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Biomedical subjects

R J Deckelbaum

Publications and source records attributed to R J Deckelbaum.

At least 19 recordsLinked to original sources
PubMed2001

Apolipoprotein E inhibits serum-stimulated cell proliferation and enhances serum-independent cell proliferation.

Independently of its role in lipid homeostasis, apolipoprotein E (apoE) inhibits cell proliferation. We compared the effects of apoE added to media (exogenous apoE) with the effects of stably expressed apoE (endogenous apoE) on cell proliferation. Exogenous and endogenous apoE increased population doubling times by 30-50% over a period of 14 days by prolonging the G(1) phase of the cell cycle. Exogenous and endogenous apoE also decreased serum-stimulated DNA synthesis by 30-50%. However, apoE did not cause cell cycle arrest; both apoE-treated and control cells achieved equivalent saturation densities at 14 days. Further analyses demonstrated that exogenous and endogenous apoE prevented activation of MAPK but not induction of c-fos expression in response to serum growth factors. Endogenous (but not exogenous) apoE altered serum concentration-dependent effects on proliferation. Whereas control (non-apoE-expressing) cell numbers increased with increasing serum concentrations (1.6-fold for every 2-fold increase in serum), apoE-expressing cell numbers did not differ as serum levels were raised from 2.5 to 10%. In addition, in low serum (0.1%), apoE-expressing cells had elevated DNA synthesis levels compared with control cells. We conclude that apoE does not simply inhibit cell proliferation; rather, the presence of apoE alters the response to and requirement for serum mitogens.

Animals↗
PubMed2001

Differential modulation of ACAT1 and ACAT2 transcription and activity by long chain free fatty acids in cultured cells.

Fatty acyl CoA and cholesterol are the substrates for cholesteryl ester synthesis by acyl coenzyme A:cholesterol acyltransferase (ACAT). Two ACAT genes have been identified; ACAT1 is expressed ubiquitously while ACAT2 is primarily expressed in intestine and liver. We tested effects of different free fatty acids (FFAs) on ACAT1 and ACAT2 expression and activity in HepG2 human hepatocytes and THP1 human macrophages. Incubation of oleic acid, arachidonic acid, or eicosapentaenoic acid, but not 25-hydroxycholesterol, induced ACAT1 mRNA levels 1.5--2-fold in HepG2, with no affect on ACAT2 mRNA. FFA had no affect on ACAT1 mRNA in THP1 cells. To determine if FFAs affect ACAT1 or ACAT2 posttranscriptionally, cells were labeled with [(3)H]cholesterol in the presence of the different FFAs for 1--5 h. Both HepG2 and THP1 cells showed the greatest cholesteryl ester production with oleic acid. This was also confirmed by the observation that more [(3)H]oleic acid incorporated into CE compared to [(3)H]eicosapentaenoic acid, even though there was no difference in the total uptake of these FFAs. In ACAT-deficient SRD4, CHO cells stably transfected with human ACAT1 or ACAT2, ACAT1 expressing cells showed a strong preference for oleic acid while ACAT2 expressing cells utilized unsaturated FFAs. Acyl CoA substrate specificity was further tested in microsomes isolated from these cells as well as HepG2 and THP1. THP1 and ACAT1 cells utilized oleoyl CoA preferentially. In contrast, HepG2 and ACAT2 microsomes utilized linolenoyl CoA as well. We conclude that FFAs increase ACAT1 mRNA levels in a cell specific manner, and furthermore that the ACAT reactions exhibit differential FFA utilization.

Animals↗
PubMed2001

AHA Science Advisory. Stanol/sterol ester-containing foods and blood cholesterol levels. A statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association.

Considerable attention in the recent past has focused on the potential benefits or adverse effects of butter versus different types of margarines, usually with respect to their relative content of polyunsaturated, saturated, and trans fatty acids, and the impact of these on low-density lipoprotein (LDL) cholesterol levels. Recently, a new class of margarines and other fat-derived products (eg, salad dressings, mayonnaise) containing plant-derived sterols that are intended for use to lower blood cholesterol levels have been introduced into the food supply. These products are being marketed as adjuncts to low-saturated-fat and low-cholesterol diets to maximize reductions in LDL cholesterol levels achievable by dietary means.

American Heart Association↗
PubMed2001

Cryptosporidium infection in Bedouin infants assessed by prospective evaluation of anticryptosporidial antibodies and stool examination.

An enzyme-linked immunosorbent assay system using oocyst lysate as antigen was used to detect serum- specific antibody responses to Cryptosporidium parvum between 1989 and 1994 in consecutive sera obtained at birth, and at the age of 6, 12, and 23 months, from 52 infants living in a Bedouin town located in the south of Israel. The serologic tests revealed high levels of immunoglobulin G anti-Cryptosporidium at birth that dropped significantly by the age of 6 months and then rose continuously to a geometric mean titer of 481 at age 23 months. The serum immunoglobulin M Cryptosporidium antibodies rose continuously from nearly undetectable levels at birth to a geometric mean titer of 471 (157-fold increase) at age 23 months. All the subjects already showed at 6 months a significant rise in immunoglobulin M. A significant rise in immunoglobulin A titers was detected in 48% and 91% of subjects at 6 and 23 months, respectively. By monthly surveillance, microscopy using the modified Ziehl-Neelsen method and confirmed by indirect immunofluorescence assay detected Cryptosporidium antigens in only 11% at age 6 months and 48% at age 23 months. The extent of exposure to Cryptosporidium immediately after birth as detected by serology is much higher than that predicted by frequent prospective assessment of stool samples.

Adult↗
PubMed2001

Overrestriction of dietary fat intake before formal nutritional counseling in children with hyperlipidemia.

OBJECTIVE: To assess the nutritional adequacy of the diets of children with hyperlipidemia following medically unsupervised low-fat diets compared with children receiving unrestricted diets. DESIGN: Case comparison study. PATIENTS AND OTHER PARTICIPANTS: Forty-six children were referred to the Children's Cardiovascular Health Center, Columbia-Presbyterian Medical Center, New York, NY, for treatment of hyperlipidemia who had achieved the Step I diet recommendations for total fat before formal nutritional counseling (mean age +/- SE, 9.7 +/- 0.3 years; sex distribution, 24 boys [53%]; ethnicity, 26 Latinos [57%] and 20 whites [43 %]; body mass index +/- SE, 22.4 +/- 0.7 kg/m(2)), and 34 healthy children participating in well-child visits at a local pediatric practice (mean age +/- SE, 10.2 +/- 0.4 years; sex distribution, 18 boys [54%]; ethnicity, 19 Latinos [57%] and 15 whites [43%]; body mass index +/- SE, 22.5 +/- 1.1 kg/m(2)). MAIN OUTCOME MEASURES: Three-day food records were analyzed by a registered dietitian using the Minnesota Nutrient Data System. Outcome measures were intakes of calories, total and saturated fats, carbohydrate, protein, essential fatty acids, fat-soluble vitamins, folate, vitamin C, calcium, iron, and zinc. RESULTS: The percentage of calories from fat and saturated fat was significantly lower in the hyperlipidemic population (mean +/- SE, hyperlipidemic vs control subjects: total fat, 22.7% +/- 0.7% vs 34.5% +/- 0.6%, P<.001; saturated fat, 7.9% +/- 0.3% vs 12.9% +/- 0.4%, P<.001). The caloric intake in controls was 17% higher than in patients with hyperlipidemia. Ninety percent of the decrease in calories in the hyperlipidemic group could be accounted for by the decrease in total fat intake. After adjusting for calories, no significant difference was noted between the groups for any of the vitamins and minerals mentioned earlier. CONCLUSION: Our findings suggest that before formal nutritional counseling, overzealous dietary fat restriction can occur in children with hypercholesterolemia.

Child↗
PubMed2001

Prevention and treatment of childhood obesity.

Obesity has reached epidemic proportions among children and youth in the United States. Surveys indicate that the number of overweight children aged 6 to 17 years has doubled within three decades. In the decade between the late 1970s and the late 1980s, the prevalence of overweight increased from 7.6% to 10.9% for children aged 6 to 11 years, and from 5.7% to 10.8% for adolescents aged 12 to 19 years. Data for 1999 indicates that the epidemic is continuing to increase, so that 13% of 6- to 11-year-old children and 14% of 12- to 19-year- old children are currently overweight (body mass index > or = 95th percentile for age/gender). This article reviews newer concepts related to etiologic factors, comorbidities, and strategies for prevention and treatment.

Adolescent↗
PubMed2001

HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia.

Highly active anti-retroviral therapies, which incorporate HIV protease inhibitors, resolve many AIDS-defining illnesses. However, patients receiving protease inhibitors develop a marked lipodystrophy and hyperlipidemia. Using cultured human and rat hepatoma cells and primary hepatocytes from transgenic mice, we demonstrate that protease inhibitor treatment inhibits proteasomal degradation of nascent apolipoprotein B, the principal protein component of triglyceride and cholesterol-rich plasma lipoproteins. Unexpectedly, protease inhibitors also inhibited the secretion of apolipoprotein B. This was associated with inhibition of cholesteryl-ester synthesis and microsomal triglyceride transfer-protein activity. However, in the presence of oleic acid, which stimulates neutral-lipid biosynthesis, protease-inhibitor treatment increased secretion of apolipoprotein B-lipoproteins above controls. These findings suggest a molecular basis for protease-inhibitor-associated hyperlipidemia, a serious adverse effect of an otherwise efficacious treatment for HIV infection.

Animals↗
PubMed2001

Childhood obesity: the health issue.

Overweight and obesity in children is epidemic in North America and internationally. Approximately 22 million children under 5 years of age are overweight across the world. In the United States, the number of overweight children and adolescents has doubled in the last two to three decades, and similar doubling rates are being observed worldwide, including in developing countries and regions where an increase in Westernization of behavioral and dietary lifestyles is evident. Comorbidities associated with obesity and overweight are similar in children as in the adult population. Elevated blood pressure, dyslipidemia, and a higher prevalence of factors associated with insulin resistance and type 2 diabetes appear as frequent comorbidities in the overweight and obese pediatric population. In some populations, type 2 diabetes is now the dominant form of diabetes in children and adolescents. Disturbingly, obesity in childhood, particularly in adolescence, is a key predictor for obesity in adulthood. Moreover, morbidity and mortality in the adult population is increased in individuals who were overweight in adolescence, even if they lose the extra weight during adulthood. Although the cause of obesity in children is similar to that of adults (i.e., more energy in vs. energy utilized), emerging data suggest associations between the influence of maternal and fetal factors during intrauterine growth and growth during the first year of life, on risk of later development of adult obesity and its comorbidities. In addition, recent data suggest that varying biological responses in different racial/ethnic groups differently contribute to overweight, obesity, and their comorbidities. Although differences in gene-nutrient interactions may contribute, the role of varying cultural and socioeconomic variables still needs to be determined to understand these disparities. Novel approaches in the prevention and treatment of childhood overweight and obesity are urgently required. With the strong evidence that a lifecycle perspective is important in obesity development and its consequences, consideration must be focused on prevention of obesity in women of child-bearing age, excessive weight gain during pregnancy, and the role of breast-feeding in reducing later obesity in children and adults. Consideration must be given to family behavior patterns, diet after weaning, and the use of new methods of information dissemination to help reduce the impact of childhood obesity worldwide.

Adolescent↗
PubMed2001

Oxidative stress is not enhanced in non-malnourished infants with persistent diarrhea.

Increased concentrations of reactive oxygen species (ROS) and depleted antioxidant defences have been implicated in a cycle of infection, malabsorption and malnutrition, leading to persistent diarrhea. In order to determine whether in non-malnourished children oxidative stress predisposes to the development of persistent diarrhea, infants with acute diarrhea (< 7 days) (n = 39) were compared to infants with persistent diarrhea (> 14 days) (n = 38). Lipid peroxidation was assessed by the TBARs assay and expressed as malondialdehyde equivalent content (nmol MDA/ml plasma), and levels of plasma antioxidants vitamin A and vitamin E were determined. In infants with acute and persistent diarrhea nutritional status, as assessed by weight/height and height-for-age, hemoglobin levels, serum albumin and immunoglobulin levels, did not differ between groups. Serum vitamin A and vitamin E levels did not differ in infants with acute or persistent diarrhea. TBARs, expressed as nmol MDA/ml plasma did not differ between infants with acute or persistent diarrhea and furthermore did not differ from levels in a healthy, similar age, control group. Non-malnourished infants with persistent diarrhea do not exhibit plasma antioxidant depletion or enhanced lipid peroxidation. In these infants, oxidative stress, as reflected in plasma, does not play a role in the pathogenesis of persistent diarrhea.

Analysis of Variance↗
PubMed2001

Hyperlipidemia and inhibitors of HIV protease.

HIV protease inhibitors have been successfully incorporated into therapy for patients with HIV. These otherwise efficacious treatments present with multiple metabolic side-effects and body habitus changes known as the lipodystrophy syndrome. Direct associations of the lipid abnormalities with protease inhibitor use have been described, and ongoing studies are focused on describing mechanisms for future intervention. Mechanisms based on the molecular identity of the protease inhibitor target with human proteins, interference with aspects critical to lipoprotein production, and interference with adipocyte differentiation have been described. This review highlights the complexities of this syndrome, and discusses putative mechanisms whereby protease inhibitors cause hyperlipidemia.

Adipocytes↗
PubMed2001

Calcium intake in preschool children--a study of dietary patterns in a low socioeconomic community.

BACKGROUND: There is a lack of published data on sources and quantity of calcium intake in preschool children. STUDY OBJECTIVES: To assess calcium intake compared with the Dietary Reference Intake (DRI), to identify major food sources of calcium, and to compare dietary patterns of healthy preschool children who do and do not meet the calcium DRI. DESIGN: Cross-sectional study. SETTING: Primary care pediatrics practice at a large urban medical center. SUBJECTS: A group of 228 children aged 44 to 60 months in a low socioeconomic community. METHODS: Diet was assessed using three or four 24-hour recalls administered approximately three months apart to the parents. Nutrient values were computed using a dietary analysis program based on USDA values. RESULTS: Mean daily calcium intake was 852 mg/day (S.D., 271) and 44% reported mean calcium intake less than the DRI of 800 mg/day. Milk consumption accounted for 64.3% and cheese for 6.7% of the daily calcium intake. Multiple linear regression analysis adjusting for age, sex, race, body mass index, and total caloric intake confirmed the main contribution of mainly milk and, to a much lesser extent, cheese consumption, as determinants of calcium intake. All of the children who consumed less than 1.2 servings of milk (288 ml) milk per day reported mean daily calcium intake below the DRI. CONCLUSIONS: Calcium intake below the DRI may be common in preschool children in low socioeconomic communities, and is associated primarily with lower milk intake. These findings indicate the need to promote the consumption of low-fat milk in preschool children.

Bone Density↗
PubMed2000

Lipoprotein lipase-mediated selective uptake from low density lipoprotein requires cell surface proteoglycans and is independent of scavenger receptor class B type 1.

Lipoprotein lipase (LpL) hydrolyzes chylomicron and very low density lipoprotein triglycerides to provide fatty acids to tissues. Aside from its lipolytic activity, LpL promotes lipoprotein uptake by increasing the association of these particles with cell surfaces allowing for the internalization by receptors and proteoglycans. Recent studies also indicate that LpL stimulates selective uptake of lipids from high density lipoprotein (HDL) and very low density lipoprotein. To study whether LpL can mediate selective uptake of lipids from low density lipoprotein (LDL), LpL was incubated with LDL receptor negative fibroblasts, and the uptake of LDL protein, labeled with (125)I, and cholesteryl esters traced with [(3)H]cholesteryl oleoyl ether, was compared. LpL mediated greater uptake of [(3)H]cholesteryl oleoyl ether than (125)I-LDL protein, a result that indicated selective lipid uptake. Lipid enrichment of cells was confirmed by measuring cellular cholesterol mass. LpL-mediated LDL selective uptake was not affected by the LpL inhibitor tetrahydrolipstatin but was nearly abolished by heparin, monoclonal anti-LpL antibodies, or chlorate treatment of cells and was not found using proteoglycan-deficient Chinese hamster ovary cells. Selective uptake from HDL, but not LDL, was 2-3-fold greater in scavenger receptor class B type I overexpressing cells (SR-BI cells) than compared control cells. LpL, however, induced similar increases in selective uptake from LDL and HDL in either control or SR-BI cells, indicative of the SR-BI-independent pathway. This was further supported by ability of LpL to promote selective uptake from LDL in human embryonal kidney 293 cells, cells that do not express SR-BI. In Chinese hamster ovary cell lines that overexpress LpL, we also found that selective uptake from LDL was induced by both endogenous and exogenous LpL. Transgenic mice that overexpress human LpL via a muscle creatine kinase promoter had more LDL selective uptake in muscle than did wild type mice. In summary LpL stimulates selective uptake of cholesteryl esters from LDL via pathways that are distinct from SR-BI. Moreover this process also occurs in vivo in tissues where abundant LpL is present.

Animals↗
PubMed2000

Endogenously expressed apolipoprotein E has different effects on cell lipid metabolism as compared to exogenous apolipoprotein E carried on triglyceride-rich particles.

Apolipoprotein E (apoE) on model triglyceride-rich particles (TGRP) increases triglyceride (TG) utilization and cholesteryl ester (CE) hydrolysis, independent of its effect on enhancing particle uptake. We questioned whether, under physiological concentrations, endogenously expressed apoE has similar effects on cellular lipid metabolism as compared to exogenous apoE. J774 macrophages, which do not express apoE, were engineered to express endogenous apoE by transfection of human apoE3 cDNA expression constructs (E(+)) or control vectors (E(-)) into the cells. To compare the effects of exogenous apoE and endogenous apoE on TGRP uptake, cells were incubated with or without apoE associated with (3)H-cholesteryl ether-labeled TGRP. Exogenous apoE enhanced TGRP uptake in both E(-) and E(+) cells. E(-) cells displayed significantly higher TGRP uptake than E(+) cells. Sodium chlorate, which inhibits cell proteoglycan synthesis, markedly diminished differences in TGRP uptake between E(-) and E(+) cells, suggesting that endogenous apoE-proteoglycan interaction contributes to differences in uptake between the two cell types. Particle uptake by the LDL receptor, by the LDL receptor related protein, or by scavenger receptors were similar between E(-) and E(+) cells indicating that endogenous apoE expression does not have a general effect on endocytic pathways. Exogenous apoE carried on TGRP stimulated TG utilization and CE hydrolysis in both cell types. However, TG utilization and CE hydrolysis were not affected by endogenous apoE expression. In conclusion, macrophage expression of apoE has very different effects on TGRP metabolism than exogenously supplied apoE. The fluorescence microscopy results in this study showing that exogenous apoE and endogenous apoE were confined in separate cellular compartments support the hypothesis that these differences resulted from distinct intracellular trafficking pathways followed by exogenous apoE bound to TGRP as compared to endogenous cell-expressed apoE.

Apolipoproteins E↗