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PubMed1990

Growth and development of brain of artificially reared hypoketonemic rat pups.

Three groups of rats were reared: mother-reared controls; artificially reared controls (AR-c), which were fed a milk substitute with the same composition of macro-nutrients as natural rat's milk; and an artificially reared test group (AR-h), which was fed a milk substitute identical to that fed AR-c pups except that the component of fat containing medium chain length fatty acids was omitted (medium chain triglyceride deficient) and replaced on an isocaloric basis with carbohydrate. The AR rats were fed the milk substitute from postnatal Day 5 until Day 17 by fitting them with gastric cannulas through which the milk could be infused automatically. The nutritional impact of the milk substitutes on growth and the integrity of the brain was assessed by a comparison of morphologic and biochemical markers. Pups in the AR-h group were hypoketonemic. Animals in all groups attained the same body weight by Day 17 and there was no difference in the morphologic markers among the groups with one exception: the vibrissal "barrel fields" of the somatosensory cortex of rat pups in both AR groups were reduced in size but not in number of distribution from those of the mother-reared groups. Furthermore, the brains of the rat pups in the AR groups were not different in weight, but they weighed less than brains of mother-reared controls. Our data show that although there are many similarities in the status of AR rat pups when compared with mother-reared controls, distinctive differences associated with artificial rearing are evident. We conclude that medium chain fatty acids in milk fat and the circulating ketone bodies are not mandatory substrates for growth and the development of the brain. Mechanisms must exist whereby alternative substrates are used to compensate when these metabolites are diminished in supply.

Animal Nutritional Physiological Phenomena↗
PubMed2005

Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle.

We previously localized a quantitative trait locus (QTL) on chromosome 6 affecting milk fat and protein concentration to a 4-cM confidence interval, centered on the microsatellite BM143. We characterized the genes and sequence variation in this region and identified common haplotypes spanning five polymorphic sites in the genes IBSP, SPP1, PKD2, and ABCG2 for two sires heterozygous for this QTL. Expression of SPP1 and ABCG2 in the bovine mammary gland increased from parturition through lactation. SPP1 and all the coding exons of ABCG2 and PKD2 were sequenced for these two sires. The single nucleotide change capable of encoding a substitution of tyrosine-581 to serine (Y581S) in the ABCG2 transporter was the only polymorphism corresponding to the segregation status of all 3 heterozygous and 15 homozygous sires for the QTL in the Israeli and U.S. Holstein populations. The allele substitution fixed effects on the genetic evaluations of 335 Israeli sires were -341 kg milk, +0.16% fat, and +0.13% protein (F-value = 200). No other polymorphism gave significant effect for fat and protein concentration in models that also included Y581S. The allele substitution effects on the genetic evaluations of 670 cows, daughters of two heterozygous sires, were -226 kg milk, 0.09% fat, and 0.08% protein (F-value = 394), with partial dominance towards the 581S homozygotes. We therefore propose that Y581S in ABCG2 is the causative site for this QTL.

ATP-Binding Cassette Transporters↗
PubMed1986

Detection of soybean in soy-based meat substitutes.

The statistical analysis of the available data indicated that the straight line equations of protein, fat, fibre, calcium, methionine, and lysine could successively be used for forecasting the added soy percent in a given recipe. On the other hand, the areas of the identified bands in the electropherograms of the investigated samples were considered a reasonable tool for the quantitative determination of whole soybean in soy-based meat substitutes.

Amino Acids↗
PubMed2002

Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition.

We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition--particularly fat content--to the centromeric end of bovine chromosome 14. We subsequently exploited linkage disequilibrium to refine the map position of this QTL to a 3-cM chromosome interval bounded by microsatellite markers BULGE13 and BULGE09. We herein report the positional candidate cloning of this QTL, involving (1) the construction of a BAC contig spanning the corresponding marker interval, (2) the demonstration that a very strong candidate gene, acylCoA:diacylglycerol acyltransferase (DGAT1), maps to that contig, and (3) the identification of a nonconservative K232A substitution in the DGAT1 gene with a major effect on milk fat content and other milk characteristics.

Acyltransferases↗
PubMed1999

A comparison of grain, oil and beet pulp as energy sources for the exercised horse.

High-grain diets for the exercising horse were compared with diets which provided 15% of the total caloric intake from either vegetable oil or a highly fermentable fibre source (beet pulp). Six Thoroughbreds age 3 years were fed one of 3 diets or 5 weeks in a replicated 3 x 3 Latin square. The CONTROL diet was 3.65 kg of sweet feed (SF), 0.9 kg of a protein/vitamin/mineral pellet and 5.45 kg of hay cubes. The FAT diet replaced 1.15 kg of SF with 0.45 kg of soybean oil and the FIBRE diet replaced 1.15 kg of SF with 1.36 kg of beet pulp. Horses were exercised 3 times per week on a high-speed treadmill. During the last week of each period, the horses performed a standardised exercise test (SET). A series of blood samples was drawn immediately before feeding and every 0.5 h for 3 h after feeding, throughout the exercise bout and 30 min post exercise. Plasma was analysed for lactate, glucose, cortisol, insulin, packed cell volume, total protein and triglycerides. Water intake was measured at regular intervals during SET day. Blood glucose was lower (P < 0.05) in the FAT-fed horses during the 3 h post feeding as compared to either CONTROL or FIBRE-fed horses. Insulin was lower (P < 0.05) in the FAT-fed both post feeding and throughout exercise. Cortisol was lower (P < 0.05) in the FAT than the CONTROL-fed during exercise. Following exercise, the FAT-fed drank more water (P < 0.01) than either CONTROL or FIBRE-fed. Substituting 15% of DE as vegetable oil had a greater effect on metabolic response to exercise than a 15% substitution of beet pulp.

Animal Feed↗
PubMed2003

Dietary monounsaturated versus polyunsaturated fatty acids: which is really better for protection from coronary heart disease?

PURPOSE OF REVIEW: The purpose is to evaluate recent findings concerning dietary fats and the risk of coronary heart disease. Monounsaturated fatty acids are often regarded as healthy, and many have recommended their consumption instead of saturated fatty acids and polyunsaturated fatty acids. Support for the benefits of monounsaturated fatty acids comes largely from epidemiological data, but they have not been an isolated, single variable in such studies. Beneficial effects on the plasma lipid profile and LDL oxidation rates have also been identified. More recent findings have questioned the impact of suspected beneficial effects on coronary heart disease, indicating that studies with more conclusive endpoints are needed. RECENT FINDINGS: Human dietary studies often produce conflicting results regarding the effects of monounsaturated and polyunsaturated fatty acids on the plasma lipid profile. Monounsaturated and polyunsaturated fatty acids both appear to reduce total and LDL-cholesterol compared with saturated fatty acids; however, the effect on HDL is less clear. Lowered HDL levels in response to low-fat or polyunsaturated fatty acid diets and the decreased protection from oxidation of polyunsaturated fatty acid-enriched LDL may not indicate increased coronary heart disease risk. Several lines of evidence also suggest that polyunsaturated fatty acids may protect against atherosclerosis. SUMMARY: Recommendations to substitute monounsaturated fatty acids for polyunsaturated fatty acids or a low-fat carbohydrate diet seem premature without more research into the effects on the development of atherosclerosis. Current opinions favoring monounsaturated fatty acids are based on epidemiological data and risk factor analysis, but are questioned by the demonstrated detrimental effects on atherosclerosis in animal models.

Cholesterol↗
PubMed1990

Treatment failure after substitution of generic pancrelipase capsules. Correlation with in vitro lipase activity.

Pancreatic enzyme products are formulated, manufactured, and sold without submitting efficacy or bioavailability data to the Food and Drug Administration because of a quirk in the law. We documented therapeutic failures in three patients with cystic fibrosis after pharmacists substituted generic pancrelipase capsules for the Pancrease brand. Gastrointestinal symptoms and fat malabsorption rapidly resolved after therapy was reinstituted with brand name products. In vitro analysis indicated that after 1 hour of exposure to simulated gastric fluid, lipase activity was less than 200 U per capsule from all three generic capsules dispensed to the patients compared with 6820 U per capsule from Pancrease. These data indicate that the enteric coating of the generic product was defective and that the substituted product was not bioequivalent to the prescribed brand. We conclude that the Food and Drug Administration should institute regulations over this group of products.

Adult↗
PubMed1983

Influence of chronic ethanol treatment on alpha1-adrenergic and vasopressin receptor-stimulated phosphatidylinositol synthesis in isolated rat hepatocytes.

Adult male rats were given nutritionally balanced high fat (34% corn oil) diets containing either ethanol or isocalorically substituted sucrose for 4-5 weeks. Phosphatidylinositol-phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine contents of whole hepatocytes were not altered in ethanol-treated rats. However, vasopressin and alpha1-adrenergic stimulation of [32P]-incorporation into phosphatidylinositol of isolated hepatocytes from ethanol-treated rats was increased substantially compared to that of controls. Yet, chronic ethanol treatment had no effect on hepatic alpha1 receptor density or affinity as measured by [3H]prazosin specific binding. These results suggest that the supersensitive phosphatidylinositol response to this alpha1 agonist observed in hepatocytes from ethanol-treated rats occurred distal to cell surface receptors and may be similar for vasopressin.

Alcoholism↗
PubMed2002

Patterns of PCBs and PCDD/PCDFs in chicken and pork fat following a Belgian food contamination incident.

A food contamination incident involving polychlorobiphenyls (PCBs) and PCDD/Fs occurred in 1999 in Belgium. On heavily affected farms, concentrations of PCBs in chicken or pork fat exceeded the Belgium tolerance limit of 200 ng/g lipid weight for the sum of seven marker PCBs. Analysis of contaminated samples showed that the patterns for PCB and PCDD/F congeners differed among feed, chicken fat and pork fat. Lower chlorinated PCBs and polychlorodibenzofurans (PCDFs) including those with high TEFs (PCBs 105, 118, 126 and 2,3,4,7,8-PeCDF) were shown to either bioaccumulate more in chicken fat or to be eliminated more readily in pork. This leads to the possibility that consumption of chicken would result in a higher TEQ human body burden than that from the same consumption of pork. In addition, PCDF congeners with non-2,3,7,8-substitution (e.g., 1,2,4,7,8-PeCDF) were present in chicken fat but absent in pork fat. Since the residue pattern in this commercial episode changes less in the avian species, these results reinforce the value of birds rather than mammals as markers of the source of contamination with persistent organochlorine pollutants.

Adipose Tissue↗
PubMedDate not supplied

Switching strategies to improve lipid profile and morphologic changes.

Metabolic alterations and body fat changes are well-recognized limitations of protease inhibitor-based regimens. Strategies of replacing protease inhibitors with nonnucleoside reverse transcriptase inhibitors or abacavir have been shown to improve metabolic abnormalities, particularly by decreasing cholesterol and triglyceride levels, and reducing cardiovascular risk. The various therapeutic options show differences in efficacy, tolerability, and metabolic outcomes. Abacavir seems to be better tolerated, at least in the only randomized trial in which the three options were compared face-to-face, but it is associated with higher virologic failure in patients with prior suboptimal nucleoside therapy. Nonnucleoside reverse transcriptase inhibitors, particularly nevirapine, result in a better lipid profile with a greater increase in HDL cholesterol and in the HDUtotal cholesterol ratio, one of the most important parameters associated with a reduction in cardiovascular risk. Efavirenz has been associated with increased triglyceride levels in some studies. Although protease inhibitor compounds as a family have been linked to metabolic and body fat alterations, new drugs such as atazanavir seem to be associated with a more favorable lipid profile. Lipoatrophy is a stigmatizing complication in HIV-infected patients receiving HAART. There is strong evidence suggesting a prominent role of thymidine analogs, mainly stavudine, in its development. Substitution of stavudine or zidovudine for abacavir or tenofovir partially improves peripheral fat loss. In addition, the lipid profile significantly improves. Finally, although the extended use of non-thymidine nucleoside analogs and the development of new families of antiretroviral drugs will probably result in a lower impact in lipids and morphologic changes, many patients are currently under treatment with these compounds. In this setting, switching strategies may be useful to minimize clinical and psychological consequences, improving the quality of life of HIV-infected patients treated with HAART.

Anti-HIV Agents↗
PubMed1976

Influence of carbohydrate source on liver fat accumulation in hens.

Four experiments were conducted with laying hens and one with broiler chicks to investigate the effect of carbohydrate source on fat accumulation in the liver. When corn and wheat in various proportions were fed to laying hens, the percent fat and total fat per liver increased as the proportion of corn increased. In comparison of different cereal grains and wheat samples in isocaloric diets, the total liver fat accumulated was the highest for hens fed grain sorghum, corn or triticale and the lowest for those fed barley, oats or rye. Intermediate levels of liver fat were obtained with wheat and similar liver fat contents were observed with hens fed different samples of West Coast wheat. There was no significant difference in liver fat of groups fed wheat diets made isocaloric with corn oil or animal fat, Liver fat accumulation of broiler chicks fed diets with corn or wheat was not significantly different. No difference in liver weight, liver fat content and total fat per liver was observed among hens fed diets containing either zero, one-half, or all glucose monohydrate substituted for corn. In comparisons of corn or wheat from different geographical area, no difference was observed in liver fat content of hens fed corn grown in Georgia or the Midwest or wheat grown in Georgia or in the Far West. Hens fed diets contaning corn had significantly more liver dry matter, liver fat, and total fat per liver than hens fed the isocaloric diets containing wheat. Considerably more fat accumulated in the livers of hens fed diets containing corn at Washington State University (15.4 to 19.6 g. fat/liver) than in hens fed corn at the University of Georgia (5.4 to 7.2 g. fat/liver), suggesting the existence of unidentified environmental factors affecting liver fat accumulation.

Animal Feed↗
PubMedDate not supplied

Validation and use of the CALUX-bioassay for the determination of dioxins and PCBs in bovine milk.

There is a strong need for the development of relatively cheap and rapid bioassays for the determination of dioxins and related compounds in food. A newly developed CALUX (Chemical-Activated LUciferase gene eXpression) bioassay was tested for its possible use to determine low levels of dioxins in bovine milk. Data show that this mammalian cell-based test is very sensitive for 2,3,7,8-substituted dioxins and related PCBs, thereby reflecting the relative potencies of these compounds in comparison to TCDD (TEF-values). The limit of detection was about 50 fg of TCDD. Furthermore, the response obtained with a mixture of dioxins was additive, in accordance with the TEF-principle. Milk fat was isolated by centrifugation followed by clean-up of the fat with n-pentane, removal of the fat on a 33% H2SO4 silica column, and determination of Ah receptor agonist activity with the CALUX-bioassay. An equivalent of 67 mg fat was tested per experimental unit, resulting in a limit of quantification around 1 pg i-TEQ/g fat. To investigate the performance of the method, butter fat was cleaned and spiked with a mixture of 17 different 2,3,7,8-substituted PCDD and PCDF congeners at 1, 3, 6, 9, 12 and 15 pg TEQ/g fat, as confirmed by GC/MS. In this concentration range, the method showed a recovery of TEQs around 67% (58-87%). The reproducibility, determined in three independent series showed a CV varying between 4% and 54%, with the exception of the sample spiked at 1 pg i-TEQ (CV 97%). The repeatability determined with the sample spiked at 6 pg i-TEQ/g showed a CV of 10%. Testing of 22 bovine milk samples, taken at different sites in The Netherlands, in the CALUX-assay showed combined dioxin and dioxin-like PCB levels equivalent to 1.6 pg TCDD/g fat (range 0.2-4.6). GC/MS analysis of these samples revealed an average level of 1.7 pg i-TEQ/g fat, varying between 0.5 and 4.7 pg i-TEQ/g fat. All five samples showing a GC/MS determined dioxin content of more than 2 pg i-TEQ/g fat gave a response in the CALUX-assay corresponding to more than 2 pg TCDD/g fat. These data clearly show that the CALUX-bioassay is a promising method for the rapid and low cost screening of dioxins in bovine milk.

Animals↗
PubMed2000

[Senile hypogonadism in man and hormone replacement therapy].

Aging is accompanied by a progressive decline of testicular function. Whereas fertility persists until a very old age, endocrine function declines progressively and at age 70 yrs, more than 25% of men have hypogonadal testosterone levels. This decline in testosterone plays an important role in a series of signs and symptoms that accompany the aging process such as a decline in virility, in libido and sexual activity, muscle mass and strength, decline in bone mass (osteoporosis), an increase in abdominal fat mass and a decrease in the feeling of general well being. Most of these signs and symptoms have a multifactorial origin, nevertheless, androgen substitution generally improves most of these symptoms, increasing muscle mass and strength, improving libido and sexual activity, decreasing abdominal fat and improving insulin sensitivity as well as the sense of well being, effects which suggest a role of androgen deficiency in their genesis. Side effects of this substitutive therapy, mainly at the level of the prostate, with possible stimulation of a prostatic carcinoma, should be carefully looked for. Before starting any androgen therapy, the presence of a prostatic carcinoma should be excluded by rectal examination and PSA measurement, eventually, in case of doubt, complemented by transrectal echography. Presence of a prostatic carcinoma is an absolute contraindication for androgen therapy. During treatment, development of side effects should be traced by a six monthly rectal examination and PSA determination as well by monitoring of hematocrit and lipid profile.

Aged↗
PubMed1996

Covert manipulation of the ratio of medium- to long-chain triglycerides in isoenergetically dense diets: effect on food intake in ad libitum feeding men.

OBJECTIVE: This study examined whether isoenergetic substitution of MCT for LCT in HF, HE diets (639 kJ/100 g) limits the excess energy intakes frequently observed on high-fat diets of high energy density (HF, HE). SUBJECTS: Six healthy male volunteers [mean age (SD) = 27.17 (4.17 y) mean weight = 63.33 (7.33 kg), mean height = 1.72 (0.05 m)]. DESIGN: The subjects were each studied three times during 14 d throughout which they had ad libitum access to one of three covertly-manipulated diets, which were randomly assigned in a counter-balanced design. The fat, carbohydrate (CHO) and protein in each diet (as percent energy) were identical at 62:28:10, with 2 day maintenance (1.5 x BMR, MF) beforehand. The ratio of MCT to LCT was 1:2, 1:1 and 2:1 on the low-, (LMCT) medium- (MMCT) and high-MCT (HMCT) diets, respectively. Within each diet every item was of the same composition and offered as a 3 day rotating menu. RESULTS: Energy intakes were significantly lower on the HMCT diet [F (2,240) = 7.52; p < 0.001] giving mean values of 13.50, 13.67, and 12.43 MJ/d on the LMCT, MMCT and HMCT diets, respectively. Food intake followed a parallel trend. By day 14 body weight changes amounted to +0.45, +0.41 and -0.03 kg, respectively. CONCLUSION: These data suggest that substitution of a readily metabolised fat for a less readily metabolised fat, in very high fat diets can limit the excess energy intakes and weight gain that is usually produced by HF, energy-dense diets.

Adult↗
PubMed2005

A statistical approach based on substitution of macronutrients provides additional information to models analyzing single dietary factors in relation to type 2 diabetes in danish adults: the Inter99 study.

Most studies analyzing diet-disease relations focus on single dietary factors rather than combining different nutrients into the same statistical model. The objective of this study was to identify dietary factors associated with the probability of having diabetes identified by screening (SDM) in Danish men and women aged 30-60 y. A specific objective was to examine whether an alternative statistical approach could provide additional information to already existing statistical approaches used in nutritional epidemiology. Baseline data from the Danish population-based Inter99 study were used. The dietary intake of 262 individuals with SDM was compared with that of 4627 individuals with normal glucose tolerance (NGT) using 2 different types of multiple logistic regression models adjusted for potential confounders. The first model included single dietary factors, whereas the second model was based on substitution of macronutrients. In the models with single dietary factors, high intakes of carbohydrates, dietary fiber, and coffee were inversely associated with SDM (P < 0.01), whereas high intakes of total fat and saturated fat were positively associated with SDM (P < 0.05). A modest U-shaped association was found between alcohol consumption and SDM (P = 0.10) [corrected] Results from the substitution model showed that when 3% of energy (En%) as carbohydrate replaced 3 En% fat or alcohol, the probability of having SDM decreased by 9 and 10%, respectively (P < 0.01) [corrected] No other macronutrient substitutions resulted in significant associations. Hence, the statistical approach based on substitution of macronutrients provided additional information to the model analyzing single dietary factors.

Adult↗
PubMed2005

Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis.

Type 2 diabetes is a disorder of hyperglycemia resulting from failure of beta cells to produce adequate insulin to accommodate an increased metabolic demand. Here we show that regulation of mRNA translation through phosphorylation of eukaryotic initiation factor 2 (eIF2alpha) is essential to preserve the integrity of the endoplasmic reticulum (ER) and to increase insulin production to meet the demand imposed by a high-fat diet. Accumulation of unfolded proteins in the ER activates phosphorylation of eIF2alpha at Ser51 and inhibits translation. To elucidate the role of this pathway in beta-cell function we studied glucose homeostasis in Eif2s1(tm1Rjk) mutant mice, which have an alanine substitution at Ser51. Heterozygous (Eif2s1(+/tm1Rjk)) mice became obese and diabetic on a high-fat diet. Profound glucose intolerance resulted from reduced insulin secretion accompanied by abnormal distension of the ER lumen, defective trafficking of proinsulin, and a reduced number of insulin granules in beta cells. We propose that translational control couples insulin synthesis with folding capacity to maintain ER integrity and that this signal is essential to prevent diet-induced type 2 diabetes.

Amino Acid Substitution↗
PubMed2005

Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.

It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.

Adipose Tissue↗
PubMed1998

Effect of the Pro12Ala variant of the human peroxisome proliferator-activated receptor gamma 2 gene on adiposity, fat distribution, and insulin sensitivity in Japanese men.

To examine the role of the Pro12Ala variant of the human PPARgamma2 gene on adiposity and insulin resistance, we studied the effect of the variant on fat distribution assessed by CT scan, plasma glucose, and insulin levels during a 75g oral glucose load in 215 non-diabetic Japanese men. The allele frequency of the variant was 0. 03 in this population. There were no differences in body mass index (BMI), subcutaneous fat area (S), visceral fat area (V), V/S ratio, fasting plasma insulin levels, or insulin resistance index in homeostatic model assessment between 203 subjects who were homozygous for the wild-type Pro12 allele and 12 subjects with the variant Ala12 allele (11 heterozygotes and one homozygote). These data suggest that the Pro12Ala variant is not a major contributor to adiposity, fat distribution, or insulin resistance in Japanese men.

Adipose Tissue↗