Saturated fat in the diet of Spanish children: relationship with anthropometric, alimentary, nutritional and lipid profiles

OBJECTIVE: To compare the anthropometric, alimentary, nutritional and lipid profiles and global diet quality of Spanish children according to saturated fat intake. DESIGN: This was a cross-sectional study. Food data were collected using a food-frequency questionnaire. SUBJECTS AND METHODS: The sample included 1112 children of both sexes, aged between 6 and 7 years, selected by means of random cluster sampling in schools. The plasma lipid profile included measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (apoA1) and apolipoprotein B (apoB). Global diet quality was evaluated by the Dietary Variety Index (DVI) and the Healthy Eating Index (HEI). RESULTS: Energy intake, DVI and HEI of children from the lower quartile of saturated fat intake (LL) were higher (P<001) than in the remaining children (UL). However, there were no significant differences in average height or weight between groups. The UL children had lower intakes of meat, fish, vegetables, fruits and olive oil and a higher intake of dairy products (P<0.001). The intakes of fibre, vitamins C, D, B6, E and folic acid were higher in the LL children, who had lower intakes of vitamin A and calcium. The ratios LDL-C/HDL-C and apoB/apoA1 were lower (P=0.04) in the LL children (1.87 and 0.52, respectively) than in the UL children (2.02 and 0.54, respectively). CONCLUSIONS: The growth rate of children does not seem to be affected by the level of saturated fat intake. Furthermore, at the levels of intake observed in this study, diets with less saturated fat are associated with better alimentary, nutritional and plasma lipid profiles.This study was partly funded by grants from the Fondo deInvestigacio ́n Sanitaria (FIS 020994, FIS02/3104) and theMinisterio Agricultura Pesca y Alimentacio ́n. We thankAlexander G Borun for manuscript revisionS

Role of cholesterol metabolism in the anticancer pharmacology of selective estrogen receptor modulators

Selective estrogen receptor modulators (SERMs) are a class of compounds that bind to estrogen receptors (ERs) and possess estrogen agonist or antagonist actions in different tissues. As such, they are widely used drugs. For instance, tamoxifen, the most prescribed SERM, is used to treat ERα-positive breast cancer. Aside from their therapeutic targets, SERMs have the capacity to broadly affect cellular cholesterol metabolism and handling, mainly through ER-independent mechanisms. Cholesterol metabolism reprogramming is crucial to meet the needs of cancer cells, and different key processes involved in cholesterol homeostasis have been associated with cancer progression. Therefore, the effects of SERMs on cholesterol homeostasis may be relevant to carcinogenesis, either by contributing to the anticancer efficacy of these compounds or, conversely, by promoting resistance to treatment. Understanding these aspects of SERMs actions could help to design more efficacious therapies. Herein we review the effects of SERMs on cellular cholesterol metabolism and handling and discuss their potential in anticancer pharmacology

Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17&#x3B2;-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages

Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability

White adipose tissue (WAT) produces lactate in significant amount from circulating glucose, especially in obesity;Under normoxia, 3T3L1 cells secrete large quantities of lactate to the medium, again at the expense of glucose and proportionally to its levels. Most of the glucose was converted to lactate with only part of it being used to synthesize fat. Cultured adipocytes were largely anaerobic, but this was not a Warburg-like process. It is speculated that the massive production of lactate, is a process of defense of the adipocyte, used to dispose of excess glucose. This way, the adipocyte exports glucose carbon (and reduces the problem of excess substrate availability) to the liver, but the process may be also a mechanism of short-term control of hyperglycemia. The in vivo data obtained from adipose tissue of male rats agree with this interpretation