Regression analysis of the combined published data on the effects of dietary fatty acids and cholesterol on serum cholesterol and lipoprotein cholesterol evaluated with groups of human subjects shows that 1) saturated fatty acids increase and are the primary determinants of serum cholesterol, 2) polyunsaturated fatty acids actively lower serum cholesterol, 3) monounsaturated fatty acids have no independent effect on serum cholesterol and, 4) dietary cholesterol increases serum cholesterol and must be considered when the effects of fatty acids are evaluated. More limited data on low-density-lipoprotein cholesterol (LDL-C) show that changes in LDL-C roughly parallel the changes in serum cholesterol but that changes in high-density-lipoprotein cholesterol cannot be satisfactorily predicted from available data.
The lipodystrophy syndrome (adipose tissue redistribution and metabolic abnormalities) observed with highly active antiretroviral therapy (HAART) during human immunodeficiency virus (HIV) infection may be related to increased proinflammatory cytokine activity. We measured acute cytokine (TNF-α, IL-6, leptin), glycerol, and lactate secretion from abdominal subcutaneous adipose tissue (SAT), and systemic cytokine levels, in HIV-infected subjects with and without lipodystrophy (HIVL+ and HIVL–, respectively) and healthy non-HIV controls. Lipodystrophy was confirmed and characterized as adipose tissue redistribution in HIVL+ compared with HIVL– and controls, by dual-energy X-ray absorptiometry and by whole body MRI. TNF-α secretion from abdominal SAT and circulating levels of IL-6, soluble TNF receptors I and II, and insulin were elevated in HIVL+ relative to HIVL– and/or controls, particularly in HIVL+ undergoing HAART. In the HIV-infected group as a whole, IL-6 secretion from abdominal SAT and serum IL-6 were positively associated with visceral fat and were negatively associated with the relative amount of lower limb adipose tissue ( P < 0.01). Decreased leptin and increased lactate secretion from abdominal SAT were specifically associated with HAART. In conclusion, increased cytokine secretion from adipose tissue and increased systemic proinflammatory cytokine activity may play a significant role in the adipose tissue remodeling and/or the metabolic abnormalities associated with the HIV-lipodystrophy syndrome in patients undergoing HAART.
Our previous finding that a waist-to-hip ratio (WHR) >0.85 was not associated with similar health risks in black, compared with white, obese premenopausal non-diabetic women of similar fatness is attributed to either 1) a different relationship between WHR and visceral adiposity or 2) differences in the relationship between visceral adiposity and the metabolic abnormalities of obesity. We measured visceral (VAT) and subcutaneous adipose tissue (SCAT) areas at midwaist in 25 black and 25 white obese nondiabetic pre-menopausal women with similar BMI, percentage body fat, and wide range of WHR (0.7-0.95 for black women and 0.7-0.9 for white women) and then compared insulin sensitivity index (SI), glucose and insulin areas under the 2-h curve (AUCs) during an oral glucose tolerance test (OGTT), and blood lipids in the two groups before and after adjustments for total body and visceral adiposity. After adjusting for total body fat mass (FM), obese black women had significantly less VAT (by 32 cm2) and lower VAT/SCAT for any given WHR. The regression equations predicting the SI the glucose and insulin AUCs, and the triglyceride and HDL cholesterol levels from regional adipose tissue measurements (VAT, SCAT, or VAT/SCAT) and from total body fat (FM or percentage body fat) had slopes that were not significantly different for black and white women. LDL cholesterol levels were independently related to VAT in black but not in white women. The black women had a similar SI insulin AUC, and triglyceride levels but significantly lower glucose AUC and higher HDL cholesterol levels (P < 0.001), after adjusting for VAT and FM. Regression analysis of the pooled data showed that high VAT and high VAT/SCAT, but not SCAT, predicted lower SI higher glucose and insulin AUCs during OGTT, and higher triglyceride levels, independent of total adiposity. We conclude that while increases in VAT and VAT/SCAT adversely affect metabolism in both black and white obese premenopausal women, similar levels of total body and visceral adiposity are associated with different metabolic risk factors in these groups.
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