Critical role of neutral cholesteryl ester hydrolase 1 in cholesteryl ester hydrolysis in murine macrophages.

Hydrolysis of intracellular cholesteryl ester (CE) is the rate-limiting step in the efflux of cholesterol from macrophage foam cells. In mouse peritoneal macrophages (MPMs), this process is thought to involve several enzymes: hormone-sensitive lipase (Lipe), carboxylesterase 3 (Ces3), neutral CE hydrolase 1 (Nceh1). However, there is some disagreement over the relative contributions of these enzymes. To solve this problem, we first compared the abilities of several compounds to inhibit the hydrolysis of CE in cells overexpressing Lipe, Ces3, or Nceh1. Cells overexpressing Ces3 had negligible neutral CE hydrolase activity. We next examined the effects of these inhibitors on the hydrolysis of CE and subsequent cholesterol trafficking in MPMs. CE accumulation was increased by a selective inhibitor of Nceh1, paraoxon, and two nonselective inhibitors of Nceh1, (+)-AS115 and (-)-AS115, but not by two Lipe-selective inhibitors, orlistat and 76-0079. Paraoxon inhibited cholesterol efflux to apoA-I or HDL, while 76-0079 did not. These results suggest that Nceh1 plays a dominant role over Lipe in the hydrolysis of CE and subsequent cholesterol efflux in MPMs.

Prevalence of Type 2 Diabetes in Mongolia: Results from Population-Based Survey Compared with 1999 Study.

Purpose: The burden of diabetes in Mongolia has risen tremendously over the last three decades, and an individually tracked, national registry of diabetes is lacking. Therefore, we aim to investigate diabetes prevalence in Mongolia and analyze some associated factors. Materials and Methods: A cross-sectional, nationally representative, population-based survey was carried out in Mongolia. We recruited participants from randomly selected six different clusters for the required 3113 ± 311 sample size. We collected detailed demographics, diabetes condition and medications, anthropometric measurements, body composition, and glucose profiles. Oral glucose tolerance tests were used to diagnose diabetes using the International Diabetes Federation algorithm. Chi-square and multinomial logistic regression tests were used to determine associated factors. Age-standardized prevalence rates were estimated. Results: We recruited 3272 participants in the study between June and October 2019. Crude prevalence rates for prediabetes and diabetes were 10.8% (95% CI; 9.8-11.9) and 11.2% (95% CI; 10.1-12.3), respectively. Sixty-one adults were newly diagnosed with diabetes. Age-standardized prediabetes and diabetes prevalence rates were 9.8% (95% CI; 8.5-11.1) and 10.0% (95% CI; 8.7-11.3) among adults 30 or older. Higher BMI, central obesity, diabetes inheritance, sedentary habitus, and hypertension are significantly associated with diabetes in adjusted analysis for sex and age group. Conclusion: The prevalence of diabetes has increased at least threefold since 1999 in Mongolia. In addition, numerous modifiable risk factors were associated with diabetes. Therefore, future investigations and programs should focus on combating obesity and sedentary lifestyles and propose dietary recommendations in the context of expanding diabetes in Mongolia.