Background Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. Methods We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. Results In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range — by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. Conclusions Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.
Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial–mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.
Soy food intake has been shown to have beneficial effects on cardiovascular disease risk factors. Data directly linking soy food intake to clinical outcomes of cardiovascular disease, however, are sparse. We examined the relationship between soy food intake and incidence of coronary heart disease (CHD) among participants in the Shanghai Women's Health Study, a population-based prospective cohort study of approximately 75000 Chinese women aged 40-70 y at the baseline survey that was conducted from 1997 to 2000. Included in this study were 64915 women without previously diagnosed CHD, stroke, cancer and diabetes at baseline. Information on usual intake of soy foods was obtained at baseline through an in-person interview using a validated food-frequency questionnaire. Cohort members were followed biennially through in-person interviews. After a mean of 2.5 y (162277 person-years) of follow-up, 62 incident cases of CHD (43 nonfatal myocardial infarctions and 19 CHD deaths) were documented. There was a clear monotonic dose-response relationship between soy food intake and risk of total CHD (P for trend = 0.003) with an adjusted relative risk (RR) of 0.25 (95% CI, 0.10-0.63) observed for women in the highest vs. the lowest quartile of total soy protein intake. The inverse association was more pronounced for nonfatal myocardial infarction (RR = 0.14; 95% CI, 0.04-0.48 for the highest vs. the lowest quartile of intake; P for trend = 0.001). This study provides, for the first time, direct evidence that soy food consumption may reduce the risk of CHD in women.
Soy food consumption may reduce the risk of fracture in postmenopausal women, particularly among those in the early years following menopause.
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