Although the global prevalence of both the overweight and obese is on the rise, there are variations among regions or countries, and sexes. Approximately half or more than half of the population are overweight/obese defined as body mass index ≥25 kg/m2in the Americas (61.1%), Europe (54.8%), and Eastern Mediterranean (46.0%) according to the World Health Organization, while a much lower prevalence is observed in Africa (26.9%), South-East Asia (13.7%), and the Western Pacific (25.4%). Females are more likely to be overweight/obese in the Eastern Mediterranean, Africa, South-East Asia and the majority of countries in the Americas and Western Pacific but not in the most of the countries in Europe. These region-sex-ethnicity differences in prevalence may be a clue to the causes of the obesity epidemic. Epidemiological studies done in the USA, Europe, and Asia found that higher BMI was significantly associated with increased incidence of coronary artery disease (CAD) and ischemic stroke, but the association with hemorrhagic stroke incidence was not always consistent. The association of BMI with CAD and ischemic stroke was generally independent of known mediators, which would indicate the importance of controlling or preventing overweight/obesity for the prevention of cardiovascular disease. (Circ J 2014; 78: 2807–2818)

Changing trends in the prevalence of H. pylori infection in the general population over time are thought to be the main driving force behind the declining gastric cancer mortality in Japan. However, whether the prevalence of H. pylori infection itself shows a birth-cohort pattern needs to be corroborated. We performed a systematic review of studies that reported the prevalence of H. pylori infection among Japanese individuals. Meta-regression was conducted in the framework of a generalized additive mixed model (GAMM) to account for heterogeneity in the prevalence of H. pylori infection as a function of birth year. The prevalence of H. pylori infection confirmed a clear birth cohort pattern: the predicted prevalence (%, 95% CI) was 60.9 (56.3–65.4), 65.9 (63.9–67.9), 67.4 (66.0–68.7), 64.1 (63.1–65.1), 59.1 (58.2–60.0), 49.1 (49.0–49.2), 34.9 (34.0–35.8), 24.6 (23.5–25.8), 15.6 (14.0–17.3), and 6.6 (4.8–8.9) among those who were born in the year 1910, 1920, 1930, 1940, 1950, 1960, 1970, 1980, 1990, and 2000, respectively. The present study demonstrated a clear birth-cohort pattern of H. pylori infection in the Japanese population. The decreased prevalence of H. pylori infection in successive generations should be weighed in future gastric cancer control programs.

Jumonji D3 (JMJD3) histone demethylase epigenetically regulates development and differentiation, immunity, and tumorigenesis by demethylating a gene repression histone mark, H3K27-me3, but a role for JMJD3 in metabolic regulation has not been described. SIRT1 deacetylase maintains energy balance during fasting by directly activating both hepatic gluconeogenic and mitochondrial fatty acid β-oxidation genes, but the underlying epigenetic and gene-specific mechanisms remain unclear. In this study, JMJD3 was identified unexpectedly as a gene-specific transcriptional partner of SIRT1 and epigenetically activated mitochondrial β-oxidation, but not gluconeogenic, genes during fasting. Mechanistically, JMJD3, together with SIRT1 and the nuclear receptor PPARα, formed a positive autoregulatory loop upon fasting-activated PKA signaling and epigenetically activated β-oxidation–promoting genes, including Fgf21, Cpt1a, and Mcad. Liver-specific downregulation of JMJD3 resulted in intrinsic defects in β-oxidation, which contributed to hepatosteatosis as well as glucose and insulin intolerance. Remarkably, the lipid-lowering effects by JMJD3 or SIRT1 in diet-induced obese mice were mutually interdependent. JMJD3 histone demethylase may serve as an epigenetic drug target for obesity, hepatosteatosis, and type 2 diabetes that allows selective lowering of lipid levels without increasing glucose levels.

The X chromosome–encoded histone demethylase UTX (also known as KDM6A) mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish transcriptionally permissive chromatin. Loss of UTX in female mice is embryonic lethal. Unexpectedly, male UTX-null mice escape embryonic lethality due to expression of UTY, a paralog that lacks H3K27 demethylase activity, suggesting an enzyme-independent role for UTX in development and thereby challenging the need for active H3K27 demethylation in vivo. However, the requirement for active H3K27 demethylation in stem cell–mediated tissue regeneration remains untested. Here, we employed an inducible mouse KO that specifically ablates Utx in satellite cells (SCs) and demonstrated that active H3K27 demethylation is necessary for muscle regeneration. Loss of UTX in SCs blocked myofiber regeneration in both male and female mice. Furthermore, we demonstrated that UTX mediates muscle regeneration through its H3K27 demethylase activity, as loss of demethylase activity either by chemical inhibition or knock-in of demethylase-dead UTX resulted in defective muscle repair. Mechanistically, dissection of the muscle regenerative process revealed that the demethylase activity of UTX is required for expression of the transcription factor myogenin, which in turn drives differentiation of muscle progenitors. Thus, we have identified a critical role for the enzymatic activity of UTX in activating muscle-specific gene expression during myofiber regeneration and have revealed a physiological role for active H3K27 demethylation in vivo.

Skipping breakfast has been suspected as a risk factor for type 2 diabetes (T2DM), but the associations are not entirely consistent across ethnicities or sexes, and the issue has not been adequately addressed in the Japanese population. We followed 4631 participants (3600 men and 1031 women) in a work-site cohort of participants aged 35-66 years in 2002 through 2011 for T2DM development. Frequency of eating breakfast was self-reported and was subsequently dichotomized to breakfast skippers, who eat breakfast 3-5 times/week or less, and to eaters. Cox proportional hazards models were used to adjust for potential confounding factors, including dietary factors, smoking and other lifestyles, body mass index (BMI), and fasting blood glucose (FBG) at baseline. During 8.9 years of follow-up, 285 T2DM cases (231 men and 54 women) developed. Compared to participants who reported eating breakfast every day, maximally-adjusted hazard ratios and 95% confidence intervals (CI) of those with the frequency of almost every day and 3-5, 1-2, and 0 days/week were: 1.06 (95% CI, 0.73-1.53), 2.07 (95% CI, 1.20-3.56), 1.37 (95% CI, 0.82-2.29), and 2.12 (95% CI, 1.19-3.76), respectively. In a dichotomized analysis, breakfast skipping was positively associated with T2DM incidence (maximally-adjusted hazard ratio 1.73; 95% CI, 1.24-2.42). The positive associations were found in both men and women, current and non-current smokers, normal weight and overweight (BMI ≥ 25 kg/m(2)), and normal glycemic status and impaired fasting glycemic status (FBG 110 to 0.05). The present study in middle-aged Japanese men and women suggests that skipping breakfast may increase the risk of T2DM independent of lifestyles and baseline levels of BMI and FBG.