Narumi Nagai

Genetic polymorphisms of the renin-angiotensin system and obesity-related metabolic changes in response to low-energy diets in obese women

OBJECTIVE Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss. METHODS Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system. RESULTS Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P < 0.05). The AT₂R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P < 0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P < 0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P < 0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P < 0.05) than the C/C plus C/A genotypes. CONCLUSION The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT₂R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.

The −3826 A → G variant of the uncoupling protein-1 gene diminishes thermogenesis during acute cold exposure in healthy children

SUMMARY Uncoupling protein-1 (UCP1) activity in brown adipose tissue increases energy expenditure, and contributes to diet-induced or cold-induced thermogenesis. We previously reported that children with -3826 A → G nucleotide variant of the UCP1 gene had lowered postprandial thermogenesis in response to a high-fat meal. In this study, we investigated whether the UCP1 polymorphism was associated with cold-induced thermogenesis in healthy children. Resting energy expenditure was measured in 19 children (6-10 years) by indirect calorimetry for 30 min under thermoneutral (25 °C) or cold conditions (10 °C) in an environmental chamber. The activity of autonomic nervous system (ANS) was assessed by power spectral analysis of heart rate variability (HRV). Samples of saliva were collected for cortisol determination at the end of the experimental session. Each experiment was performed on 2 consecutive days. Children were genotyped for the UCP1 polymorphism with a PCR-restriction fragment length analysis using buccal samples. During cold exposure, total power of the HRV, an index of the overall ANS activity, as well as the salivary cortisol concentration significantly increased in the children with homozygous (GG) for the UCP1 polymorphism while only cortisol response was found in the carriers of the wild-type (AA) and heterozygous (AG) alleles; however, the GG allele group showed a lower cold-induced thermogenesis compared to the AA + AG group. In conclusion, despite cold-induced autonomic stimulation, the GG allele carriers have a reduced capacity for thermogenesis in response to acute cold exposure, suggesting that such reduced UCP1-linked thermogenesis may have adverse effects on the regulation of body weight.:

The CLOCK 3111T/C SNP is associated with morning gastric motility in healthy young women

Circadian locomotor output cycles kaput (CLOCK) molecule plays major roles in circadian rhythmicity and regulates daily physiological processes including digestive activity. Therefore, we hypothesized that the CLOCK 3111T/C single nucleotide polymorphism (SNP) might have adverse effects on the regulation of gastric motility. Based on the hypothesis, we investigated whether this SNP was associated with morning gastric motility. Ninety-five female university students (19.6±0.2 years) completed life-style questionnaires. Gastric motility, evaluated by electrogastrography (EGG), blood pressure (BP), and heart rate variability (HRV) were measured at 8:30 a.m. after an overnight fast. To determine the gastric motility, the spectral powers and dominant frequency (DF, a peak of the spectrum) of the EGG were calculated. No significant differences were found in breakfast frequency, energy intake, or HRV between CLOCK 3111T/C minor C allele (T/C or C/C) and T/T subjects. However, C allele carriers showed significantly lower DF than T/T subjects, suggesting slower gastric motility. Moreover, C allele carriers had a lower heart rate (HR) and tended to have lower diastolic BP compared with T/T subjects. These results support our hypothesis that this SNP is likely correlated with morning gastric motility. Such attenuated gastric and cardiovascular function that characterized CLOCK 3111C allele carriers could be affecting biological behavior in the morning.

The Association Between the Uncoupling Protein-1 Gene A-3826G Polymorphism and High-density Lipoprotein Cholesterol in A General Japanese Population: A Consideration of the Obesity Status

Background Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects. Methods Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m2, and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. Results The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group. Conclusions The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol. Keywords Obesity; Body mass index; HDL-C; Atherosclerotic risk

Circadian Rhythm Genes CLOCK and PER3 Polymorphisms and Morning Gastric Motility in Humans

Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER3 4/5 or PER3 5/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER3 4/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER3 4/5 or PER3 5/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER3 4/4 genotype, T/C or C/C and PER3 4/4 genotypes, and T/T and PER3 4/5 or PER3 5/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut.

Oral Carbonation Attenuates Feeling of Hunger and Gastric Myoelectrical Activity in Young Women

We previously reported that carbonated water ingestion induced fullness and gastric motility. In order to determine whether such satiating effects occur through oral carbonic stimulation alone, we conducted modified sham-feeding (SF) tests (carbonated water ingestion (CW), water ingestion (W), carbonated water sham-feeding (CW-SF), and water sham-feeding (W-SF)), employing an equivalent volume and standardized temperature of carbonated and plain water, in a randomized crossover design. Thirteen young women began fasting at 10 p.m. on the previous night and were loaded with each sample (15ºC, 250 mL) at 9 a.m. on separate days. Electrogastrography (EGG) recordings were obtained from 20 min before to 45 min after the loading to determine the power and frequency of the gastric myoelectrical activity. Appetite was assessed using visual analog scales. After ingestion, significantly increased fullness and decreased hunger ratings were observed in the CW group. After the load, transiently but significantly increased fullness as well as decreased hunger ratings were observed in the CW-SF group. The powers of normogastria (2-4 cpm) and tachygastria (4-9 cpm) showed significant increases in the CW and W groups, but not in the CW-SF and W-SF groups. The peak frequency of normogastria tended to shift toward a higher band in the CW group, whereas it shifted toward a lower band in the CW-SF group, indicating a different EGG rhythm. Our results suggest that CO2-induced oral stimulation is solely responsible for the feeling of satiety. Moreover, different gastric-contraction rhythms (slow or fast) were induced by oral carbonic stimulation alone and carbonated water ingestion.

Short-term Effects of Supplementation with a Multi-ingredient Weight-loss Product on Weight Maintenance and Fat Oxidation in Obese Female with Weight Reduction: Preliminary Results

Background: Numerous multi-ingredient weight-loss supplementation products are marketed, whereas the effects of these supplements on weight maintenance have rarely been studied. This study aimed to investigate preliminarily whether a 4-week supplementation of a multi-ingredient weight-loss product (named ‘diet’s BB’), containing L-carnitine, banaba, caffeine, capsaicin, Nelumbo nucifera leaf extract and sesamin, could contribute to weight maintenance and its related parameters among obese women with weight reduction following a Low-calorie Diet (LCD). Methods: In a prospective, randomized, double-blind intervention design, subjects with ≥5% of weight reduction following LCD were randomized to the group who used the diet’s BB (Group A) or tablet containing six types of vitamins (Group B) for four weeks. Their body weight and related parameters, including Respiratory Quotient (RQ) and fat oxidation, were measured pre- and post-intervention. Results: The changes in body weight and related parameters were not significantly different between the groups. Group A showed significantly reduced RQ and increased fat oxidation more than the Group B. Conclusion: The short-term multi-ingredient weight-loss supplementation product did not yield further weightloss for obese women with weight reduction, while it could potentially lead to favorable changes of fat oxidation levels. The effects of the supplementation on weight traits merit large-scale and long-term investigations.

The CLOCK 3111T/C single nucleotide polymorphism and daytime fluctuations of gastric motility in healthy young women: A preliminary study

ABSTRACT The 3111T/C single nucleotide polymorphism (SNP) of Circadian Locomotor Output Cycles Kaput (CLOCK) gene reportedly affects gastric motility before breakfast. It is of interest to know whether this SNP can affect the motility during the daytime. We investigated the association between the CLOCK 3111T/C SNP and several gastric motility parameters during the time period from 8:00 to 20:00 in 34 young women with scheduled meals. There were similar daytime fluctuations in gastric motility before and after the meals between the major (T/T) and minor (T/C) allele carriers. The CLOCK SNP may affect daytime gastric motility less than food stimulation.