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Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group.

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.

Adult↗

Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The Deflazacort Study Group.

Kidney function, growth velocity, weight/height ratio, body composition, lipid profile, and bone mass were studied in a randomized, multicenter trial of deflazacort versus methylprednisone in 27 prepubertal patients with kidney transplantation. Methylprednisone (0.20+/-0.03) was replaced by deflazacort (13 patients, 0.30+/-0.03 mg/kg per day). After 12 months, creatinine clearance decreased significantly only during methylprednisone therapy. Growth velocity increased only in patients treated with deflazacort from 3.3+/-0.6 to 5.6+/-0.5 cm/year. Serum levels of several components of the insulin-like growth factor axis did not change. Weight/height ratio was increased in methylprednisone-treated patients (P<0.05) and decreased in deflazacort-treated patients (P<0.005). Lean body mass increased in both groups (P<0.005). Fat body mass and serum leptin increased only in methylprednisone-treated patients (P<0.025). Total cholesterol and low-density lipoprotein-cholesterol increased in methylprednisone-treated patients by 9.9% (P<0.05) and 12.5% (P<0.025). High-density lipoprotein-cholesterol increased by 21% (P<0.005) and apolipoprotein B decreased by 11% (P<0.005) in deflazacort-treated patients. Total skeleton and lumbar spine bone mineral density decreased in both groups, but at 1 year methylprednisone-treated patients had lost 50% more bone. Bone mineral content decreased only in methylprednisone-treated patients (P<0.01). Our data suggest that substituting deflazacort for maintenance methylprednisone might prevent height loss, excessive bone loss, and fat accumulation; and leads to an improvement in the lipoproteins of these children.

Body Composition↗

Effects of dietary 1,3-butylene glycol on adipose tissue metabolism from lean and obese swine.

One,three-butylene glycol (BG) was isocalorically substituted for glucose and fed ad libitum to lean (XB) and obese (HL) swine at 0, 10, and 20% of the total dietary ME from 25 kg body weight until slaughter at 90 kg. BG depressed rate and efficiency of gain in both groups. Plasma beta-hydroxybutyrate concentration was increased by the ketogenic energy substitution. Plasma glucose and free fatty acids were not influenced by diet composition. Adipose tissue utilization of glucose for lipogenesis was depressed by BG in both XB and HL animals after 4 wk of treatment. Insulin added in vitro increased glucose utilization by approximately 20% in adipose tissue from both breed groups; however, the BG induced depression of glucose utilization for fatty acid synthesis was still evident. Insulin-stimulated glucose utilization was greater in XB then in L swine. After 12 wk of dietary treatment, animals given BG had significantly increased plasma insulin concentration and decreased plasma urea concentrations. Although the absolute rates of lipogenesis had decreased after 12 wk of treatment, similar diet-related results were obtained. Insulin did not stimulate glucose utilization by adipose tissue from animals of either breed group at this latter sampling. Fatty acid esterification was slightly depressed by BG at the 4 wk sampling, but after 12 wk of treatment, only a significantly breed group effect was evident. Subcutaneous fat thickness, loineye area and carcass percentage lean cuts were not influenced by diet composition. This experiment demonstrated that ketogenic energy and substitution in the diet does depress the rate of de novo lipogenesis from glucose as measured by in vitro incubation of swine adipose tissue. Supplementation of the incubation media with massive quantities of insulin did not reverse the dietary treatment effects, and animals of both lean and obese phenotypes responded similarly to the dietary treatment. The absence of dietary treatment effects on indices of body fat content suggest that ketone bodies may be substituted for glucose as a lipogenic substrate in swine.

3-Hydroxybutyric Acid↗

A potential molecular marker for selection against abdominal fatness in chickens.

The peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was investigated as a candidate gene for growth and fatness traits in chicken because of its prominent role in muscle fiber specialization and adipogenesis. A single nucleotide polymorphism (SNP) from G to A at position 646 of the open reading frame of chicken PGC-1alpha gene causing an Asp216Asn amino acid substitution was identified. The frequencies of alleles and genotypes were significantly different among 6 chicken breeds (P < 0.01). The White Plymouth Rock had the highest frequency (0.67) of allele G, whereas the White Leghorn had the lowest (0.18). The associations of the SNP with the growth and fatness traits were evaluated in 332 F(2) birds from an experimental cross of White Plymouth Rock x Silkies. No association was found between the SNP and growth-related traits. However, abdominal fat weight at 12 wk of age for birds with genotype GG was 34.26 and 28.71% higher than those with genotypes AA and AG, respectively (P < 0.01), indicating that the Asp216Asn polymorphism of the PGC-1alpha gene could be used as a novel potential molecular marker for selection against abdominal fatness without interfering in regular breeding for growth rate of chickens.

Abdominal Fat↗

Phenotypic heterogeneity in body fat distribution in patients with atypical Werner's syndrome due to heterozygous Arg133Leu lamin A/C mutation.

CONTEXT: A heterozygous missense mutation substituting arginine at position 133 to leucine in the lamin A/C protein has been reported in two young women with clinical features of short stature, bird-like faces, and early onset of aging processes. OBJECTIVE: The objective of the study was to carry out detailed phenotyping of these two women by evaluating the pattern of fat loss using anthropometry, dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI) and study metabolic abnormalities in glucose and lipid metabolism. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at a referral center. PATIENTS: Patient 1 was a 23-yr-old African-American female with progeroid features. Patient 2 was a 24-yr-old Caucasian female with generalized lipodystrophy, hypertriglyceridemia, and severe insulin resistance diabetes who required more than 200 U of insulin daily. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Body fat distribution to characterize pattern of lipodystrophy and nuclear morphology abnormalities in skin fibroblasts were studied. RESULTS: Patient 1 had normal body fat (27%) by DEXA. However, MRI revealed relative paucity of sc fat in the distal extremities, with preservation of sc truncal fat. She had impaired glucose tolerance and elevated postprandial serum insulin levels. Patient 2, in contrast, had only 11.6% body fat as determined by DEXA and had generalized loss of sc and intraabdominal fat on MRI. Skin fibroblasts from patient 2 showed marked abnormal nuclear morphology, compared with those from patient 1. Despite the deranged nuclear morphology, the lamin A/C remained localized to the nuclear envelope, and the nuclear DNA remained within the nucleus. CONCLUSIONS: Atypical Werner's syndrome associated with Arg133Leu mutation in the LMNA gene presents with a phenotypically heterogeneous disorder. Furthermore, the severity of metabolic complications seems to correlate with the extent of lipodystrophy.

Adipose Tissue↗

Beneficial effect of hormone replacement therapy on weight loss in obese menopausal women.

OBJECTIVE: At the onset of menopause, weight-gain and the aggravation of certain cardiovascular risk factors are frequently observed. The aim of this study was to examine the metabolic effects of combined hormone replacement therapy (17beta-oestradiol transdermic 50 microg for 21 days and oral medroxyprogesterone acetate 5 mg from day 10 to 21) using, in particular, indirect calorimetry. METHODS: Patients (21; 12 substituted and nine controls) were studied twice (3 months apart) during an oral glucose load (75 g). RESULTS: Total body weight was unaltered after 3 months in the control group, whereas a fat-loss of 2.1+/-0.2 kg and a decrease of the waist:hip ratio were observed in the substituted group. In the latter group, a significant increase in lipid oxidation was observed (0.58+/-0.06 mg/kg/min before and 0.75+/-0.04 mg/kg/min after substitution P<0.05), whilst total energy expenditure and thermogenesis were also increased. Glucose, lipid and protein oxidation remained stable during three months in the control group. The insulin response to an oral glucose load diminished by 30% with hormone replacement therapy (102.3+/-32.8 mmicro/l versus 71.4+/-20.0 mmicro/l). Total and LDL-cholesterol improved after hormone replacement therapy whereas plasma triglycerides were not altered. CONCLUSIONS: Combined hormone replacement therapy not only prevented weight-gain, but favored weight-loss by significantly increasing lipid oxidation after 3 months of treatment. It also favourably influenced the insulin response, plasma lipids and energy expenditure.

Cholesterol↗

Specific distribution of short-chain fatty acids in molecular distillates of bovine milk fat.

Triglycerides with a total of 34-44 acyl carbon atoms have previously been shown to account for nearly 50% of bovine milk fat. About 80% of this material was isolated by molecular distillation and a representative fraction of these glycerides was subjected to a stereospecific analysis. Of the 29 moles % of C(4)-C(8) fatty acids present in the analyzed fraction, at least 95% were specifically attached to the glycerol molecule in the position corresponding to carbon 3 of sn-glycerol 3-(dihydrogen phosphate) (L-alpha-glycerophosphate). The distribution of the other fatty acids (C(10) or greater) did not show such marked specificity for either the 1- or the 2-position. The data support the hypothesis that the short-chain fatty acids are esterified with long-chain diglycerides, or are substituted in glycerophosphatide intermediates, during the final step in the biosynthesis of milk fat triglycerides.

Animals↗

Stimulation of immune reactivity by methoxy-substituted glycerol ethers incorporated into the feed.

In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes.

Animals↗

Effects of androgen replacement on metabolism and physical performances in male hypogonadism.

Hypogonadism in men is associated with decreased physical performance. This phenomenon depends on significantly measurable adverse traits in body composition, namely increased body fat content and reduced muscle mass. Physical abilities in hypogonadal men are further hampered by lower oxygen supply due to decreased hemoglobin concentrations and by poor glucose utilization. In addition, dysthymia and lack of necessary aggressiveness contribute to further deterioration of physical features. T substitution can improve lipid and insulin metabolism, resuiting in changes of body composition, such as decreasing fat depots. Growth of muscle fibers can also be observed. Stabilization of the musculo-skeletal system by increased bone density will further contribute to increased physical fitness, reflected by increased strength and endurance. Treatment outcome is strongly influenced by age and training. The issues reviewed strongly support T treatment of hypogonadal men accompanied by regular monitoring.

Body Composition↗

Measurement of the ultrasonic attenuation of fat at high frequency.

RATIONALE AND OBJECTIVES: High-frequency ultrasound devices are often limited by a decreased depth of acoustic imaging caused by the increased attenuation of tissue at high frequencies. We investigated the role of adipose tissue in this phenomenon. METHODS: A substitution technique was used to calculate the ultrasonic attenuation (decibels per centimeter) of fresh samples of sheep rumen, omental fat, and back fat and swine back fat and various concentrations of bovine milk fat at 22 degrees C and 37 degrees C for frequencies of 15 and 20 MHz. RESULTS: The attenuation was significantly higher for sheep adipose tissue than for the intestinal wall, in descending order, omental fat, back fat, and rumen wall (P < 0.01). A correlation was found between bovine milk fat concentrations and attenuation at both frequencies (R2 > 0.9). The attenuation of adipose tissues decreased significantly with an increase in temperature (P < 0.01), whereas the attenuation of sheep rumen showed no significant change (P > 0.1). CONCLUSIONS: The ultrasonic attenuation of fat may contribute to limitations on the use of high-frequency ultrasound in clinical situations in which adipose tissue is present.

Adipose Tissue↗

Role of genetic variation at the apo AI-CIII-AIV gene cluster in determining plasma apo AI levels in boys and girls.

We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (-75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8-11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II-CIII) and the apo CIII-AIV intergenic region (Pvu II-AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V-V+ of the G/A substitution and the PvuII-AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V-V-. In girls, however, there was evidence of significant interaction of effects between the PvuII-AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V+) of the PvuII-AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII-CIII and PvuII-AIV polymorphisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

Characteristics of adipose tissue growth in broiler-type chickens to 22 weeks of age and the effects of dietary protein and lipid.

Female broiler-type chickens were fed diets containing different concentrations of protein and fat in two experiments. The first experiment was for 4 weeks. The mean weights of the abdominal fat pads were inversely related to dietary concentrations of protein between 20 and 35%. Adipocyte size and cellularity of the fat pads were lower with 30 than 20% protein. Fat deposition in the abdominal pad was increased in 3-week-old chicks by isocaloric substitution of oil for starch in the diets. At 4 weeks of age the effect of oil was not significant with 30 or 20% dietary protein (no measurements were made in chicks fed 35 or 25% protein). In Experiment 2, the development of the abdominal fat pad in birds fed 18 to 33% protein was monitored for 22 weeks. By 7 weeks the distribution of adipocyte size was bimodal. The initial adipocyte population showed comparatively little increase in numbers after 12 weeks, but cell size continued to increase. The numbers of adippcytes in the second population of adipocytes was still increasing rapidly at 22 weeks, although the size of the cells in this population remained small. At 22 weeks the small cells constituted 62% of the total adipocyte population but contained only 2.4% of the lipid in the fat pad. Adipocyte cell size was significantly affected by dietary protein and energy until 9 weeks of age, but the effects subsequently declined.

Abdomen↗

[Nutritional status in uremic patients treated with continuous ambulatory peritoneal dialysis. Relation with 1 year's evolution].

BACKGROUND: Signs of malnutrition have been detected in patients with chronic renal failure and a possible relation with complications of the disease has been speculated. The aim of the present study was to analyze the nutritional status of a group of patients with the aforementioned diagnosis on a substitutive treatment program with outpatient continuous peritoneal dialysis (CAPD) and its relation with complications over one year. METHODS: The nutritional status of 29 of these patients and 22 individuals with normal renal function (controls) with global parameters of body fat, muscular protein and visceral protein being evaluated. The study was repeated at 6 and 12 months after the initial evaluation. The incidence of mortality, need for hospital admission because of complication and episodes of clinical peritonitis were analyzed. RESULTS: More than 70% of the patients presented protein-caloric malnutrition to a greater or lesser degree. This percentage dit not modify throughout the study and was produced at the expense of visceral protein, additionally affecting the fat and muscular protein of the males. Mortality, need for admission and the number of cases of peritonitis were greater in those presenting the lowest fat parameters with these complications beings foreseen from determined fat values. CONCLUSIONS: These patients have malnutrition which is related with the complications in the course of substitutive therapy making surveillance and nutritional support necessary.

Adult↗

Body composition, energy utilization, and nitrogen metabolism with a severely restricted diet supplemented with dihydroxyacetone and pyruvate.

To determine the effect of dietary modification on energy utilization during severely restrictive hypocaloric feeding, we measured body composition, energy deficit, and nitrogen metabolism in 13 obese women housed in a metabolic ward consuming a 2.1-MJ diet for 21 d with the three-carbon compounds dihydroxyacetone and pyruvate (DHAP), partially, isocalorically substituted for glucose. Body composition and amino acid (leucine) oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from metabolic rates and compared with weight and fat loss. Subjects fed dihydroxyacetone and pyruvate showed a greater weight loss (DHAP = 6.5 +/- 0.3 kg, P = 5.6 +/- 0.2 kg), fat loss (DHAP = 4.3 +/- 0.2 kg, P = 3.5 +/- 0.1 kg), and weight and fat loss/4.25-MJ deficit (P less than 0.05 for all determinations). Nitrogen balance (urine and stool) and leucine metabolism were similar in both groups. We conclude that partial substitution of DHAP for six-carbon compounds of a 2.1-MJ diet will increase weight and fat loss.

Adult↗

Superwarfarin poisoning: a report of two cases and review of the literature.

Superwarfarins are anticoagulant rodenticides similar to warfarin, but which have various substituted phenyl groups replacing the terminal methyl group, resulting in a fat-soluble, long-acting anticoagulant that is nearly 100 times more potent than the parent compound. Since their development, many accidental and intentional cases of consumption have been reported. We describe two cases of consumption, one related to unknown etiology, and the other related to utilization of the superwarfarin to potentiate a drug of abuse. The clinical manifestations including bleeding symptoms and abnormal coagulation assays are discussed. The differential diagnosis is quite broad, and includes all causes of vitamin K deficiency, factor deficiency or inhibitor, disseminated intravascular coagulation (DIC), and liver disease. Differentiating superwarfarin ingestion from the other causes can be quite difficult, but extremely important, as management requires prolonged administration of vitamin K. Other treatment options are discussed as well including, fresh frozen plasma (FFP), and recombinant factor VIIa. Finally, the significance of "lacing" drugs of abuse with superwarfarin to potentiate their effect is discussed, as well as the complications that could develop from such a habit.

4-Hydroxycoumarins↗

Effects of soy protein and casein in low cholesterol diets on plasma lipoproteins in normolipidemic subjects.

Dietary plant proteins may lower plasma cholesterol and LDL concentrations in hypercholesterolemic patients when substituted for animal proteins, particularly in diets with low cholesterol and saturated fat content. Plant protein diets appear, however, to be without effect on plasma lipoprotein levels in normal subjects. In the present study, we have examined whether the origin of the dietary protein, i.e. plant (soy) or animal (casein), affects the plasma lipoproteins in normolipidemic subjects when these proteins are presented as components of diets low in cholesterol and saturated fat. The study followed a crossover design. Five men and 5 women consumed liquid formula diets containing 20% of calories as casein or soy protein, 28% as fat (mainly monounsaturated), and 52% as carbohydrate; the intake of cholesterol was less than 100 mg per day. The two dietary periods, each of 1 month duration, were separated by an interim period of 1 month on self-chosen food. Following an initial 30% reduction of cholesterol and LDL plasma levels on both diets, the concentrations of each of the major lipoprotein classes (VLDL, IDL, LDL, HDL2 and HDL3) were similar during the two experimental dietary periods. Body weights were essentially constant. Dietary soy protein and casein could not be distinguished in their effects on the plasma concentrations and chemical composition of the major lipoprotein classes in normolipidemic subjects.

Adult↗

A high-stearic acid diet does not impair glucose tolerance and insulin sensitivity in healthy women.

Results in epidemiological and experimental studies suggest that a diet rich in saturated fat may affect insulin sensitivity. However, no published data are available on the effect of stearic acid in this respect. Therefore, we examined the effects of a high-stearic acid diet and a high-oleic acid diet on glucose metabolism, serum lipids and lipoproteins, and blood coagulation factors in 15 healthy female subjects. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 36% of energy (E%) as fat. In the experimental diets, 5 E% stearic or oleic acid was substituted for 5 E% of saturated fatty acids in the baseline diet. After the experimental diets, no differences were found in the insulin sensitivity index (mean+/-SEM, 5.4+/-1.9 v 5.2+/-1.6 x 10(-4) min(-1) x microU(-1) x mL(-1), nonsignificant [NS]), glucose effectiveness (0.026+/-0.006 v 0.026+/-0.003 min(-1), NS), or first-phase insulin reaction ([FPIR] 368+/-57 v 374+/-66 mU/L x min, NS). The concentration of serum lipids and lipoproteins and blood coagulation factors did not differ after the diet periods. In conclusion, a diet rich in stearic acid did not deteriorate glucose tolerance or insulin action in young healthy female subjects as compared with a diet rich in oleic acid.

Adult↗