Fat

Am J Clin Nutr. 2003 Aug;78(2):201-8.
Nutrition and genetics: an expanding frontier.
Olson RE. Department of Pediatrics, College of Medicine, University of South Florida, Tampa 33612, USA. rolson@hsc.usf.edu

  The age of molecular biology began in 1953 with the discovery of the structure of DNA. By 1961 the genetic code for the translation of the sequence of bases in DNA to amino acids in proteins was underway, and a model for the genetic regulation of protein synthesis was proposed. My interest in the genetic regulation of nutrient metabolism began in that year during my sabbatical leave in the laboratory of Sir Hans Krebs at Oxford University. In the present article, I describe 2 episodes in my career during which I used genetic concepts to explain a nutritional phenomenon; the first episode occurred before doing the experimental work, and the second occurred after the experimental work was completed. My first brainstorm, which occurred in 1961, was to investigate the hypothesis that all of the fat-soluble vitamins act by the regulation of a cluster of genes. Unfortunately, I selected vitamin K as my model and discovered that it is the only fat-soluble vitamin that does not work in full or in part by the regulation of a set of genes. In 1967 I undertook a second problem, which was to determine the mode of action of polyunsaturated fatty acids in lowering plasma lipid concentrations in humans. We discovered that linoleic acid reduced the storage and enhanced the oxidation of fatty acids. The genetic interpretation of this study has come only recently: polyunsaturated fats have been shown to down-regulate enzymes that accomplish storage of fatty acids and to up-regulate genes that enhance fatty acid oxidation.

PMID: 12885698

  BACKGROUND: Replacing dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) lowers LDL cholesterol, but the underlying mechanisms remain unclear.
  OBJECTIVE: We assessed the effects of replacing dietary SFAs with MUFAs on concentrations and subclass distributions of VLDL, intermediate-density lipoprotein, LDL, and HDL and on VLDL apolipoprotein B kinetics.
  DESIGN: Thirty-five moderately hypercholesterolemic, middle-aged volunteers consumed for 6 wk, in random order, diets containing low (L-MUFA; 7.8% of energy from MUFAs), moderate (M-MUFA; 10.3% from MUFAs), or high (H-MUFA; 13.7% from MUFAs) amounts of MUFAs. Fasting blood samples were taken from all subjects after each intervention. VLDL apolipoprotein B kinetic studies were performed in a subgroup after the L-MUFA and H-MUFA diets.
  RESULTS: Plasma cholesterol concentrations decreased in a dose-dependent manner with increasing intakes of dietary MUFAs. This change was entirely accounted for by reduced LDL cholesterol (-0.20 and -0.49 mmol/L after the M-MUFA and H-MUFA diets, respectively, compared with the concentration after the L-MUFA diet; P for trend < 0.01). Plasma triacylglycerol and HDL cholesterol were not significantly affected by the dietary intervention, nor were the concentrations of VLDL(1) (S(f) 60-400), VLDL(2) (S(f) 20-60), or intermediate-density lipoprotein (S(f) 12-20). Production and catabolic rates for VLDL(1) and VLDL(2) were also unaffected. HDL and LDL subclass distributions were not significantly altered, but as a consequence of the overall LDL lowering, concentrations of atherogenic LDL-III were 25% lower after the H-MUFA diet than after the L-MUFA diet (P = 0.02).
  CONCLUSION: The effects of replacing dietary SFAs with MUFAs on lipoprotein metabolism appear to be almost exclusively limited to the LDL density class.

PMID: 12816770

  Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.

PMID: 12730430

  We have compared lipoprotein metabolism in, and susceptibility to atherosclerosis of, two strains of male Golden Syrian hamster, the Bio F1B hybrid and the dominant spot normal inbred (DSNI) strain. When fed a normal low-fat diet containing approximately 40 g fat and 0.3 g cholesterol/kg, triacylglycerol-rich lipoprotein (chylomicron+VLDL) and HDL-cholesterol were significantly higher (P<0.001) in Bio F1B hamsters than DSNI hamsters. When this diet was supplemented with 150 g coconut oil and either 0.5 or 5.0 g cholesterol/kg, significant differences were seen in response. In particular, the high-cholesterol diet produced significantly greater increases in plasma cholesterol and triacylglycerol in the Bio F1B compared with the DSNI animals (P=0.002 and P<0.001 for cholesterol and triacylglycerol, respectively). This was particularly dramatic in non-fasting animals, suggesting an accumulation of chylomicrons. In a second experiment, animals were fed 150 g coconut oil/kg and 5.0 g cholesterol/kg for 6 and 12 months. Again, the Bio F1B animals showed dramatic increases in plasma cholesterol and triacylglycerol, and this was confirmed as primarily due to a rise in chylomicron concentration. Post-heparin lipoprotein lipase activity was significantly reduced (P<0.001) in the Bio F1B compared with the DSNI animals at 6 months, and virtually absent at 12 months. Bio F1B animals were also shown to develop significantly more (P<0.001) atherosclerosis. These results indicate that, in the Bio F1B hybrid hamster, cholesterol feeding reduces lipoprotein lipase activity, thereby causing the accumulation of chylomicrons that may be associated with their increased susceptibility to atherosclerosis.

PMID: 12628029

  Increased mean platelet volume (MPV) has been suggested as an independent risk factor for acute myocardial infarction and the increased reactivity of large platelets. The aim of this study was to investigate the correlation between platelet phospholipid (PL) PUFA composition and MPV in 139 free-living healthy men ages 20-55 yr (vegans, n = 18; ovolacto vegetarians, n = 43; moderate meat-eaters, n = 60; and high meateaters, n = 18). Each subject completed a semiquantitative Food Frequency Questionnaire and gave a blood sample. Platelet PL FA composition and MPV were determined by standard methods. MPV was significantly greater in the vegans than in the ovolacto vegetarian, moderate, or high meat-eater groups (P < 0.01). Both vegan and ovolacto vegetarian groups had significantly higher platelet PL 18:2n-6 and 22:4n-6, and lower 20:5n-3 and 22:6n-3 compared with the moderate and high meat-eater groups. The vegans demonstrated a significant reduction in 20:4n-6 and 22:5n-3 compared with the ovolacto vegetarian, high meat-eater, and moderate meat-eater groups. Bivariate analysis results showed that MPV was significantly positively correlated with platelet PL 18:2n-6 (P = 0.048) and negatively correlated with 20:3n-6 (P = 0.02), 20:5n-3 (P = 0.005), and 22:5n-3 (P< 0.0001), respectively. In a multiple linear regression analysis, after controlling for potential confounding factors such as dietary group, age, exercise, body mass index, and dietary polyunsaturated and saturated fat, cholesterol, carbohydrate, and fiber intake, the MPV was still strongly negatively correlated with platelet PL 20:3n-6 (P = 0.003) and 22:5n-3 (P = 0.001). The present data suggest that 22:5n-3 and 20:3n-6 may play a role in the structural function of the platelet membrane.

PMID: 12458626

  Green vegetable consumption has long been considered to have health benefits mainly due to the vitamins, minerals and phytonutrients (such as vitamin C, folate, antioxidants etc) contained in a vegetable-rich diet. Additionally, green vegetables are known to contain a relatively high proportion of omega-3 polyunsaturated fatty acids (PUFAs), primarily in the form of alpha-linolenic acid (18:3n-3). However, there are no data available on the fatty acid composition and concentration of green vegetables commonly consumed in Australia. The present study determined the fatty acid content of 11 green vegetables that are commonly available in Australia. The total fatty acid concentrations of the vegetables under study ranged from 44 mg/100 g wet weight in Chinese cabbage to 372 mg/100 g in watercress. There were three PUFAs in all vegetables analyzed; these were 16:3n-3, 18:2n-6, and 18:3n-3 fatty acids. Sample vegetables contained significant quantities of 16:3n-3 and 18:3n-3, ranging from 23 to 225 mg/100 g. Watercress and mint contained the highest amounts of 16:3n-3 and 18:3n-3, and parsley had the highest amount of 18:2n-6 in both percentage composition and concentration. Mint had the highest concentration of 18:3n-3 with a value of 195 mg/100 g, while watercress contained the highest concentration of 16:3n-3 at 45 mg/100 g. All 11 green vegetables contained a high proportion of PUFAs, ranging from 59 to 72% of total fatty acids. The omega-3 PUFA composition ranged from 40 to 62% of total fatty acids. Monounsaturated fatty acid composition was less than 6% of total fatty acids. The proportion of saturated fatty acids ranged from 21% in watercress and mint to 32% of total fatty acids in Brussels sprouts. No eicosapentaenoic and docosahexaenoic acids were detected in any of the samples. Consumption of green vegetables could contribute to 18:3n-3 PUFA intake, especially for vegetarian populations.

PMID: 11582857

  We sought to examine the effects of plasma lipids, especially in remnants after a fat meal, on systemic arterial compliance (SAC), a newly recognized cardiovascular risk factor.
  BACKGROUND: Post-prandial remnants correlate with coronary heart disease events through mechanisms that may include vascular dysfunction, although the effect on SAC has not been studied.
  METHODS: Systemic arterial compliance was measured non-invasively over 6 h after a fat meal in 16 subjects with varying plasma triglyceride levels. Changes were related to rises in plasma lipids and remnant lipids. Systemic arterial compliance was measured in 20 subjects after a control low-fat meal.
  RESULTS: The fat meal induced increments in plasma triglyceride and remnant cholesterol and triglyceride (respectively +54%, 50% and 290% at 3 h, analysis of variance <0.001). Systemic arterial compliance fell at 3 h and 6 h by 25% and 27% (analysis of variance <0.001). Baseline SAC correlated significantly with all lipid concentrations at 0, 3 h and 6 h, but only with triglyceride on stepwise regression analysis. The SAC response to the low-fat meal was very small and not significant.
  CONCLUSIONS: This is the first demonstration of SAC becoming impaired after a fat meal. Remnant lipids and plasma total triglyceride appeared to contribute to the fall in SAC.

PMID: 11401134

  Impaired flow-mediated vasodilation in large arteries is an expression of endothelial dysfunction and an established marker of early atherosclerosis. Post-prandial lipemia can induce an impairment of the endothelial function. The aim of our study was to evaluate the effects of post-prandial phase on flow-mediated vasodilation in a group of ten young (23 +/- 2 years) healthy men without cardiovascular risk factors, who underwent an oral fat-loading test. Flow-mediated vasodilation of the brachial artery and serum lipid profile were assessed under fasting conditions and 2, 4, 6 and 8 h after a high-fat meal. Triglycerides increased from 0.6 +/- 0.2 fasting to 1.1 +/- 0.5 and 1.3 +/-0.6 mmol/l at the 2nd and 4th hour (both P < 0.01), and decreased thereafter. Flow-mediated vasodilation fell significantly from 14.5 +/- 6.6% fasting to 3.5 +/- 1.5% and 4.0 +/- 2.2% at the 2nd and 4th hour (both P < 0.01), and returned to the basal values at the 6th and 8th hour. A strong inverse correlation was observed between the area under the incremental curve of post-prandial triglycerides (i.e. after subtraction of baseline triglycerides) and the area under the decremental curve of post-prandial flow-mediated vasodilation (r = -0.70, P = 0.025). No association was found between post-prandial vasodilation changes and fasting triglycerides, other lipid parameters or insulin. We conclude that a transient post-prandial impairment in brachial artery flow-mediated vasodilation is evident in young healthy men after a high-fat meal, and is closely associated with triglyceride levels. These data provide support for a role of post-prandial phase in vascular regulation in young healthy subjects.

PMID: 11164429

  Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p<0.01). LDL/HDL ratio remained unchanged. Thus, in healthy premenopausal women, a low-fat vegetarian diet led to rapid and sizable reductions in serum total, LDL, and HDL cholesterol concentrations.

Trial PMID: 10760336

  OBJECTIVE: To study, if there are differences in the fatty acid composition of low-density lipoprotein (LDL) in people eating three different long-standing habitual diets: vegetarian, high fish intake, or high saturated fat (milk fat) diet as a control group, and to study if these differences influence the oxidation susceptibility of LDL.
  DESIGN: Cross-sectional study using blood samples and a validated dietary frequency questionnaire with illustrations. Setting: Helsinki University Central Hospital, Finland.
  SUBJECTS: The effect of three different types of long-standing diets of different fatty acid content (a strict vegetarian diet, n=11; a high fish intake diet, n=9; and a high saturated fat (milk fat) diet, controls, n=7) on the serum and LDL fatty acid content, and on the susceptibility of LDL to oxidation in vitro, was studied in healthy normocholesterolemic volunteers who had been on these diets for years. Oxidation of LDL was carried out by using CuSO4 as a pro-oxidant.
  RESULTS: There were no statistically significant differences in the serum lipids or lipoproteins, though the vegetarian group exhibited lowest mean values of total, high-density lipoprotein (HDL) and LDL cholesterol levels. Both the serum and LDL eicosapentaenoic, docosapentaenoic and docosahexaenoic acid proportions were highest in the fish and lowest in the vegetarian groups. Linoleic acid was highest among the vegetarians. In the fish group, the vitamin A concentration in serum was higher than in vegetarians and controls and beta-carotene lower than in controls, but in alpha-tocopherol, or lycopene concentrations there were no statistically significant differences. The lag phase of LDL oxidation was shortest (116 min) in the fish group and longest (165 min) in the vegetarian group, and the control group was between them (129 min). The mean oxidation percentage after 2.5 h of copper-induced oxidation was highest (44%) in the fish group and lowest (22%) in the vegetarian group and intermediate (31%) in the control group.
  CONCLUSION: Long-term dietary habits predict the fatty acid composition of serum and LDL, and influence the susceptibility of LDL to oxidation. In the fish group with the highest content of omega-3 fatty acids in LDL, the oxidation susceptibility of LDL was highest. In the vegetarian group with less omega-3 fatty acids in LDL, the LDL was more resistant to oxidation.
  SPONSORSHIP: Helsinki University Central Hospital.

PMID: 10556987

  The trans fatty acids produced by partially hydrogenating vegetable oils may cause colorectal neoplasia by interfering with cell membrane function or eicosanoid synthesis. This possibility provides a rationale for looking at the relation between colorectal adenomatous polyps and consumption of foods containing partially hydrogenated vegetable oils (PHVOs). A total of 516 cases and 551 controls who underwent screening sigmoidoscopy from 1991-1993 were recruited from a prepaid Los Angeles health plan. Subjects were interviewed and given a self-administered food frequency questionnaire. Food items containing PHVOs were divided into four groups characterized by principal ingredients and preparation methods: sweetened baked goods, candy bars, oils and condiments, and french fries and chips. After adjusting for age, sex, physical activity, body mass index, smoking, total energy, and red meat and vegetable intake, there was a positive association between polyps and sweetened baked goods [350+ versus <50 kcal/day (odds ratio, 2.1; 95% confidence interval, 1.3-3.5)]. No association was found with the other food groups after adjustment for dietary and nondietary covariates. Neither was total dietary trans fatty acid associated with adenomas after adjustment for sweetened baked goods and other covariates. These results do not support the hypothesis that eating foods containing PHVOs increases the risk of colorectal adenomas, but they are consistent with the hypothesis that foods high in fat and sugar and low in fiber and correlated micronutrients increase the risk of adenomas.

PMID: 10385142

  BACKGROUND: Individuals with obesity, in particular those with intra-abdominal visceral fat accumulation, are known to have various complications, such as hyperlipidaemia, impaired glucose tolerance, hyperinsulinaemia and hypertension, leading to the development of coronary heart disease. Post-prandial hyperlipidaemia has repeatedly been shown to be an independent risk factor for coronary heart disease. The aim of the present study was to investigate post-prandial lipoprotein metabolism in subjects with excessive visceral fat accumulation.
  MATERIALS AND METHODS: Eighty-three patients (52 men, 31 women) [average age 48 +/- 14 years; mean body mass index (BMI) 25 +/- 5 kg m-2] were recruited to the study. Visceral (or subcutaneous) fat accumulation was analysed as areas of fat deposition by computerized tomography at the umbilicus level. After a 12-h overnight fast, oral vitamin A and a fatty meal (40 g m-2 fresh cream containing 50 000 units m-2 vitamin A) were administered to these subjects. The concentration of retinyl palmitate (RP) was measured by high-performance liquid chromatography.
  RESULTS: The visceral fat area (V) was positively correlated with plasma triglyceride (TG) 0, 2, 4 and 6 h after fat loading and with plasma RP 0, 4 and 6 h after fat loading. The BMI did not show any correlation with plasma TG and RP at any point. The visceral fat area was positively correlated with the RP area under the curve (AUC) in the serum from the subjects [V vs. RP AUC: n = 83, r = 0.327, P = 0.013]. The BMI of the subjects did not show any correlation with the RP AUC (r = 0.021, P = 0.85).
  CONCLUSION: These results suggest that post-prandial lipid metabolism is impaired in subjects with intra-abdominal visceral fat accumulation, irrespective of BMI, leading to the development and progression of coronary atherosclerosis.

PMID: 10231342

  Nineteen young male normolipidemic volunteers sequentially consumed three test meals consisting of cream only, sucrose only, or cream with sucrose. These oral fat-tolerance tests showed an amplification of the postprandial excursion of serum triglyceride and cholesterol concentrations when sucrose was included in a lipid-rich meal compared with both the cream-only meal and the sucrose-only meal. The triglyceride concentration increase occurred only in the late postprandial phase whereas the cholesterol concentration was increased for the entire 8 h studied. The increased triglyceride and cholesterol concentrations in the triglyceride-rich lipoprotein (TRL) fraction accounted for most of the increase. The clearance of an intravenous lipid emulsion was measured before and 2 and 4 h after a sucrose meal. The two postprandial clearance rates were 34% slower than the fasting value. These data indicate that sucrose-induced postprandial hypertriglyceridemia may be induced by an inhibition of the clearance of triglyceride. The slower rate of lipolysis may cause the accumulation of cholesterol in TRL.

PMID: 8147330

  Dietary cholesterol appears to be associated with long-term cardiovascular risk even after its potential for cholesterol elevation has been accounted for, but the mechanism is unknown. Our aim in this study was to determine the postprandial lipoprotein changes after a high-cholesterol load (equal to about three eggs) eaten with a low-fat meal by three phenotypic groups [normal, high low-density-lipoprotein (LDL)-cholesterol concentration, and high plasma triacylglycerol concentration] and compare them with the changes seen after a low-fat meal without cholesterol. Twenty-one normolipidemic and hyperlipidemic men and women were studied on two occasions after a single meal, one containing 19 g fat and 700 mg cholesterol, the other containing a similar amount of fat but no cholesterol. Their plasma intermediate-density lipoproteins (IDLs), LDLs, and high-density lipoproteins (HDLs) were separated by isopycnic ultracentrifugation. The addition of 700 mg cholesterol to the meal increased the amount of cholesterol and triacylglycerol in the large triacylglycerol-rich lipoproteins (Sf > 1000), particularly in the hypertriacylglycerolemic group (P = 0.02, fat meal compared with fat and cholesterol meal). In the hypertriacylglycerolemic group the normal fall in HDL cholesterol after a fat meal was reduced by 87% (P = 0.02, fat meal compared with fat and cholesterol meal). Both of these changes may be atherogenic. There was no increase in any candidate atherogenic particle (e.g., small very-low-density lipoprotein, IDL, or LDL) with the acute dietary cholesterol load. Thus, dietary cholesterol does not acutely alter postprandial lipoproteins to produce a more atherogenic profile except possibly in hypertriacylglycerolemic subjects.

PMID: 8780346

  The purpose of the study was to examine the effect of exercise timing on postprandial lipemia responses. Subjects were 21 recreationally trained men (ages 27 +/- 1.7 yr). Each subject performed four trials: 1) Control (fat meal only), 2) Post (exercise 1 h after a fat meal), 3) 1 h-Pre (exercise 1 h before a fat meal), and 4) 12 h-Pre (exercise 12 h before a fat meal). In each trial, subjects had a standard fat meal to induce postprandial hypertriglyceridemia. Blood samples were taken at 0 h (immediately before the fat meal) and at 2, 4, 6, 8, and 24 h after the meal. In the exercise trials, each subject exercised at 60% of maximal O2 consumption for 1 h. The results indicated that triglyceride area under the curve scores in premeal-exercise trials were lower (P < 0. 05) than those in Post and Control. At 24 h, total high-density lipoprotein (HDL)-cholesterol in the premeal-exercise trials was higher (P < 0.05) than that at 0 h, whereas total HDL-cholesterol was not changed in Control and Post. At 24 h, HDL subtype 2-cholesterol was higher (P < 0.05) in the premeal-exercise trials than in Control, which did not differ from Post. These results suggest that exercising before a fat meal may have a beneficial effect on the triglyceride response and HDL metabolism, which may blunt atherosclerotic process induced by the fat meal.

PMID: 9760349

  OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function.
  BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown.
  METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat.
  RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function.
  CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.

PMID: 10091835