Tuesday June 27, 2000: Poster Abstracts P:W7 Fatty Acids: The Link Between Insulin Resistance'and Dyslipidaemia
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lipoprotein particles in hepatic microsomes revealed significant differences in the pattern and density of lipoproteins. Immunoblot analysis of the intraceUular mass of microsomal Iriglyceride transfer protein (MTP), a key enzyme involved in VLDL assembly, showed a striking 2.1 fold elevation in hepatocytes derived from fructose-fed vs. control hamsters. MTP mRNA levels were also significantly increased in fructose-fed hamster livers. Direct incubation of hamster hepatocytes with various concentrations of fructose did not direcdy stimulate apoB intracellular stability of extracellular secretion. Conclusion: Hepatic VLDL-apoB overproduction in fructose-fed hamsters appears to result from increased intracellular stability of nascent apoB and an enhanced expression of MTP, which act to facilitate the assembly and secretion of apoB-containing lipoprotein particles. TuP24:W7 J The Sstl polymorphism at the apolipoprotein C-Ill gene locus predict insulin sensitivity in healthy subjects Francisco P6rez-Jim~nez, Jos~ L6pez-Miranda, Maria Jos6 Velasco, Dolores PiniUos, Pedro Castro, Pablo P6rez Martinez, Purificaci6n G6mez, Carmen Matin, Dolores Bravo, Jose M. Ordovas, Jean Mayer. Hosp Reina
Sofia, C6rdoba, Hospital Alto Guadalquivir, Andujar, Spain; Tufts Univ. Boston, MA, USA The expression of insulin resistance, a condition related with type 2 diabetes mellitas, results from the interaction of environmental and genetic factors. We have examined the influence of apo C-III Sst-I polymorphism on insulin sensitivity in 59 healthy young population (30 males and 29 females). Methods: They were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a high SAT diet (38% of energy as fat, 20% SAT). The second and third dietary periods were administered following a randomized crossover design, and consisted of an NCEP step I diet (28% fat, <10% SAT) and high MUFA diet, (Mediterranean diet, with 38% fat, 22% MUFA). All food and drinks were prepared and provided in the research kitchen. We determined the in vivo insulin resistance using the insulin suppression test with somastostafin. Results: Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significandy lower in S1 male, compared with $2 male, after SAT diet (100 4- 10 vs 161 4- 23), NCEP-I diet (90 4- 11 vs 110 -411) and Mediterranean diet (86 4- 10 vs 130 -4- 13). The apt C-HI gene effect was independent of the Xba-I polymorphism of the glycogen sintase gene. Condnsious: In summary, our results show an improvement in insulin sensitivity in males with the S 1 allele of the apt O i l polymorphism, independent of the improving effect observed with the substitution of MUFA and carbohydrates for SAT fat.
1 TuP25:W7 ] Impact of body mass index on the expression of hypertriglyceridemia in familial lipoprotein Upase (LPL) deficiency is related to the type of LPL gene mutation P. Julien 1, J. Bergeron I , D. Gaudet 2, IF. Cadelis I , P. Perron 2. ;Lipid Research
Ctr, Ste-Foy; 2Lipid Clinic, Chicoutimi, Quebec, Canada Objective: To assess the consequences of beterozygosity for LPL gene variants on the expression of hypertriglyceridemia (hyperTg) in individuals with normal to elevated body mass index (BMI). Method: Subjects, not taking drugs, were divided into quartiles based on BMI. Within each group, beterozygote carriers of LPL alleles leading to total (P207L or G188E) or partial (D9N) LPL deficiency were compared. All groups were paired for sex, apoE2 and age. Results: Analyses revealed similar concentrations of plasma Tg in individuals with partial or total LPL deficiency and low BMI (<24). However, significantly higher and increasing levels of plasma Tg have been found in carriers of P207L or G188E mutations with BMI 24-27, 27-31 or 31, Thus, at BMI > 31, carriers of P207L or G188E mutations had plasma Tg 2.7-fold higher than carriers of D9N. Based on VLDL Tg, LDL and HDL cholesterol, it is of interest to note that deterioration of the lipoprotein profiles was more pronounced in subjects carrying the P207L or G18E gene mutation, as well as in males compared to females. VLDL Tg levels in heterozygotes carrying an allele with partial or total LPL deficiency by BMI quartile BMI N (Part,/Def) Partial deficiency Total deficiency A (total VS partial) (Mean :t= SEM. *p < 0.05)
<24
24-27
27-31
>31
20/13 1,7 4- 0.3 2,1 4- 0.5 0,4
35/26 2.1 4- 0.3 3.1 4- 0.3 1.0"
30/24 3.1 4- 0.5 4.3 4- 0.6 1.2"
22/29 3,2 4- 0.4 5.2 4- 1.0 2.0*
Conclnsions: These findings indicate that the effect of increased BMI on dyslipoproteinemia is most apparent in male heterozygotes carrying an LPL allele expressing total LPL deficiency. Furthermore, this gene-environment interaction suggests an increased risk of CAD. TuP26:W7 [ The e f ~ t of combined therapy of atenolol with simvastatin and with fenoflbrat on the insulin resistance syndrome M.N. Mamedox(, O.V. Kosmatova, N.V. Perova, R.G. Oganov. National
Research Center for Preventive Medicine, Moscow, Russia It is known that nonselective beta blockers aggravate the abnormalities of carbohydrate and lipid metabolism. On the other hand, the sympatho-adrenergic system play a larger role in the pathogenesis of metabolic syndrome. Aim of Study: to investigate the effect of a combined therapy of selective beta-blockers with statins and fibrates on the metabolic alterations of insulin resistance syndrome. Materials and Methods: 37 men and women aged 40--59 (55 + 2) with metabolic syndrome were randomized into 2 groups: I group of patients (n --- 18) received simvastatin 10 mg (MSD, USA) with atenolol 50 mg daily (Norton, UK), II group (n = 19) fenofibrat 200 ME (Fouruier, France) in combination with atenolo150 mg daily for a period of 8 weeks. The criteria for metabolic syndrome components were the following: AH-SBP 140-169 mm Hg and/or DBP 90--99 mm Hg; Abdominal obesity (AO)-waist to hip ratio > 1.0 for men and >0.85 for woman if BMI > 25 kg/m2; Hyperlipidemia (HLP)- Tg level 200 mg/dl and/or total Ch 250 mg/dl; Glucose intolerance basal plasma glucose level up to 120 mg/dl and 2 hours after 75 g glucose load, 140-200 mg/dl. Results: On treatment during 8 weeks SBP and DBP levels in patients of I group decreased by 18% and 16% (p < 0.001 and p < 0.01), in patients of II group by 14% and 13.8% (p < 0.01). Tg (20%, p < 0.05) and total Ch levels (29%, p < 0.001) in I group, 43% (p < 0.001) and 18.8%, (p < 0.01) in II group statistically decreased. HDL Ch (16%, p < 0.05) increased only in I group. Like the basal levels, post prandial levels of glucose and immunoreactive insulin in both groups had tendency to decrease. At the same time in the II group post prandial insulin level decreased significantly by 7% (p < 0.05). Conclusion: Both the combinations improves blood pressure and lipid profile changes involved in insulin resistance syndrome and have a neutral effect on carbohydrate metabolism. However the combination of fenofibmt with atenolol significantly decreases post prandial tissue insulin resistance. Selective beta blockers in mean doses combined with hypolipidemic drugs (statins and fibrates) can be administered to correct metabolic syndrome. TuP27:W7 ] Effect of troglitazone on plasma lipid metabolism and
lipoprotein lipase M. Hikita, J. Kobayasbi, H. Bujo, K. Takahashi, M. Otabe, N. Morisaki, Y. Saito. Second Department of Internal Medicine Chiba University School of
Medicine, Chiba, Japan Objective: To clarify how troglitazone, an insulin-sensitizing agent, affects lipid metabolism and post-heparin plasma lipoprotein lipase (LPL). Methods: Fifteen patients (3 male, 12 female) [the average age 62 + 7 y; the mean body mass index, 25 4- 3 kg/m 2] were recruited and the serum lipids and post-heparin plasma lipoprotein lipase (LPL) mass before and 4 weeks after oral administration of troglitazone (200 mg per day) were measured. Mouse preadipocyte cell line, 3T3-LI cells were treated with this compound and LPL enzyme protein mass in the culture media was measured by an enzyme linked immunosorbent assay. A reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis was conducted to investigate the effect of this compound on the expression of LPL. Results: The average levels before treatment of fasting serum total cholesterol, triglycerides and high density lipoprotein-cholesterol, plasma glucose and glycohemoglobin Ale were 216 4- 34, 160 4- 84, 57 4- 19, 145 5= 30 mg/dl and 7.8 4- 1.6%. Four weeks after treatment, those levels were 209 436, 105 4- 27 (p = 0.004), 63 4- 19 (p = 0.02), 139 -I- 41 mg/dl and 7.3 4- 0.6% (p = 0.01), respectively. The postheparin plasma LPL mass increased from 226 4- 39 to 257 4- 68 ng/ml (p = 0.03) during that period. RT-PCR and Northern blot analysis revealed that in the cultured 3T3-L 1 cells, the expression of LPL was enhanced in the presence of troglitazone. Conclusions: These results suggest that troglitazone improves plasma triglyceride-rich lipoproteins metabolism by enhancing the expression of LPL in adipocytes.
Xllth International Symposium on Atherosclerosis, Stockholm, Sweden, June 25-29, 2000