Effects of obesity and body fat distribution on lipids and lipoproteins in nondiabetic American Indians: The Strong Heart Study. Obes Res. 2000;8:411-421. Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/ lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m 2 ) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m 2 ), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r ϭ Ϫ0.24, p Ͻ 0.001). There was a significant but weak relation with apoAI (r ϭ Ϫ0.14, p Ͻ 0.001). Waist circumference was positively related to triglycerides (r ϭ 0.14, p Ͻ 0.001) and negatively related to HDL cholesterol (r ϭ Ϫ0.23, p Ͻ 0.001) and apoAI (r ϭ Ϫ0.13, p Ͻ 0.001). In men, BMI was positively correlated with triglycerides (r ϭ 0.30, p Ͻ 0.001) and negatively correlated with HDL cholesterol (r ϭ Ϫ0.35, p Ͻ 0.001) and apoAI (r ϭ Ϫ0.23, p Ͻ 0.001). Triglycerides increased with waist circumference (r ϭ 0.30, p Ͻ 0.001) and HDL cholesterol decreased with waist circumference (r ϭ Ϫ0.36, p Ͻ 0.001). In both women and men there was an inverted U-shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (Ϫ1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (Ϫ0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles ...

Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol.

Abnormalities in plasma lipoprotein concentrations commonly found in subjects with noninsulin-dependent diabetes may be related to insulin resistance, hyperinsulinemia, hyperglycemia, or other metabolic defects. The middle-aged obese rhesus monkey is an animal model in which these defects can be separated in time during the development of diabetes. It is, therefore, a model system for examining the sequence of metabolic changes which occur before and after the onset of diabetes. This sequence of changes was used in the present study to determine if lipoprotein changes occur in association with the development of diabetes in the rhesus monkey. Increases in plasma triglyceride, very low density lipoprotein (VLDL) triglyceride, and VLDL cholesterol, and decreases in high density lipoprotein cholesterol were observed across previously identified groups ranging from normal to diabetic. Plasma triglycerides increased from 0.54 +/- 0.09 (normal) to 1.27 +/- 0.50, 1.93 +/- 0.79, and 4.28 +/- 2.24 in three intermediate groups with progressive hyperinsulinemia and insulin resistance, to 7.59 +/- 2.73 mmol/L in the diabetic monkeys. Increases in VLDL triglyceride and VLDL cholesterol paralleled the plasma triglyceride increases. High density lipoprotein cholesterol decreased across the groups from 2.33 +/- 0.16 (normal) to 1.72 +/- 0.20, 1.17 +/- 0.13, and 1.09 +/- 0.20 mmol/L in the intermediate groups, and was lowest in the diabetic monkeys, 1.00 +/- 0.21. The obese rhesus monkey can therefore be used to study lipoprotein abnormalities as they occur both before and in noninsulin-dependent diabetes.

Mechanisms explaining the decrease in circulatory cholesterol levels after weight loss remain ill defined. The objective was to examine effects of weight loss as achieved through energy restriction upon human in vivo cholesterol biosynthesis. Six subjects (64-77 y, body mass index, 30.3 +/- 3.8 kg/m(2)) were recruited into a two-phase prospective clinical trial. In the first phase, subjects complied with American Heart Association (AHA) Step I diets for 3 mo with no change in their usual energy intake. After this weight-stable phase, subjects consumed an AHA Step I diet with a targeted reduction in energy intake of approximately 1000 kJ/d for 6 mo to achieve negative energy balance leading to weight loss. The incorporation rate of deuterium from body water into erythrocyte membrane free cholesterol over 24 h was utilized as an index of cholesterogenesis at the end of both phases. Subjects' mean weights decreased (P < 0.05) from 89.3 +/- 12.5 kg to 83.2 +/- 11.5 kg (6.8 +/- 2.6% of initial body weight) across phases. Circulating concentrations of total and LDL-cholesterol, and triglycerides also decreased (P < 0. 05) across phases. HDL-cholesterol concentrations were unchanged (P > 0.05). Cholesterol fractional synthetic rate (FSR) after phase 2 (3.04 +/- 1.90%/d) was lower (P < 0.05) than that after phase 1 (8. 42 +/- 3.90%/d). Absolute synthesis rate (ASR) after phase 2 [0.59 +/- 0.38 g/(kg. d)] also was lower (P < 0.05) than that after phase 1 [1.66 +/- 0.84 g/(kg. d)]. These data suggest that, in obese men, energy restriction resulting in even modest weight loss suppresses endogenous cholesterol synthesis, which contributes to a decline in circulating lipid concentrations.

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