High-cholesterol Diets Induce Changes in Lipid Composition of Rat Erythrocyte Membrane Including Decrease in Cholesterol,Increase in α-Tocopherol and Changes in Fatty Acids of Phospholipids

Effects of high dietary cholesterol on erythrocyte membrane lipids were studied. Feeding rats with a diet containing 0.5% cholesterol and 0.15% sodium cholate for two weeks induced changes in erythrocyte membrane lipids including a decrease in cholesterol, an increase in α-tocopherol (α-Toc) and changes in the fatty acid composition of phospholipids. Oleic acid and linoleic acid increased, while arachidonic acid decreased in phosphatidylcholine. Saturated fatty acids decreased and unsaturated fatty acids increased in phosphatidylethanolamine. Almost the same changes in membrane lipids were also noted after six weeks of feeding rats with the diet. A diet containing 0.5% cholesterol but without sodium cholate caused a decrease in erythrocyte cholesterol and an increase in erythrocyte α-Toc after two weeks of feeding, as compared to the basal diet, indicating that high dietary cholesterol, but not sodium cholate, was responsible for these changes in the erythrocyte membrane.     

Association of Adenovirus Infection with Human Obesity

DHURANDHAR, NIKHIL V, PUSHPA R KULKARNI, SHARAD M AJINKYA, ABHAYA A SHERIKAR, RICHARD L ATKINSON. Association of adenovirus infection with human obesity. We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p<0.02) and body mass index (p<0.001) (95.1 ± 2.1 kg and 35.3 ± 1.5 kg/m², respectively) compared with the N-AGPT group (80.1 ± 0.6 kg and 30.7 ± 0.6 kg/m², respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p<0.02) and triglyceride (p<0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.     

Circadian Assessment of Lipids in the Hyperphagic Obese Rat Compared with Lean Litter-Mates

Time and feeding influences on cholesterol, triglyceride, glucose and insulin levels, and serum cholinesterase activity were assessed in a genetically-hyperlipidemic hyperphagic obese rat model, and compared with its lean litter-mate. Following a 28-day acclimation to a 12-hr light/dark cycle, blood samples were obtained every 2 hr from rats via tail bleed for a 24-hr period. Synchronization with other animal studies was established by endogenous serum Cortisol levels [acrophase 18-20 hr after light onset (HALO) in both groups]. Triglycerides cholesterol, insulin and glucose levels were significantly elevated in obese versus lean rats. Obese rats were observed to feed throughout the 24-hr cycle, whereas lean litter-mates ate only during the dark cycle. No circadian rhythmicity was found in glucose levels with either rat group. Insulin levels were not correlated. Although triglyceride levels peaks at 13 HALO in lean rats, no pattern was observed in obese rats. Cholesterol levels were unchanged with time in either group. Cholinesterase activity followed a circadian rhythm in the lean, but not obese, rats with an acrophase estimated at 8 HALO. In contrast to previous reports, enzyme activity was not correlated with triglyceride levels in either rat group. Circadian similarities in insulin levels between rat groups suggest changes in insulin metabolism and/or secretion which are likely to be independent of feeding or activity. Conversely, triglyceride levels remained elevated throughout the 24-hr period in obese rats, whereas significant increases were observed in lean rats during the dark active cycle. These data suggest that triglyceride levels, and not insulin and cholesterol levels, are most likely dependent on feeding patterns.     

Retention of human skin fibroblast fatty acid modifications during maintenance culture

Summary The fatty acid composition of cultured human skin fibroblasts was modified by adding either oleic or linoleic acid to the growth medium. After the cultures became confluent, they were washed and transferred to different maintenance media in order to determine the stability of the various fatty acyl modifications. Some changes in fatty acid composition occurred under all conditions. When the maintenance medium was supplemented with fatty acid, the cellular neutral lipid and phospholipid fatty acyl composition were altered markedly within 16 to 24 hr. If no supplemental fatty acid was available during the maintenance period, however, the modified fatty acyl compositions were sufficiently retained so that appreciable differences between the cells enriched with oleate and linoleate persisted for at least 48 to 72 hr. This considerable degree of stability occurred when either 10% delipidized fetal bovine serum or 10% fetal bovine serum containing its inherent lipids were present in the maintenance medium. Although the triglyceride content of the fatty acid-modified cells was quite labile, neither the cholesterol nor phospholipid content changed appreciably during culture in any of the maintenance media. Since the fatty acid compositional differences persisted during several days of maintenance under certain conditions, these modified cultures appear to be a useful experimental system for assessing the effect of lipid structure on fairly long-term cellular functions. This work was supported by Arteriosclerosis Specialized Center of Research Grant HL14230 from the National Heart, Lung and Blood Institute, National Institutes of Health.