed to investigate the association between manganese superoxide dismutase (MnSOD) Ala-9-Val gene polymorphism and the initiation and/or progression of prostate cancer (PCa) as well as to evaluate its potential interactions with advanced age and smoking status. MnSOD Ala-9-Val gene polymorphism was carried out in 134 (mean age 64.1 ± 7.48) PCa patients and 159 (mean age 62.5 ± 7.53) healthy controls with serum prostate specific antigen (PSA) levels (<4 ng/ml) and normal digital rectal examination (DRE) findings in this prospectively designed study. PCa patients were classified as low stage disease (T₁ or T₂ and N₀M₀ stages) and high stage disease (T₃ or T₄ and N₀M₀ or N₁ or M₁ stages). Genotypes for MnSOD Ala-9-Val gene polymorphism were identified by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL). Despite lack of association between different genotypes of MnSOD Ala-9-Val gene polymorphism and the presence of PCa, patients with Ala/Ala genotype were at an increased risk of high stage disease compared with those with the Val/Val genotype [odds ratio (OR), 3.77; 95% CI, 1.30–10.94; P = 0.012]. However, no significant difference was observed in the distribution of each genotype among PCa patients, with respect to tumor grade. On the other hand, smoking status and aging did not seem to change the association between genotypes and PCa risk. Ala/Ala genotype of MnSOD polymorphism may have an effect on adverse features of PCa such as high stage disease.     

Association among oxidized LDL levels, MnSOD, apolipoprotein E polymorphisms, and cardiovascular risk factors in a south Brazilian region population

Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.     

Association of the UCP polymorphisms with susceptibility to obesity: case–control study and meta-analysis

This paper describes a case–control study and a meta-analysis performed to evaluate if the following polymorphisms are associated with presence of obesity: ?3826A/G (UCP1); ?866G/A, Ala55Val and Ins/Del (UCP2) and ?55C/T (UCP3). The case–control study enrolled 282 obese and 483 non-obese patients with type 2 diabetes. A literature search was made to identify all studies that evaluated associations between UCP1–3 polymorphisms and obesity. In the case–control study the distributions of the UCP variants did not differ between obese and non-obese groups (P > 0.05). Forty-seven studies were eligible for the meta-analysis and the results showed that the UCP2 ?866G/A and UCP3 ?55C/T polymorphisms were associated with protection to obesity in Europeans (OR = 0.89, 95 % CI 0.82–0.97 and OR = 0.88, 95 % CI 0.80–0.97, respectively). The UCP2 Ala55 val polymorphism was associated with obesity in Asians (OR = 1.61, 95 % CI 1.13–2.30). The UCP2 Ins/Del polymorphism was associated with obesity mainly in Europeans (OR = 1.19, 95 % CI 1.00–1.42). There was no significant association of the UCP1 ?3826A/G polymorphism with obesity. In our case–control study we were not able to demonstrate any association between UCP polymorphisms and obesity in T2DM patients; however, in the meta-analysis we detected a significant association of UCP2 ?866G/A, Ins/Del, Ala55Val and UCP3 ?55C/T polymorphisms with obesity.     

Polymorphism in the manganese superoxide dismutase gene

Oxidative stress and mitochondrial damage occur in sepsis. Manganese superoxide dismutase (MnSOD) provides the main defence against oxidative stress within mitochondria. Ala9Val is a single nucleotide polymorphism (SNP) in the MnSOD gene, predicted to affect intra-mitochondrial transport of the enzyme. We found a significant difference in the genotype frequency between healthy subjects (n = 100) and patients with sepsis (n = 40, p = 0.009). For assessment of functionality ten healthy subjects of each homozygous genotype (A/A or V/V) were studied. Peripheral blood mononuclear cells were separated and incubated for 18 h with lipopolysaccharide (LPS), followed by analysis of mitochondrial and cytosolic fractions. There was no difference between genotypes in MnSOD activity and cytochrome c concentration, and minor differences in total antioxidant capacity (TAC) and mitochondrial membrane potential, which did not affect response to LPS. Despite predictions from structural enzyme studies that mitochondrial trafficking would be affected by the Ala9Val polymorphism of the MnSOD gene had little functional effect.     

Ethnic variation in the mitochondrial targeting sequence polymorphism of MnSOD.

In contrast to CuZn superoxide dismutase (SOD), only a very limited number of mutations have been described in MnSOD. One interesting example is a polymorphism (Ala-9Val) in the mitochondrial targeting sequence of this radical-scavenging enzyme. We have studied the Ala-9Val polymorphism in various ethnic groups by means of the oligonucleotide ligation assay. There were significant variations in this unique polymorphism between three different language groups: Baltic (Lithuanians), Finnic (Finns and Saamis) and Germanic (Swedes). The Ala frequency in an Asiatic population (Chinese) was significantly lower than in most European populations. This polymorphism may affect the mitochondrial targeting rate of MnSOD which may result in mitochondrial damage with implication in various late-onset neurological diseases.     

Association between Gene Polymorphism of Manganese Superoxide Dismutase and Prostate Cancer Risk

Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and protects cells from reactive oxygen species‐induced oxidative damage. The aim of this study was to investigate the association between MnSOD Ala‐9Val gene polymorphism and prostate cancer (PCa) risk in Turkish men with prostate cancer. 33 patients with PCa and 81 control individuals were included in the study. We observed an association between MnSOD Ala/Ala frequency and a higher PCa risk. In addition, we found that the increased risk of early‐onset PCa (under age of 65) in the men homozygous for Ala allele was higher than the men homozygous for Val allele. However, we determined that MnSOD Ala‐9Val genotype was not associated with the aggressiveness of the disease. The results of our study suggest that MnSOD Ala/Ala genotype may influence on early‐onset of PCa patients, but no effect on subsequent development of the disease in Turkish men. However, our study has a limitation that is small numbers of individuals for cases and controls. Therefore, the presented study limited our statistical power to fully investigate the gene polymorphism on cancer risk. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:213‐218, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21472     

Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells

Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O(2)(-)). The superoxide dismutase manganese dependent (SOD2) catalyzes O(2)(-) in H(2)O(2) into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-α, IFN-γ). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question.     

Effect of ID ACE gene polymorphism on dietary composition and obesity-related anthropometric parameters in the Czech adult population

The aim of this study was to investigate the possible associations between insertion/deletion (ID) polymorphism in angiotensin-converting enzyme (ACE) (dbSNP rs 4646994) with the food intake and body composition in the Czech non-obese, obese and extremely obese populations. A total of 453 various-weighted individuals were enrolled in the study and were according to their BMI assigned into following subgroups, such as obese (30 ≤ BMI < 40), morbidly obese (BMI ≥40) and non-obese (20 < BMI < 30) subjects. Both the obese cases and the non-obese controls underwent the identical subset of standardized examinations (BMI, % body fat, waist-to-hip ratio, skin fold thickness, native dietary composition examined by 7-day food records, etc.). No significant case–control differences in genotype distributions or allelic frequencies were observed. There were no differences in genotype frequencies between males and females either. The prevalence of obesity was significantly higher among subjects with the II genotype (42 %) when compared with those with DD (36%) and those with ID (37%) genotypes (P = 0.04). When compared with carbohydrate intake in the whole studied cohort, the odds ratios of carrying the DD allele in the morbidly obese cohort were 0.84 (95% CI 0.34, 2.10, P = 0.17), 0.27 (0.07, 0.98, P = 0.02), and 4.25 (1.44, 12.51, P = 0.005) in those individuals consuming <210, 210–260, and >260 g of carbohydrates/day, respectively. Based on our findings, the ID ACE polymorphism could represent a gene modulator of carbohydrate intake in morbidly obese Czech population; the strong significant effect of DD genotype was observed in the phenotypes of extreme obesity with the highest carbohydrate intake.     

Normal weight diabetic patients versus obese diabetics: relation of overall and abdominal adiposity to vascular health

Background

Obesity is associated with increased risk for stroke. The breath-holding index (BHI) is a measure of vasomotor reactivity of the brain which can be measured with the transcranial Doppler (TCD). We aim to evaluate obesity as an independent factor for altered cerebrovascular reactivity.

Methods

Cerebrovascular hemodynamics (mean flow velocities MFV, pulsatility index, PI, resistance index, RI, and BHI) was determined in 85 non-obese (Body Mass Index, BMI ≤27 kg/m²) and 85 obese subjects (BMI ≥35 kg/m²) without diabetes mellitus and hypertension. Anthropometric and metabolic variables, and scores to detect risk for obstructive sleep apnea (OSA) were analyzed for their association with the cerebrovascular reactivity.

Results

The BHI was significantly lower in subjects with obesity according to BMI and in subjects with abdominal obesity, but the PI and RI were not different between groups. There was a linear association between the BMI, the HOMA-IR, the Matsuda index, the waist circumference, and the neck circumference, with the cerebrovascular reactivity. After adjusting for insulin resistance, neck circumference, and abdominal circumference, obesity according to BMI was negatively correlated with the cerebrovascular reactivity.

Conclusions

We found a diminished vasomotor reactivity in individuals with obesity which was not explained by the presence of insulin resistance.     

Prevalence of Uncomplicated Obesity in an Italian Obese Population

Objective: The existence of healthy obese subjects has been suggested but not clearly reported. We sought to address the prevalence of uncomplicated obesity and adverse risk factors in a large Italian obese population. Research Methods and Procedures: This was a cross‐sectional study of a population of consecutive Italian obese subjects. We studied 681 obese subjects (514 women and 167 men), with a mean age of 41.1 ± 13.9 years (range, 16 to 77 years), mean BMI of 40.2 ± 7.6 kg/m² (range, 30 to 89.8 kg/m²), and a history of obesity for 20.5 ± 7 years (range, 10.5 to 30 years). Anthropometric, metabolic, cardiac, and obesity‐related risk factors were evaluated. Results: The prevalence of uncomplicated subjects was 27.5%, independent of BMI and duration of obesity. The youngest group of obese subjects showed a higher, but not statistically significantly higher, prevalence of uncomplicated obesity. No statistical difference for the prevalence of impaired fasting glucose, glucose intolerance, high triglycerides, high total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol among BMI categories (from mild to extremely severe obesity degree) was found. Obese subjects with BMI >50 kg/m² showed a higher prevalence of high blood pressure only when they were compared with the group with a BMI of 30 to 35 kg/m² (p < 0.01). Obese subjects with BMI >40 kg/m² showed a higher prevalence of hyperinsulinemia than subjects with BMI 30 to 35 kg/m² (p < 0.01). Discussion: This study shows that a substantial part of an Italian obese population has uncomplicated obesity, and the prevalence of adverse risk factors in this sample is unexpectedly low and partially independent of obesity degree. Uncomplicated obesity could represent a well‐defined clinical entity.     

The Pro12Ala Polymorphism of the PPARγ2 Gene Regulates Weight from Birth to Adulthood

Objective: The Pro12Ala polymorphism in exon B of peroxisome proliferator‐activated receptor γ 2 (PPARγ2) gene has been related to obesity, insulin resistance, and risk of type 2 diabetes. In this study, the effect of the Pro12Ala polymorphism on long‐term changes in weight and body composition was investigated. Research Methods and Procedures: The Pro12Ala polymorphism was genotyped in 311 subjects who participated in our previous population‐based study. In that study, weight at birth, 7 years, 20 years, and 41 years, and ponderal index at birth and BMI and waist circumference at 41 years were recorded. Results: The Ala12 allele of the PPARγ2 gene was associated with high ponderal index at birth (2.77 ± 0.27 kg/m³ in subjects with the Ala12Ala genotype, 2.79 ± 0.29 kg/m³ in subjects with the Pro12Ala genotype, and 2.63 ± 0.25 kg/m³ in subjects with the Pro12Pro genotype, p = 0.007, adjusted for gender) and weight at 7 years (p = 0.045) and tended to be associated with high birth weight (p = 0.094). Subjects with this allele gained less weight between 7 and 20 years (p = 0.043) and more weight between 20 and 41 years (p = 0.001) and ended up having higher waist circumference (p = 0.040) in adulthood than did subjects with the Pro12Pro genotype. Discussion: We conclude that the Pro12Ala polymorphism of the PPARγ2 gene regulates weight and body composition from utero to adulthood.     

Attenuated thermoregulatory responses with increased plasma osmolality in obese subjects during two seasons

Obese subjects may be more vulnerable to injury from heat stress, and appear to be less efficient at thermoregulation. Sweat rate, tympanic temperature and osmolality in obese subjects were investigated in Japan during two seasons. The purpose of this study was to examine the relationship between obesity, thermoregulatory response and season. Five obese (BMI, 32.0?±?4.9 kg/m²) and five non-obese (BMI, 23.2?±?2.9 kg/m²) men participated in this experiment at latitude 35°10′ N and longitude 136°57.9′E. The average atmospheric temperature was 29.1?±?1.0 °C in summer and 3.3?±?1.4 °C in winter. Tympanic temperature and sweat rate were measured during leg water immersion at 42 °C for 30 min. Blood samples were analyzed for plasma osmolality. The relationship between tympanic temperature and sweat rate decreased significantly in obese compared to in non-obese subjects in both seasons, there being a lowered sweat rate for any core temperature in obese subjects. Plasma osmolality was significantly higher in obese than in non-obese subjects in both seasons. Thermal sensation increased significantly in non-obese than in obese in winter but not in summer. Our data show that thermoregulatory responses are attenuated in obese subjects compared with controls, suggesting that obese people are at increased risk of heat-related illnesses.     

Seasonal differences in melatonin concentrations and heart rates during sleep in obese subjects in Japan

During the past several decades, obesity has been increasing globally. In Japan, obesity is defined by a BMI of 25 kg/m² or over; 28.6 % of men and 20.6 % of women are obese. Obese people have an increased incidence of developing cardiovascular, renal, and hormonal diseases and sleep disorders. Obese people also have shortened sleep durations. We investigated seasonal differences in melatonin concentrations, heart rates, and heart rate variability during sleep in obese subjects in Japan. Five obese (BMI, 32.0?±?4.9 kg/m²) and five non-obese (BMI, 23.2?±?2.9 kg/m²) men participated in this study in the summer and winter. Electrocardiograms were measured continuously overnight in a climatic chamber at 26 °C with a relative humidity of 50 %. Saliva samples for melatonin were collected at 2300 hours, 0200 hours, and 0600 hours. We found that melatonin concentrations during sleep in obese subjects were significantly lower than those in non-obese subjects in the winter. Heart rate during sleep in winter was significantly higher than that in summer in both obese and non-obese subjects. Heart rate variability was not significantly different in the summer and winter in both obese and non-obese subjects. Our results show that decreased nocturnal melatonin concentrations during winter in obese men may be related to higher heart rates, and this may suggest that obese men are at an increased risk of a cardiovascular incident during sleep, especially in the winter.