Divergent responses of the liver to increased delivery of glucose or fatty acids: implications for the pathogenesis of type IV hyperlipoproteinemia.

This study examines the patterns of response of primary cultures of hamster hepatocytes to increased delivery of glucose or oleate. Increased glucose in the medium produced: (1) increased triglyceride in the cells and the medium; (2) no change in cholesterol ester in the cells or the medium; (3) no change in apo B100 secreted into the medium; (4) more apo B100 particles within the VLDL range with an increase in the VLDL triglyceride to apo B100 ratio. By contrast, increased oleate in the medium resulted in: (1) increased triglyceride in the cells and the medium; (2) increased cholesterol ester in the cells and the medium; and (3) increased apo B100 secreted into the medium. Important differences in the intracellular metabolism of triglyceride and cholesterol ester were also documented. Under all circumstances, there was substantially more radiolabelled triglyceride (overall eight times more) in the cell than in the medium, indicating that up to 90% of the newly synthesized triglyceride enters the cellular pool rather than being secreted with apo B100. By contrast, almost half of the newly synthesized cholesterol ester molecules were secreted with apo B100, pointing to an equal probability of entering the cell storage pool as opposed to being secreted. The data establish therefore two patterns of response of the liver to increased triglyceride synthesis depending on whether the substrate drive is glucose or oleate.

Hypertriglyceridemia associated with Trypanosoma brucei brucei infection in rabbits: role of defective triglyceride removal.

Rabbits infected with Trypanosoma brucei brucei develop a hypertriglyceridemia characterized by an increase in very low density lipoprotein and, to a lesser extent, low density lipoprotein, with a decrease in high density lipoprotein. Triglyceride production studies showed that the triglyceride production rate was not significantly different in trypanosome-infected rabbits from controls. Studies of triglyceride degradation using very low density lipoprotein triglyceride endogenously labelled with [3H]palmitate demonstrated a marked slowing of triglyceride removal in the infected rabbits when compared to controls. Lipase activity in post-heparin plasma was found to be deficient in trypanosome-infected animals. Furthermore, the greater the decrease in lipolytic activity, the greater the increase in serum triglyceride level. We conclude that the hypertriglyceridemia associated with T. b. brucei infection in rabbits results predominantly from a defect in triglyceride degradation.

Serum lipids, "double pre-beta lipoproteinemia," and distribution of the apo-very-low density (VLDL) lipoprotein peptides in hypothyroid patients before and after substitution therapy.

Thirty-six hypothyroid patients had total thyroidectomy for cancer. Thirty of them were studied before and during hormone replacement therapy, 1-1 .1 microgram/kg triiodothyronine (T3) per day. Mean treatment period was 90 days. During treatment mean serum total cholesterol (TC), triglycerides (TG), the ratio of TC to TG in very-low-density lipoprotein and the prevalence of the "double pre-beta VLDL lipoproteinemia" (Double-PBL) were significantly reduced as compared to the pretreatment values. The VLDL peptides were separated bysoelectric focusing (IEF) in polyacrylamide gel. The relative content of apolipoprotein E (arginine-rich apoprotein) and the E/C-peptides ratio were significantly reduced after T3 therapy. On the contrary, the content of C11 peptide was significantly increased. Apoprotein E was positively correlated with serum TC. The proportion of the intermediate density lipoprotein fraction, evaluated by agarose gel electrophoresis, consistently decreased after treatment. The results of our study suggest that thyroid hormones affect the metabolism of remnant lipoproteins.

Evaluation of the intravenous fat tolerance test in chronic renal disease.

The intravenous fat tolerance test (IVFTT) was performed on 17 controls, 25 patients with non dialyzed, non nephrotic chronic renal failure and 32 patients on hemodialysis. The fractional removal rate of triglyceride (K2) from plasma is decreased to the same degree in renal disease whether treated by hemodialysis or not. There was an inverse relationship between K2 and both serum triglyceride and fasting blood sugar, which were significantly increased compared to controls. The IVFTT also separated patients with renal disease and hypertriglyceridemia into two groups. One, where there was a low K2, suggesting that defective clearance of triglyceride was the major etiological factor in the hypertriglyceridemia and two, those patients with a normal K2 value, where other factors appear to be more important.

Cardiovascular risk factors and age of onset of obesity in severely obese patients.

Aim of this study was to evaluate whether the age of onset of obesity might affect the prevalence of CV risk factors in severely obese patients. Five hundred forty-five (385 F aged 42.3 +/- 7.1 yrs, BMI 47.3 +/- 5.1 w/h2 and 160 M of 39.0 +/- 1.1 yrs and BMI of 41.8 +/- 5.3 w/h2) severely obese patients hospitalized in the Metabolic Unit between 1972 and 1985 were subdivided in four classes according to the age of onset of obesity. Severely obese women with maturity onset obesity (i.e. onset greater than or equal to 20 yrs) (MOO) had higher (p less than or equal to .01) serum glucose (118 vs 103 mg/dl) and triglyceride (167 vs 126 mg/dl) than those with early onset obesity (EOO) (i.e. onset less than or equal to 3 yrs) with the same age, BMI and smoking habits. Similar trend was also found in men. In males arterial blood pressure was found to be higher (p less than or equal to .01) in EOO than in MOO (SBP = 152 vs 133 mmHg and DBP = 92 vs 83 mmHg). Similar trend was found in females. In conclusion age of onset of obesity may, at least in part, affect the prevalence of cardiovascular risk factors in severe obesity.

[Role of blood insulin in the etiology of dyslipoproteinemias and ischemic heart disease in males aged 20-69 years]. / Znachenie urovnia insulinemii v rasprostranennosti dislipoproteidemii i ishemicheskoi bolezni serdtsa u muzhchin 20-69 let.

A random sample of males aged 20-69 years and living in one of the administrative districts of Moscow was studied. The total number of those enrolled was 1225, and they were studied for the incidence of dyslipoproteinemias and coronary heart disease (CHD) in relation to the level of glycemia, basal insulinemia, diabetes mellitus or impaired tolerance to glucose. It was shown that the effect of disorders of carbohydrate metabolism is largely determined by the level of insulinemia and is mediated through the development of dyslipoproteinemias. The prevalence of CHD without dyslipoproteinemias as well as in combination with arterial hypertension or an excessive body weight did not depend on the level of glycemia and baseline insulinemia or the presence of diabetes mellitus. Hyperinsulinemia was found to be associated with types of dyslipoproteinemias most unfavourable in terms of CHD development.

[Role of excessive body weight and hormonal changes in the development of the main types of hyperlipoproteinemia]. / RoL' izbytochnoi masy tela i gormonal'nykh sdvigov v razvitii osnovnykh tipov giperlipoproteidemii.

Hyperlipoproteinemia (HLP) was detected in 67.3% of 118 males without CHD (with the mean age of 44.7 years) engaged in intellectual occupations. The excessive body weight in this group was twice higher, and blood insulin 1.5 times higher, while the STH levels twice lower as compared to patients with normolipoproteinemia (NLP). The mean concentrations of ACTH, cortisol, T3, T4 in both groups were equal and did not exceed normal. In males with the II A type of HLP versus those with the II B and IV types, the excessive body weight and blood cortisol content were 1.5 times as low but testosterone levels were 1.5 times as high and approached those in individuals with NLP.

Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia.

Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explain the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia.