Genetic evidence for involvement of ß2-adrenergic receptor in brown adipose tissue thermogenesis in humans.

BACKGROUND: Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the ß-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding ß-ARs and BAT activity in human adults. METHODS: Single nucleotide polymorphisms (SNPs) in ß1-, ß2-, and ß3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIRTRS) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber. RESULTS: We found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIRTRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits. CONCLUSIONS: The present study supports the importance of ß2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor's BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function.

The impact of newspaper reporting of hydrogen sulfide suicide on imitative suicide attempts in Japan.

PURPOSE: An analysis model based on monthly or fortnight data is inadequate to precisely evaluate the impact of media reporting of suicide on suicide rates as well as the time lag from exposure to the report of a suicide. Thus, we used daily time-series data and examined the association between newspaper articles on suicide and suicide attempts in Japan. METHODS: The Box-Jenkins transfer function model was applied to daily time-series data for the period March 27-May 21, 2008. RESULTS: Newspaper articles on suicide using hydrogen sulfide at (t - 1) were related to suicide attempts at (t) (ps < 0.001 and 0.05). Newspaper articles on suicides using hydrogen sulfide on the front page at (t - 1) were related to suicide attempts at (t) (p < 0.00). The magnitude of the impact of newspaper articles about suicide at (t - 1) or (t - 3) on "copy-cat" suicide attempts became greater as the number of news articles violating the media suicide recommendations increased. CONCLUSIONS: The time lag between exposure to newspaper reports of suicide and attempts was 1 or 3 days, and the magnitude of the impact of front page articles was about four times as great as that of suicide articles in general.

Illusory self-motion (vection) may be inhibited by hypobaric hypoxia.

INTRODUCTION: Previous reports have shown that higher altitudes can alter human perception. We add further evidence to this claim, describing a new finding in which higher altitudes inhibit the perception of illusory self-motion, i.e., vection. METHOD: We compared vection strength under both normal and high altitude (hypobaric hypoxia) conditions. In the high altitude condition, atmospheric pressure in the climatic chamber was decreased to 13,123 ft (4000 m; 492 ft/150 m x min(-1)) for 28 min and then maintained at the 13,123-ft (4000-m) level for 30 min by a preprogrammed operation. Vection was induced by an optic flow stimulus. RESULTS: Significant differences were observed between the normal and high altitude conditions for all three of the vection strength measurements (latency, duration, and magnitude). Vection was decreased by 14.6%, and Spo2 was decreased by 16.7% in the hypoxia condition. CONCLUSION: Vection was inhibited in the high altitude condition. Applications of this finding include informing aircraft pilots of this effect of self-motion perception inhibition at higher altitudes to promote safer flying.

Endocrine, inflammatory and immune responses and individual differences in acute hypobaric hypoxia in lowlanders.

When lowlanders are exposed to environments inducing hypobaric hypoxia (HH) such as high mountains, hemodynamic changes occur to maintain oxygen levels in the body. However, changes to other physiological functions under such conditions have yet to be clarified. This study investigated changes in endocrine, inflammatory and immune parameters and individual differences during acute HH exposure using a climatic chamber (75 min of exposure to conditions mimicking 3500 m) in healthy lowlanders. Aldosterone and cortisol were significantly decreased and interleukin (IL)-6, IL-8 and white blood cell (WBC) counts were significantly increased after HH. Lower peripheral oxygen saturation (SpO2) was associated with higher IL-6 and WBC counts, and higher IL-8 was associated with higher cortisol. These findings suggest that endocrine, inflammatory and immune responses are evoked even with a short 75-min exposure to HH and individuals with lower SpO2 seemed to show more pronounced responses. Our results provide basic data for understanding the physiological responses and interactions of homeostatic systems during acute HH.

Association of EGLN1 genetic polymorphisms with SpO2 responses to acute hypobaric hypoxia in a Japanese cohort.

BACKGROUND: Recent studies have explored various genetic and physiological factors related to high-altitude adaptation in highlander populations. However, the effects of single nucleotide polymorphisms (SNPs), influencing such adaptation, on physiological responses to hypobaric hypoxia have not been examined in lowlanders with lowlander ancestry. Thus, we aimed to investigate the association between SNPs around the EGLN1 genomic region, possibly involved in high-altitude adaptation, and physiological changes to hypobaric hypoxia exposure in a cohort of Japanese lowlanders. METHODS: Physiological data were obtained from 46 healthy Japanese male students under different atmospheric pressure conditions (equivalent to sea level and altitudes of 2500 and 4000 m). Genotypes of seven SNPs around EGLN1 were determined in all subjects by PCR-direct sequencing or TaqMan SNP genotyping assay. RESULTS: Results of the association study suggest that percutaneous arterial oxygen saturation (SpO2) responses of individuals with rs12097901 and rs2790859 alleles, whose frequencies are high in highlander populations (HL alleles), may be susceptible to acute hypobaric hypoxia. SpO2 levels of individuals with HL alleles were lower than those of individuals with non-HL alleles. At the same time, the subjects with HL alleles did not appear to have any remarkable hematological or pulmonary features that may counteract the low levels of SpO2. One may hypothesize that the low SpO2 levels in HL allele carriers could be a risk factor for acute mountain sickness in Japanese population. CONCLUSIONS: Our findings suggest that rs12097901 and rs2790859 genotypes affect SpO2 responses and may be associated with the susceptibility to acute hypobaric hypoxia in Japanese population.

Experimental evidence reveals the UCP1 genotype changes the oxygen consumption attributed to non-shivering thermogenesis in humans.

Humans have spread out all over the world adapting to many different cold environments. Recent worldwide genome analyses and animal experiments have reported dozens of genes associated with cold adaptation. The uncoupling protein 1 (UCP1) gene enhances thermogenesis reaction in a physiological process by blocking ATP (adenosine triphosphate) synthesis on a mitochondrial membrane in brown adipose tissues. To our knowledge, no previous studies have shown an association between variants of the UCP1 gene and physiological phenotypes concerning non-shivering thermogenesis (NST) under the condition of low temperature in humans. We showed that the degree of NST for healthy subjects in an artificial climate chamber is significantly different among UCP1 genotypes. Defining the haplotypes covering the UCP1 region (39.4 kb), we found that the frequency of the haplotype with the highest NST was significantly correlated with latitudes and ambient temperature. Thus, the data in this study provide the first evidence that the UCP1 genotype alters the efficiency of NST in humans, and likely supports the hypothesis that the UCP1 gene has been related to cold adaptation in human evolutionary history.

Relationship between mitochondrial haplogroup and physiological responses to hypobaric hypoxia.

We aimed to investigate the relationship between mtDNA polymorphism and physiological responses to hypobaric hypoxia. The study included 28 healthy male students, consisting of 18 students in haplogroup D and 10 in haplogroup M7+G. Measurement sensors were attached to the participants for approximately 30 min in an environment with a temperature of 28 °C. After resting for 15 min, the programmed operation of the hypobaric chamber decreased the atmospheric pressure by 11.9 Torr every minute to simulate an increase in altitude of 150 m until 9.7 Torr (equivalent to 2500 m) and then decreased 9.7 Torr every minute until 465 Torr (equivalent to 4000 m). At each altitude, the pressure was maintained for 15 min and various measurements were taken. Haplogroup D showed higher SpO2 (p < 0.05) and significantly higher SpO2 during the pressure recovery period when compared with haplogroup M7+G. The distal skin temperature was higher in haplogroup D when compared with M7+G. These results suggested that haplogroup D maintained SpO2 at a higher level with higher peripheral blood flow during acute hypobaric exposure.

Seasonal variation of non-shivering thermogenesis (NST) during mild cold exposure.

BACKGROUND: The physiological function of non-shivering thermogenesis (NST) has been investigated in recent years, and some studies have discussed the importance of NST with respect to human cold adaptation. The present study aimed to clarify individual and seasonal variations in NST that occurred as a result of mild cold exposure. METHODS: Seventeen male university students participated in the present study during summer and winter. The climate chamber used was programmed so that ambient temperature dropped from 28°C to 16°C over an 80-min period. Physiological parameters of test subjects were recorded during the experiments. RESULTS: Increases in oxygen intake (VO2) during cold exposure were significantly greater without shivering in winter than they were in summer. Respiratory exchange ratio (RER) was significantly lower during thermoneutral baseline and cold exposure in winter than it was during the same periods in summer. In addition, there was a significant negative correlation between ΔVO2 and ΔRER. CONCLUSIONS: Increase of VO2 without shivering indicated increase of NST, and decrease of RER depends on the metabolization of fat in winter. These results suggested that NST activity was activated by seasonal acclimatization, and individual variation of NST depends on individual variation of fat metabolism.

Gender difference in N170 elicited under oddball task.

BACKGROUND: Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. FINDINGS: Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in response to the target. Clear N170 was elicited in response to target and non-target stimuli in both males and females. However, females showed more negative amplitude of N170 in response to target compared with non-target, while males did not show different N170 responses between target and non-target. CONCLUSIONS: The present results suggest that females have a characteristic of allocating attention at an early stage when responding to faces actively (target) compared to viewing faces passively (non-target). This supports previous findings suggesting that task demand is an important factor in gender differences in N170.

Time window for cognitive activity involved in emotional processing.

BACKGROUND: From previous studies it is becoming evident that the processing of unpleasant stimuli occurs early (0 to 300 ms); however, it is not clear how cognitive processing related to pleasant/unpleasant emotions occurs at later time windows (≥ 300 ms). On the other hand, as evident from the previous reports, BIS and BAS personality traits are strongly associated with unpleasant and pleasant responses, respectively. Therefore, in the present study, we aim to identify the time window involved in human pleasant/unpleasant emotional processing by investigating ERP components correlated with BIS/BAS personality traits. METHODS: Twenty-nine men took part in the study and recording ERP during presented sounds. BIS/BAS score was calculated using the Japanese edition of the BIS/BAS questionnaire. RESULTS: Significant correlation was not observed between BIS and BAS scores. A significant and positive correlation was observed between N100 amplitude and BIS score. A positive correlation was found between BAS fun seeking subscale score and LPP amplitude. Our findings did not contradict previous study results. CONCLUSIONS: Our results suggest that the processing of unpleasant emotions takes place early on, since N100 response was larger in high BIS subjects who are known to be sensitive to unpleasant emotions. LPP was larger in high BAS subjects who are known to be sensitive to pleasant emotions. The LPP was considered to be augmented because the ACC activity level during pleasant emotions reflected on LPP.

Effect of empathy trait on attention to various facial expressions: evidence from N170 and late positive potential (LPP).

BACKGROUND: The present study sought to clarify the relationship between empathy trait and attention responses to happy, angry, surprised, afraid, and sad facial expressions. As indices of attention, we recorded event-related potentials (ERP) and focused on N170 and late positive potential (LPP) components. METHODS: Twenty-two participants (12 males, 10 females) discriminated facial expressions (happy, angry, surprised, afraid, and sad) from emotionally neutral faces under an oddball paradigm. The empathy trait of participants was measured using the Interpersonal Reactivity Index (IRI, J Pers Soc Psychol 44:113-126, 1983). RESULTS: Participants with higher IRI scores showed: 1) more negative amplitude of N170 (140 to 200 ms) in the right posterior temporal area elicited by happy, angry, surprised, and afraid faces; 2) more positive amplitude of early LPP (300 to 600 ms) in the parietal area elicited in response to angry and afraid faces; and 3) more positive amplitude of late LPP (600 to 800 ms) in the frontal area elicited in response to happy, angry, surprised, afraid, and sad faces, compared to participants with lower IRI scores. CONCLUSIONS: These results suggest that individuals with high empathy pay attention to various facial expressions more than those with low empathy, from very-early stage (reflected in N170) to late-stage (reflected in LPP) processing of faces.

The aging population and future demand for emergency ambulances in Japan.

Demand for emergency ambulances has been increasing in developmentally advanced countries, and in Japan demand has been increasing due to the aging population since 2008, when the total population began to decrease. However, we do not know how acceleration of the aging population relates to the demand for emergency ambulances. Thus, we estimated future demand for emergency ambulances in Japan. A regression with autocorrelated errors model was used to estimate future demand for emergency ambulance dispatches and emergency transports. In the estimation, data on emergency ambulance dispatches, emergency transports, and population data from 1963 to 2011, and an estimate of the population of Japan from 2012 to 2025 were used. The number of emergency ambulance dispatches has increased since 2008, and it is expected to continue to increase until around 2023 or 2024, when it will reach a peak of ~6.2 million per year. Similarly, the number of emergency transports is expected to continue to increase until 2022 or 2023, when it will reach a peak of ~5.3 million per year. Although we need to be careful when evaluating numbers predicted for the remote future due to methodological limitations, the findings might be useful for updating emergency medical care systems to prepare for future increases in demand.

Relationship between seasonal cold acclimatization and mtDNA haplogroup in Japanese.

BACKGROUND: The purpose of this study was to elucidate the interaction between mtDNA haplogroup and seasonal variation that contributes to cold adaptation. METHODS: There were 15 subjects (seven haplotype D subjects and eight haplotype non-D subjects). In summer and winter, the subjects were placed in an environment where the ambient temperature dropped from 27 °C to 10 °C in 30 minutes. After that, they were exposed to cold for 60 minutes. RESULTS: In summer, the decrease in rectal temperature and increase in oxygen consumption was smaller and cold tolerance was higher in the haplotype non-D group than in the haplotype D group. In winter, no significant differences were seen in rectal temperature or oxygen consumption, but the respiratory exchange ratio decreased in the haplotype D group. CONCLUSIONS: The results of the present study suggest that haplogroup D subjects are a group that changes energy metabolism more, and there appears to be a relationship between differences in cold adaptability and mtDNA polymorphism within the population. Moreover, group differences in cold adaptability seen in summer may decrease in winter due to supplementation by seasonal cold acclimatization.