- Email: [email protected]
Hypocholesterolemia and malignancy
Wednesday 12 October 1994: Poster Abstracts Lipoproteins
compound heterozygous HL deficiency. However, the metabolic function of HL in lipoprotein metabolism is still not clear. We identified a patient with homozygous HL deficiency from 500 unrelated hypertriglyceridernic patients by measuring the HL immunomactive mass in postheparin plasma (PHP) using sandwith EIA (.J Lipid Res 1990; 31: 1911-1924) followed by analysis of HL gene abnormalities using PCR-SSCP and direct sequencing methods. The patient had a missense mutation in exon 3 of the HL gene, leading to no detectable mass in PHP. This was confirmed
211
by expressing the mutant HL in COS-1 cells. The patient’s serum was clear despite a TG of 320 mg/dl, characteristic of type N hyperlipoproteinemia. Analysis of fractionated lipoproteins showed an accumulation of IDL, TG-rich LDL and HDL, whereas VLDL was within the normal range. Absence of B-VLDL was confirmed by agarose electrophoresis. These results indicate that HL is primarily involved in the catabolism of TG in relatively small lipoproteins such as IDL, LDL and HDL.
LIPOPROTEINS pij
Hypocholesterolemia and malignancy Marsh S’, h&&&A’, Leviov M2 Mashiach T3, Wolfowitz El, Cohen E2, Robinson E2, Brook JG’, tDept. ofMed. ‘D’and Lipid Unif, ‘Dept. of Oncol. and 3Dept. of Quality Control, Technion, Faculty of Med., Haifa, Israel, 31096
The objective of this study was to determine the relationship between hypocholesterolemia and malignancy. TC and LDL-C values were compared to controls, and correlations made between patients with localized as opposed to disseminated disease. Patients referred for initial oncological treatment from October 1992 to February 1994 were randomly included. The control group comprised healthy individuals undergoing a routine check-up. This group was sex and age matched with respect to the patients. There were 266 patients (mean age 60f 14) comprising 110 men and 156 women. Controls comprised 262 subjects (mean age 56f 10) including 139 men and 123 women. The values of TC and LDL-C were 221+ 50 and 174 zk46 respectively, in the patient population, and these values did not differ from the controls. Among subjects with cancer, the levels of TC were lower in those with metastatic disease (202 f 50) than in those with localized disease (230 f 49) (P = 0.0001). Differences in LDL-C values were also significant (155 & 42 vs 177 -+42) (P = 0.015). Patients with metastatic disease had significantly lower values of cholesterol (P = 0.008) and LDL-C (P = 0.019) than controls. Furthermore, cholesterol levels below 175 mg/dl were found in 19/55 (35%) patients with extensive disease and only 39/263 (15%) of the control subjects (P = 0.003). In patients with cancer, cholesterol and LDL values were higher for women (229 f 53 and 182+51 respectively) than for men (21Ort43 and 164*36 respectively). Colon cancer and Iymphoma were associated with significantly lower levels of cholesterol than control patients. In conclusion, metastatic tumor is associated with significantly lower cholesterol levels, which could be secondary to overutilization of cholesterol by an increased population of cancer cells in patients with extensive disease. 11171
Influence of puberty, body composition and diet on IipopFteins n KM Willows N2, Grimston S, Hanley D2, ‘Dept. of
Pediatrics, Unk. of Manitoba, Winnipeg, MB. Canada, R3E 022; ‘Dept. of Med., Univ. of Calgary
To examine the influences of sexual maturation, body composition, and diet on serum lipoproteins, 109 healthy adolescents (58 female, 51 male) participating in competitive athletics were subdivided into 3 groups according to Tanner pubertal stage (Tl, T2/3, T4/5). A 6-day diet history, body composition and fasting lipoproteins, apolipoproteins and sex steroids were measured. As puberty progressed, lower TC (P = 0.001). apolipoproteins (P = 0.02) and LDL-C (P = O.OOl),and higher TG (P = 0.03) were seen in both sexes. Lower apolipoprotein A (P = 0.001) and HDLC (P = 0.001) were seen in males only. In late puberty, males had lower levels of apo A and HDL-C (P = 0.001) than females. Fat consumption as a percentage of calories (P = 0.02) decreased with
pubertal progression in both sexes. Females in all pubertal groups demonstrated increased adiposity compared to males in that their sum of 10 skinfolds and the amount of fat/muscle (FAT/MUS) were greater. In males, multiple regression analysis showed that advancing pubertal stage is a significant predictor of apo A (r = -0.60), TC (r = -0.53) and LDL-C (r = -0.40). Estradiol was a predictor of the TCHDL ratio (r = +0.34) and TG (r = +0.57). In females, serum testosterone was a significant predictor of apo B (r = -0.26) and TCXIDL (r = -0.40). FAT/MUS predicted TG (r = +0.29) and HDL-C (r = 4.35) and the waist/hip ratio, apo B (r = +0.36) and HDL-C (r=+O.29). The percentage of non-dairy fat consumed predicted apo B (r = -0.27) and percentage of dairy fat, HDL-C (r = 4.34). No variables correlated with apolipoprotein(a) levels in males or females. In sununary, sexual maturation and increased endogenous estrogen levels have significant impact on lipoproteins in adolescent males. Body composition and diet are more important predictive variables among adolescent females. Investigation of cholesterolemic responses to dietary amino acids and the mechanisms involved Kurowska EM, Carroll KK, Dept. of Biochem., Centre for Human
11181
Nutrition, Univ. of Western Ontario, London, ON, Canada N6A XI
Casein and other animal proteins are known to be more hypercholesterolemic than soy protein and other plant proteins when fed to rabbits in low-fat, cholesterol-free, semipurified diets. Studies in which a casein amino acid mixture or modifications of that mixture were fed to rabbits in the same type of diet indicated that the above differences are related to the higher content of some essential amino acids (especially Lys and Met) and the lower content of Arg and non-essential amino acids in casein than in plant proteins. The hypercholesterolemia produced by high levels of casein amino acids was not accompanied by changes in hepatic cholesterol but was associated with down-regulation of hepatic LDL receptors. Intravenous injection of [*4C]Lys into rabbits fed Lys + Met-enriched or Lys + Leu-enriched amino acid diets showed greater incorporation of label after 2-3 h into LDL apoprotein B in the more hypercholesterolemic animals fed Lys + Met diet (P < 0.05). Incorporation of the label into liver sterols and other lipids was similar on both diets, These results suggest that dietary hypercholesterolemic amino acids increase the level of LDL in serum by decreasing receptormediated uptake of LDL and by increased synthesis of apoprotein B. These effects are not associated with alteration in liver cholesterol metabolism. Low density lipoprotein entry and retention in the artery wall in vivo &.Qorthv RR, Thubrikar MJ, Robicsek R, Heineman Med. Res.
11191
Lab., Carolinas Med. Center, 1000 Blythe Blvd., Charlotte, NC 28203. USA
Aiherosclerosis X, Montrenl, October I994
compound heterozygous HL deficiency. However, the metabolic function of HL in lipoprotein metabolism is still not clear. We identified a patient with homozygous HL deficiency from 500 unrelated hypertriglyceridernic patients by measuring the HL immunomactive mass in postheparin plasma (PHP) using sandwith EIA (.J Lipid Res 1990; 31: 1911-1924) followed by analysis of HL gene abnormalities using PCR-SSCP and direct sequencing methods. The patient had a missense mutation in exon 3 of the HL gene, leading to no detectable mass in PHP. This was confirmed
211
by expressing the mutant HL in COS-1 cells. The patient’s serum was clear despite a TG of 320 mg/dl, characteristic of type N hyperlipoproteinemia. Analysis of fractionated lipoproteins showed an accumulation of IDL, TG-rich LDL and HDL, whereas VLDL was within the normal range. Absence of B-VLDL was confirmed by agarose electrophoresis. These results indicate that HL is primarily involved in the catabolism of TG in relatively small lipoproteins such as IDL, LDL and HDL.
LIPOPROTEINS pij
Hypocholesterolemia and malignancy Marsh S’, h&&&A’, Leviov M2 Mashiach T3, Wolfowitz El, Cohen E2, Robinson E2, Brook JG’, tDept. ofMed. ‘D’and Lipid Unif, ‘Dept. of Oncol. and 3Dept. of Quality Control, Technion, Faculty of Med., Haifa, Israel, 31096
The objective of this study was to determine the relationship between hypocholesterolemia and malignancy. TC and LDL-C values were compared to controls, and correlations made between patients with localized as opposed to disseminated disease. Patients referred for initial oncological treatment from October 1992 to February 1994 were randomly included. The control group comprised healthy individuals undergoing a routine check-up. This group was sex and age matched with respect to the patients. There were 266 patients (mean age 60f 14) comprising 110 men and 156 women. Controls comprised 262 subjects (mean age 56f 10) including 139 men and 123 women. The values of TC and LDL-C were 221+ 50 and 174 zk46 respectively, in the patient population, and these values did not differ from the controls. Among subjects with cancer, the levels of TC were lower in those with metastatic disease (202 f 50) than in those with localized disease (230 f 49) (P = 0.0001). Differences in LDL-C values were also significant (155 & 42 vs 177 -+42) (P = 0.015). Patients with metastatic disease had significantly lower values of cholesterol (P = 0.008) and LDL-C (P = 0.019) than controls. Furthermore, cholesterol levels below 175 mg/dl were found in 19/55 (35%) patients with extensive disease and only 39/263 (15%) of the control subjects (P = 0.003). In patients with cancer, cholesterol and LDL values were higher for women (229 f 53 and 182+51 respectively) than for men (21Ort43 and 164*36 respectively). Colon cancer and Iymphoma were associated with significantly lower levels of cholesterol than control patients. In conclusion, metastatic tumor is associated with significantly lower cholesterol levels, which could be secondary to overutilization of cholesterol by an increased population of cancer cells in patients with extensive disease. 11171
Influence of puberty, body composition and diet on IipopFteins n KM Willows N2, Grimston S, Hanley D2, ‘Dept. of
Pediatrics, Unk. of Manitoba, Winnipeg, MB. Canada, R3E 022; ‘Dept. of Med., Univ. of Calgary
To examine the influences of sexual maturation, body composition, and diet on serum lipoproteins, 109 healthy adolescents (58 female, 51 male) participating in competitive athletics were subdivided into 3 groups according to Tanner pubertal stage (Tl, T2/3, T4/5). A 6-day diet history, body composition and fasting lipoproteins, apolipoproteins and sex steroids were measured. As puberty progressed, lower TC (P = 0.001). apolipoproteins (P = 0.02) and LDL-C (P = O.OOl),and higher TG (P = 0.03) were seen in both sexes. Lower apolipoprotein A (P = 0.001) and HDLC (P = 0.001) were seen in males only. In late puberty, males had lower levels of apo A and HDL-C (P = 0.001) than females. Fat consumption as a percentage of calories (P = 0.02) decreased with
pubertal progression in both sexes. Females in all pubertal groups demonstrated increased adiposity compared to males in that their sum of 10 skinfolds and the amount of fat/muscle (FAT/MUS) were greater. In males, multiple regression analysis showed that advancing pubertal stage is a significant predictor of apo A (r = -0.60), TC (r = -0.53) and LDL-C (r = -0.40). Estradiol was a predictor of the TCHDL ratio (r = +0.34) and TG (r = +0.57). In females, serum testosterone was a significant predictor of apo B (r = -0.26) and TCXIDL (r = -0.40). FAT/MUS predicted TG (r = +0.29) and HDL-C (r = 4.35) and the waist/hip ratio, apo B (r = +0.36) and HDL-C (r=+O.29). The percentage of non-dairy fat consumed predicted apo B (r = -0.27) and percentage of dairy fat, HDL-C (r = 4.34). No variables correlated with apolipoprotein(a) levels in males or females. In sununary, sexual maturation and increased endogenous estrogen levels have significant impact on lipoproteins in adolescent males. Body composition and diet are more important predictive variables among adolescent females. Investigation of cholesterolemic responses to dietary amino acids and the mechanisms involved Kurowska EM, Carroll KK, Dept. of Biochem., Centre for Human
11181
Nutrition, Univ. of Western Ontario, London, ON, Canada N6A XI
Casein and other animal proteins are known to be more hypercholesterolemic than soy protein and other plant proteins when fed to rabbits in low-fat, cholesterol-free, semipurified diets. Studies in which a casein amino acid mixture or modifications of that mixture were fed to rabbits in the same type of diet indicated that the above differences are related to the higher content of some essential amino acids (especially Lys and Met) and the lower content of Arg and non-essential amino acids in casein than in plant proteins. The hypercholesterolemia produced by high levels of casein amino acids was not accompanied by changes in hepatic cholesterol but was associated with down-regulation of hepatic LDL receptors. Intravenous injection of [*4C]Lys into rabbits fed Lys + Met-enriched or Lys + Leu-enriched amino acid diets showed greater incorporation of label after 2-3 h into LDL apoprotein B in the more hypercholesterolemic animals fed Lys + Met diet (P < 0.05). Incorporation of the label into liver sterols and other lipids was similar on both diets, These results suggest that dietary hypercholesterolemic amino acids increase the level of LDL in serum by decreasing receptormediated uptake of LDL and by increased synthesis of apoprotein B. These effects are not associated with alteration in liver cholesterol metabolism. Low density lipoprotein entry and retention in the artery wall in vivo &.Qorthv RR, Thubrikar MJ, Robicsek R, Heineman Med. Res.
11191
Lab., Carolinas Med. Center, 1000 Blythe Blvd., Charlotte, NC 28203. USA
Aiherosclerosis X, Montrenl, October I994