Pordenone study: HDL-cholesterol and obesity indexes in the youngBACKGROUND. In 1987, ten years after the first observation, we performed the follow-up of the subjects included in the "Pordenone Study on the precursors of atherosclerosis in childhood". METHODS. The anthropometric, biologic and anamnestic indicators of coronary risk were evaluated. The W.H.O. protocol was always used. 439 (90%) subjects underwent reexamination, (234 males and 205 females between 18 and 26 years). HDL cholesterol, tricipital and subscapular skinfold thickness, weight and height were evaluated. The aim of our study was to find possible correlations between obesity indexes and HDL cholesterol values. RESULTS. We found that HDL cholesterol levels are lower in males compared to females and that differences exist below and over the 80 degrees percentile of BMI. Obese subjects have lower HDL cholesterol levels in both sexes. Females with android obesity (subjects with subscapular skinfold thickness values over 80 degrees percentile) had low HDL cholesterol values. CONCLUSIONS. Because of this inverse correlation between HDL cholesterol and coronary risk, and because young obese generally have low HDL cholesterol levels, we believe that the study of coronary risk factors is also useful starting from this age in overweight subjects. This will be useful for preventive purposes. Particular attention must be given to young girls with android obesity.

Kinetics of biliary secretion of chylomicron remnant cholesterol (esters) in the rat.Chylomicrons labelled with [3H]cholesterol/[3H]cholesterol esters in a ratio of 25.5: 74.5, were rapidly removed from rat serum in vivo, and taken up predominantly by the parenchymal liver cells (88.2%) of the hepatic uptake at 15 min after injection). Lactoferrin reduced the liver uptake of chylomicron remnants by 72%, at 20 min after injection. It appeared that the free cholesterol which is present in the chylomicrons is not readily exchanged within the used time period with other cholesterol pools in the animal. Between 10-60 min after injection of 3H-labelled chylomicrons, cholesterol esters are hydrolysed in the liver. Appearance of radioactivity in bile was rapid and at 3, 24 and 72 h after injection, 13.4%, 44.0% and 70.0%, respectively, of the injected dose appeared in bile, mainly as bile acids (> 90%). Lactoferrin reduced the biliary secretion of radioactivity, especially during the first hour after injection. The total amount of radioactivity recovered was 58.0% of the injected dose at 72 h after injection. After injection of beta-migrating very low-density lipoprotein labelled with [3H]cholesterol/[3H]cholesterol esters in a ratio of 23.5:76.5, the maximum amount of radioactivity secreted in bile was much lower than with chylomicrons (2.6% cf. 5.2% at 1 h after injection), although the kinetics of the initial liver association and cholesterol ester hydrolysis were even more rapid. Biliary accumulation of radioactivity was also lower with 50.5% of the injected dose recovered at 72 h after injection. It can be concluded from these studies that the processing of chylomicron remnant cholesterol components in the liver and the subsequent secretion in the bile mainly as bile acids is very efficient. The efficient liver uptake of chylomicron remnants by the liver remnant receptor is thereby essential to achieve this high percentage of removal, thus protecting against extrahepatic cholesterol (ester) deposition.

Vitamin A and vitamin E statuses of preschool children of socioeconomically disadvantaged families living in the midwestern United States.OBJECTIVE: To determine the vitamin A and vitamin E statuses of socioeconomically disadvantaged preschool American children. DESIGN: Cross-sectional study of preschool children from socioeconomically disadvantaged families. SETTING: Central Iowa, USA. SUBJECTS: A group of 77 apparently healthy children was studied with the following characteristics: 5 mo-6 y; 37 males, 40 females, 56 non-Hispanic Caucasians, 3 Hispanics, 18 Afro-Americans. METHODS: Modified relative dose response (MRDR) test for vitamin A status assessment; serum retinol, alpha-tocopherol, cholesterol, and carotenoids; weight for age. RESULTS: Although the mean weight for age was the 53rd percentile of the NCHS standard, a significant number of children (P = 0.006, chi(2)) were either markedly underweight or overweight. Ratios of 3,4-didehydroretinol to retinol (DR/R) were > 0.030, in 32% of the children. Mean serum retinol, alpha-tocopherol and cholesterol (+/- s.d.) were 1.09 +/- 0.23 microM/L, 16.8 +/- 6.3 microM/L and 4.01 +/- 0.8 microM/L. Three children (3.9%) showed a serum retinol value < 0.7 microM/L. One child with a serum retinol value < 0.7 microM/L and one additional child showed a ratio of alpha-tocopherol to cholesterol < 1.44 mumol/mmol. The mean alpha-tocopherol to cholesterol ratio for the group (4.31 +/- 1.71 mumol/mmol), however, was satisfactory. The only significant (P < or = 0.05) age-related changes were an increase in the serum cholesterol (P = 0.005) and decrease in the alpha-tocopherol to cholesterol ratio (P < 0.005) between the 0-2 y and the 2-4 y groups. Serum cholesterol (P = 0.0165, two-tailed) and lycopene (P = 0.004) concentrations of Afro-Americans were significantly higher than those of Caucasians. Median serum concentrations of alpha-carotene and beta-carotene were lower and, of lycopene higher than those found in children studied in a national survey. Serum carotenoid concentrations generally increased with age. CONCLUSIONS: Larger percentages of underweight and overweight children and a significant degree (32%) of inadequate vitamin A status were found in this group of socioeconomically disadvantaged children. Afro-Americans showed higher serum cholesterol and lycopene concentrations than did Caucasians, but otherwise were nutritionally similar. Age-related changes were small. Of nutritional parameters considered, the vitamin A status of socioeconomically disadvantaged segments of our population clearly needs attention.

The mevalonate pathway during acute tubular injury: selected determinants and consequences.Renal injury evokes tubular cholesterol accumulation, mediated in part by increased HMG CoA reductase (HMGCR) levels. The present study was undertaken to define potential molecular determinants of these changes and to ascertain the relative importance of increased cholesterol production versus mevalonate pathway-driven protein prenylation, on the emergence of the so-called postrenal injury "cytoresistant state." Cultured proximal tubule (HK-2) cells were subjected to Fe or ATP depletion injury, followed 1 to 24 hours later by assessments of: 1) sterol transcription factor expression (SREBP)-1 and -2); 2) HMGCR mRNA levels; and 3) Ras/Rho prenylation. HMGCR mRNA and Ras/Rho prenylation were also assessed after in vivo ischemic and Fe-mediated renal damage. Using specific inhibitors, the relative importance of protein prenylation versus terminal cholesterol synthesis on HK-2 cell susceptibility to injury was also assessed. Acute injury induced HK-2 cell SREBP disruption and reductions in HMGCR mRNA. Renal cortical HMGCR mRNA also fell in response to either in vivo ischemic or Fe-mediated oxidant damage. At 24 hours after in vitro/in vivo injury, a time of cholesterol buildup, no increase in Ras/Rho prenylation was observed. Prenylation inhibitors did not sensitize HK-2 cells to injury. Conversely, squalene synthase (terminal cholesterol synthesis) blockade sensitized HK-2 cells to both Fe and ATP depletion attack. We concluded that: 1) acute tubular cell injury can destroy SREBPs and lower HMGCR mRNA. This suggests that posttranscriptional/translational events are responsible for HMGCR enzyme and cholesterol accumulation after renal damage. 2) Injury-induced cholesterol accumulation appears dissociated from increased protein prenylation. 3) Cholesterol accumulation, per se, seems to be the dominant mechanism by which the mevalonate pathway contributes to the postrenal injury cytoresistant state.

Association of apolipoprotein (Apo)E genotype with plasma apo E levels.The purpose of this study was to investigate the effects of apolipoprotein (apo) E genotype on plasma apo E levels as well as serum total, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, and glucose values in 734 middle-aged and elderly, female and male subjects. Apo E allele frequencies were similar to those reported in other Caucasian populations. After adjustment for medications, alcohol use, smoking, age, and body mass index, apo E genotype was noted to have significant effects on apo E, total cholesterol, LDL cholesterol, and glucose levels in females, and on apo E, LDL cholesterol, and HDL cholesterol levels, as well as the total cholesterol (TC)/HDL cholesterol ratio in males. Female and male subjects with the apo E4 allele had significantly (P<0.05) lower plasma apo E (25 and 15%) and higher LDL cholesterol levels (5 and 2%), while those with the apo E2 allele had significantly (P<0.05) higher apo E (32 and 27%) and lower LDL cholesterol levels (10 and 10%) than the apo E3/3 group. Moreover, female apo E4 carriers had significantly (P<0.05) lower glucose values (11%) than the apo E3/3 group. These data are consistent with the concept that, in addition to the well known effects of apo E genotype on LDL-C values, this locus plays a very significant role in modulating plasma apo E levels.

Effect of fruits of Moringa oleifera on the lipid profile of normal and hypercholesterolaemic rabbits.Rabbits were fed Moringa oleifera (200mg/kg/day, p.o.) or lovastatin (6mg/kg/day, p.o.) in banana pulp along with standard laboratory diet and hypercholesterolaemic diet for 120 days. Moringa oleifera and lovastatin were found to lower the serum cholesterol, phospholipid, triglyceride, VLDL, LDL, cholesterol to phospholipid ratio and atherogenic index, but were found to increase the HDL ratio (HDL/HDL-total cholesterol) as compared to the corresponding control groups. Treatment with M. oleifera or lovastatin in normal rabbits decreased the HDL levels. However, HDL levels were significantly increased or decreased in M. oleifera- or lovastatin-treated hypercholesterolaemic rabbits, respectively. Lovastatin- or M. oleifera-treated hypercholesterolaemic rabbits showed decrease in lipid profile of liver, heart and aorta while similar treatment of normal animals did not produce significant reduction in heart. Moringa oleifera was found to increase the excretion of faecal cholesterol. Thus, the study demonstrates that M. oleifera possesses a hypolipidaemic effect.

Endometrial cancer risk in relation to serum lipids and lipoprotein levels.Blood lipids are useful biochemical indicators for assessing the risk of a number of chronic diseases, particularly those associated with obesity. In a multicenter case-control study that included 256 cases and 185 controls less than 75 years old, we studied the risk of endometrial cancer in relation to serum cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. Contrary to expectation, blood lipids were, in general, lower among cases compared with controls. The effects of low blood lipids, specifically cholesterol and low density lipoprotein cholesterol, were limited to older women (> or = 55 years). Risk of the disease in this subgroup of 177 cases and 110 controls was increased 3-4-fold among those with the lowest cholesterol or low density lipoprotein cholesterol values. For example, after adjustment for age, education, smoking status, obesity, and body fat distribution, the relative risks of endometrial cancer across decreasing quartiles of serum cholesterol were 1.0, 2.5, 2.4, and 4.2 (P for trend < 0.01). We examined blood lipid levels by disease stage. The low lipid values of older cases did not appear to be a consequence of the disease. While we cannot rule out the possibility that hypocholesterolemia is a predisposing factor for endometrial cancer, there is no obvious biological explanation for the inverse association.

Low plasma cholesterol predicts an increased risk of lung cancer in elderly women.BACKGROUND: There have been significant efforts in the United States to lower high cholesterol levels. Studies of men, however, have found a higher total cancer mortality rate at lower levels of plasma cholesterol. Many of these studies have found that lung cancer is more closely associated than other cancers with low cholesterol. Of the studies that include women, none has demonstrated a statistically significant inverse association between low cholesterol and lung cancer. METHODS: We examined the relation between very low plasma cholesterol levels ( < 160 mg/dl) and lung cancer death in an 18-year prospective study of 2,011 men and 2,327 women. RESULTS: After adjusting for age, body mass index, smoking, and education, the relative hazard of lung cancer mortality for those with low cholesterol ( < 160 mg/dl) compared with all other cholesterol levels ( > or = 160 mg/dl) was 1.75 among men (P = 0.28) and 3.29 among women (P = 0.02). Excluding those who died within 5 years of baseline did not change the results. CONCLUSIONS: Both men and women with baseline plasma cholesterol levels < 160 mg/dl were more likely to die of lung cancer. This difference was statistically significant in women. The association could not be explained by occult malignancy, smoking, or socioeconomic status.

Early diet influences hepatic hydroxymethyl glutaryl coenzyme A reductase and 7alpha-hydroxylase mRNA but not low-density lipoprotein receptor mRNA during development.Plasma cholesterol levels increase after birth, and to a greater extent in breast-fed versus formula-fed infants. This increase is believed to be due to the high fat and cholesterol content of the infant diet, but little is known about the effects of early diet on the expression of proteins involved in regulating cholesterol metabolism. This study examined changes in the expression of hepatic proteins regulating cholesterol metabolism during development. Newborn piglets were fed sow milk or one of four formulas for 18 days. The formulas had similar levels of palmitic acid (16:0) as in milk, supplied as palm olein oil with 16:0 esterified predominantly to the sn-1,3 position or as synthesized triglyceride (TG) with 16:0 esterified mainly to the sn-2 position of glycerol, each with no cholesterol (<0.10 mmol/L) or 0.65 mmol/L cholesterol added. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of mRNA levels was used to assess the effects of diet on hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, low-density lipoprotein (LDL) receptor, and 7alpha-hydroxylase (C7H). LDL receptor mRNA levels showed no appreciable difference between milk- and formula-fed piglets. However, the levels of HMG-CoA reductase and C7H mRNA were higher (P < .05) in all formula-fed versus milk-fed piglets, irrespective of the formula TG source or cholesterol content. The lower levels of HMG-CoA reductase and C7H mRNA in milk-fed piglets were accompanied by higher (P < .05) plasma total, high-density lipoprotein (HDL), and apolipoprotein (apo) B-containing cholesterol. These studies show that the levels of hepatic HMG-CoA reductase and C7H mRNA, but probably not LDL receptor mRNA, are altered by early diet.

Overexpression of human lecithin:cholesterol acyltransferase in cholesterol-fed rabbits: LDL metabolism and HDL metabolism are affected in a gene dose-dependent manner.Lecithin:cholesterol acyltransferase (LCAT) is an enzyme well known for its involvement in the intravascular metabolism of high density lipoproteins; however, its role in the regulation of apolipoprotein (apo) B-containing lipoproteins remains elusive. The present study was designed to investigate the metabolic mechanisms responsible for the differential lipoprotein response observed between cholesterol-fed hLCAT transgenic and control rabbits. 131I-labeled HDL apoA-I and 125I-labeled LDL kinetics were assessed in age- and sex-matched groups of rabbits with high (HE), low (LE), or no hLCAT expression after 6 weeks on a 0.3% cholesterol diet. In HE, the mean total cholesterol concentration on this diet, mg/dl (230 +/- 50), was not significantly different from that of either LE (313 +/- 46) or controls (332 +/- 52) due to the elevated level of HDL-C observed in HE (127 +/- 19), as compared with both LE (100 +/- 33) and controls (31 +/- 4). In contrast, the mean nonHDL-C concentration for HE (103 +/- 33) was much lower than that for either LE (213 +/- 39) or controls (301 +/- 55). FPLC analysis of plasma confirmed that HDL was the predominant lipoprotein class in HE on the cholesterol diet, whereas cholesteryl ester-rich, apoB-containing lipoproteins characterized the plasma of LE and, most notably, of controls. In vivo kinetic experiments demonstrated that the differences in HDL levels noted between the three groups were attributable to distinctive rates of apoA-I catabolism, with the mean fractional catabolic rate (FCR, d-1) of apoA-I slowest in HE (0.282 +/- 0.03), followed by LE (0.340 +/- 0.01) and controls (0.496 +/- 0.04). A similar, but opposite, pattern was observed for nonHDL-C levels and LDL metabolism (h-1), such that HE had the lowest nonHDL-C levels with the fastest rate of clearance (0.131 +/- 0.027), followed by LE (0.057 +/- 0.009) and controls (0.031 +/- 0.001). Strong correlations were noted between LCAT activity and both apoA-I (r= -0.868, P < 0.01) and LDL (r = 0.670, P = 0.06) FCR, indicating that LCAT activity played a major role in the mediation of lipoprotein metabolism. In summary, these data are the first to show that LCAT overexpression can regulate both LDL and HDL metabolism in cholesterol-fed rabbits and provide a potential explanation for the prevention of diet-induced atherosclerosis observed in our previous study.