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PubMed1970

The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm.

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.

Acetates↗
PubMed1976

Exchangeable and total calcium pools in mitochondria of rat epididymal fat-pads and isolated fat-cells. Role in the regulation of pyruvate dehydrogenase activity.

1. Isolated fat-cells and intact epididymal fat-pads were incubated in medium containing 45Ca2+ and the incorporation of 45Ca into mitochondrial and extramitochondrial fractions was studied. Redistribution of 45Ca between these fractions was essentially prevented by the addition of EGTA [ethanedioxybis(ethylamine)tetra-acetate] and Ruthenium Red to the sucrose-based extraction medium. 2. Incorporation of 45Ca into mitochondrial fractions of both fat-cells and fat-pads was found to be complete within 2-5 min, suggesting that mitochondria contain a pool of calcium in rapid isotopic exchange with extracellular Ca2+. This pool was about 20 times larger in mitochondria within fat-cells than within fat-pads. In fat-cells, 45Ca incorporation into the mitochondrial fraction accounted for about 34% of the total 45Ca incorporation into cells after 20 min and about 50% of the total mitochondrial calcium content measured by atomic absorption; values in fat-pads were about 7 and 20% respectively.

Adipose Tissue↗
PubMed2001

Ability of fat and fat-free mass percentages to predict functional disability in older men and women.

OBJECTIVES: Previous studies suggest an association between body composition and declining functional ability in older people. This study examined the relation between functional disability and percentage of fat mass (FM) and percentage of fat-free mass (FFM) in older men and women. DESIGN: Cross-sectional and prospective. SETTING: Rancho Bernardo, California. PARTICIPANTS: Subjects consisted of 1,051 ambulatory, community-dwelling Caucasian men and women, age 55 to 92, who attended a clinic visit between 1988 and 1992 and a subsequent clinic visit between 1992 and 1996. MEASUREMENTS: Measured at both visits, percentage of fat mass and percentage of lean body mass were estimated by bioelectric impedance analysis and functional disability was ascertained by self-administered questionnaire. Functional disability was dichotomized into those having any difficulty with a set of tasks versus those having no difficulty with the tasks. Two measures of functional disability were used: "lower body" disability, consisting of two lower motor tasks (walking 2-3 blocks and climbing up 10 stairs) and "overall" disability, consisting of nine tasks representing upper and lower body function and mobility. RESULTS: Compared with men, women were more likely to report both lower body and overall functional disability (P=.001). Cross-sectionally, a significant positive association was shown between fat mass and overall functional disability and a significant negative association was shown between FFM and overall functional disability in both men and women. Prospectively, increased percentage of body fat and decreased percentage of FFM were significantly associated with decreased functional ability in both women and men. All results were adjusted for age, smoking, alcohol use, physical activity, current estrogen use, depression, chronic disease, and education. CONCLUSION: Increased percentage of fat mass and decreased percentage of FFM are associated with greater functional disability in older men and women. Further research is needed to assess the relative importance of decreasing fat percentage or increasing fat-free percentage to preserve or improve functional ability in older people.

Adipose Tissue↗
PubMed2000

Subcutaneous central fat is associated with cardiovascular risk factors in men independently of total fatness and fitness.

The purpose of this study was to analyze the single and independent associations of whole body composition and fat distribution with cardiovascular disease (CVD) risk factors and fitness in middle-aged men. Sixty-two healthy Caucasian men (37.6 +/- 2.9 yr, 81.8 +/- 11.3 kg, 171.5 +/- 4.9 cm) participated in the study. Dual-energy x-ray absorptiometry (DXA) was used to assess total and regional body composition. The triceps, biceps, midthigh, calf, subscapular, chest, abdominal and suprailiac skinfolds, and the waist, hip and midthigh circumferences, and sagittal diameter were estimated. Cardiovascular fitness was estimated with a submaximal test. Bivariate and partial correlation analysis were used to study the association of total body percent fat (%fat), DXA trunk fat and trunk skinfolds (sum of subscapular, chest, abdominal, and suprailiac) and fitness with insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein AI (apo AI), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and diastolic and systolic blood pressure. All anthropometric and DXA body composition variables were significantly correlated with TC/HDL-C (from .26 to .50, P < .05). Similar relationships were found for insulin, HDL-C, and systolic blood pressure (r from .26 to .47, P < .05). Cardiovascular fitness was significantly (P < .05) associated with insulin (r = -.36), HDL-C (r = .27), TC/HDL (r = -.27), and with systolic blood pressure (r = -.37). After controlling for trunk skinfolds, none of the anthropometric and DXA body composition variables were correlated with any of the CVD risk factors. Similarly, when controlling for trunk skinfolds, cardiovascular fitness was not related to any of the metabolic variables. After adjusting for %fat, DXA trunk fat, and cardiovascular fitness, trunk skinfolds remained significantly (P < .05) related to insulin (r = .35), HDL-C (r = -.40), TC/HDL-C (r = .43), and apo AI (r = -.39). In conclusion, this study suggests that subcutaneous truncal fat, as estimated by skinfolds, is an independent predictor of CVD risk factors, and that the association between cardiovascular fitness and these risk factors may be mediated by the levels of abdominal subcutaneous fat in Caucasian middle-aged men.

Adipose Tissue↗
PubMed2002

The effects of birth weight and postnatal linear growth retardation on body mass index, fatness and fat distribution in mid and late childhood.

OBJECTIVE: To determine the effects of birth weight and early childhood stunting on body mass index (BMI), body fat and fat distribution at ages 7 and 11 years, and the change from 7 to 11 years. DESIGN: Prospective cohort study SETTING: Kingston, Jamaica. SUBJECTS: One hundred and sixteen stunted children (height-for-age below two standard deviations (<-2SD) of the National Center for Health Statistics (NCHS) references) and 190 non-stunted children (height-for-age > -1SD), identified at age 9-24 months. The stunted group was divided into a previously stunted group (height-for-age at 11 years >or= -1SD) and a chronically stunted group (height-for-age < -1SD). RESULTS: Birth weight was positively related to the children's BMI but not to measures of body fat. Birth weight was negatively associated with the subscapular/triceps skinfold (SSF/TSF) ratio at age 11 years, and to the change between 7 and 11 years. Controlling for birth weight, the chronically stunted group remained significantly smaller than the non-stunted children at both ages and increased less from 7 to 11 years in all measures except the SSF/TSF ratio, which was significantly greater at age 7 years. The previously stunted group had significantly lower BMI and percentage body fat at age 7 years than the non-stunted group. Change from 7 to 11 years was not significantly different from that of the non-stunted group except for a smaller increase in TSF. At age 11 years they had significantly lower TSF and percentage body fat. CONCLUSIONS: Children stunted in early childhood had less fat and lower BMI than non-stunted children but had a more central fat distribution that was partially explained by their lower birth weights. The association between birth weight and central fat distribution developed between 7 and 11 years.

Anthropometry↗
PubMed1987

Fatness and fat patterns: associations with plasma lipids and blood pressures in adults, 18 to 57 years of age.

As a part of the Fels Body Composition Study (an extension of the Fels Longitudinal Study in Yellow Springs, Ohio), the hypothesis was examined that a centripetal fat pattern, characterized by a greater proportion of trunkal than extremity adiposity, was associated independent of age and per cent body fat with levels of plasma lipids and lipoprotein cholesterols and blood pressures. A cross-sectional sample of 303 white men and women, 18 to 57 years of age, measured between September 1976 and August 1979, was selected without regard to diagnosis of hypertension, hyperlipidemia, or obesity. The degree of centripetal adipose tissue distribution was indexed by the logarithm of the ratio of the subscapular to lateral calf skinfold thicknesses. Per cent body fat was estimated by densitometry. In multiple regression equations controlling for age, age2, and per cent body fat, centripetal fat pattern had a small but significant positive association with systolic blood pressure in men (R2 = 0.02, p less than 0.05). In women, centripetal fat pattern had small but significant positive associations with plasma triglycerides (R2 = 0.05, p less than 0.005), and a significant negative association with plasma high density lipoprotein cholesterol (R2 = 0.08, p less than 0.0005) after effects due to age, age2, and per cent body fat had been removed. Centripetal fat patterns appear to be associated with an "atherogenic" lipid profile in women, but the association in men is confounded with effects due to age and total body adiposity.

Adipose Tissue↗
PubMed1997

Influence of soft tissue (fat and fat-free mass) on ultrasound bone velocity: an in vivo study.

RATIONALE AND OBJECTIVES: The authors determine the relative effect of soft-tissue compartments, body fat (percent [%Bfat] and weight [Bfat kg]) and fat-free mass (FFM kg), on measurements of ultrasound bone velocity (UBV m/second). METHODS: The authors measured UBV in proximal phalanxes and body fat and fat-free mass by near infrared interactance in 40 healthy premenopausal women (mean age +/- standard deviation 28.2 +/- 3.8 years). RESULTS: Correlation study (Fisher's r to z) showed that UBV correlated negatively with %Bfat (r = -0.61, P < 0.0001), Bfat kg (r = -0.56, P = 0.0001) and marginally with body weight (r = -0.33, P = 0.0403), but did not correlate with FFM kg or H2O L (both r = -0.08, P not significant). When the correlation test was adjusted for weight and age (partial correlation), the negative correlation between UBV and %Bfat persisted (r = -0.54, P < 0.0005; and r = -0.63, P < 0.0001, respectively) and the correlation with FFM kg, adjusted for weight, became positive and significant (r = 0.55, P < 0.0005). CONCLUSIONS: These results, to our knowledge, are the first to be obtained by in vivo evaluation of UBV in relation to body fat and fat-free mass. Body fat, but not fat-free mass, was the main factor affecting UBV. This confirms the deficiency of UBV measurements, considering that obesity is a protective factor for bone mass.

Adipose Tissue↗
PubMed2001

Physical activity and fat-free and fat mass by bioelectrical impedance in 3853 adults.

OBJECTIVE: To determine the effects of regular physical activity on body composition, as measured by bioelectrical impedance analysis (BIA), in a large Caucasian population of healthy subjects between 15 and 64 yr of age, and to observe the cross-sectional changes in body composition with increasing age. DESIGN: Cross-sectional comparison between sedentary and physically active adults (at least 3 h x wk(-1) at moderate or hard intensity level activity) during aging. SUBJECTS: A total of 3853 healthy adults (1036 sedentary and 1019 physically active men, and 1280 sedentary and 518 physically active women) between 15 and 64 yr of age. MEASUREMENTS: Height, weight, body mass index (BMI), and fat-free mass (FFM), fat mass, and % fat mass measured by 50-kHz BIA. RESULTS: Higher weight in older sedentary adults was due to a higher fat mass. In 55- to 64-yr-olds compared with 25- to 34-yr-olds, fat mass was 5.5 kg (P < 0.0001) higher in sedentary and 0.6 kg (P < 0.3) higher in physically active men, and 4.5 kg (P < 0.0001) and 2.0 kg (P < 0.04) higher in sedentary and physically active women, respectively. Physical activity was able to limit fat mass and weight gain in men over 25 yr of age and in women until 54 yr of age. Endurance type physical activity was not associated with increased FFM. For the same BMI, sedentary men and women have < 0.7 kg (P < 0.001) higher fat mass than physically active men and women. CONCLUSION: Therefore, the benefits of physical activity seem to include maintenance or prevention of an increase of BMI that in turn correlates with prevention of a fat mass increase for physically active subjects.

Adipose Tissue↗
PubMed2005

Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma?

PURPOSE: Perinephric and renal sinus fat invasion are classified as pT3a renal cell carcinoma (RCC) according to the 2002 American Joint Committee on Cancer. We investigated the prognostic significance of each of these pathological features using a cohort of pT3a patients. MATERIALS AND METHODS: Between 1970 and 2002, 205 patients without direct adrenal invasion underwent nephrectomy for pT3a clear cell RCC. The associations of fat invasion with death from RCC were evaluated using Cox proportional hazards regression models. RESULTS: Of the 162 patients with perinephric fat invasion and 43 patients with renal sinus fat invasion 95 (59%) and 31 (72%), respectively, died of RCC. Patients with renal sinus fat invasion were 63% more likely to die of RCC compared with those with perinephric fat invasion (RR 1.63, 95% CI 1.09-2.46, p=0.018). In addition, the risk of death persisted in multivariate analysis after adjusting for regional lymph nodes and distant metastases (RR 1.91, 95% CI 1.26-2.89, p=0.002) and after adjusting for the Mayo Clinic SSIGN (stage, size, grade and necrosis) score (RR 1.90, 95% CI 1.25-2.88, p=0.003). CONCLUSIONS: Our results indicate that clear cell tumors invading the renal sinus fat are more aggressive than tumors with perinephric fat involvement. We believe both of these features should be individually assessed during routine pathological examination. External validation is needed before suggesting a change to the TNM staging system.

Adipose Tissue↗
PubMed2002

Developmental changes in opioid peptides and their receptors in Cpe(fat)/Cpe(fat) mice lacking peptide processing enzyme carboxypeptidase E.

Carboxypeptidase E (CPE) is involved in the biosynthesis of a number of neuropeptides including opioid peptides. A point mutation in this gene results in a loss of enzyme activity, decrease in mature neuroendocrine peptides, and development of late onset obesity as seen in Cpe(fat)/Cpe(fat) mice. In this study, we examined the processing of peptides derived from prodynorphin and proenkephalin in various brain regions of these mice during development. At 6 to 8 weeks, an age prior to the onset of obesity, levels of dynorphin peptides are decreased in all brain regions, whereas levels of ir-Met-enkephalin are differentially altered. There is an accumulation of C-terminally extended forms of all three opioid peptides in Cpe(fat)/Cpe(fat) mice, consistent with a lack of CPE activity. Thus, it appears that there is no direct correlation between the level of mature opioid peptides and the development of obesity in these mice. Since altered levels of peptides can influence the opioid receptor system, we examined the functional activity of mu and kappa opioid receptors using [35S]guanosine-5'-O-(gamma-thio)-triphosphate binding assays. We find no differences in kappa receptor activity in Cpe(fat)/Cpe(fat) compared with control littermate mice. In contrast, the mu receptor activity is differentially altered in select regions of Cpe(fat)/Cpe(fat) mice in response to a mu-specific ligand. Taken together, these results suggest that the lack of CPE activity leads to alterations in the level of opioid peptides during development and that changes in peptide levels differentially affect opioid receptor activity in vivo.

Animals↗
PubMed2006

Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk.

BACKGROUND: It is speculated that high saturated fat very low carbohydrate diets (VLCARB) have adverse effects on cardiovascular risk but evidence for this in controlled studies is lacking. The objective of this study was to compare, under isocaloric conditions, the effects of a VLCARB to 2 low saturated fat high carbohydrate diets on body composition and cardiovascular risk. METHODS: Eighty three subjects, 48 +/- 8 y, total cholesterol 5.9 +/- 1.0 mmol/L, BMI 33 +/- 3 kg/m2 were randomly allocated to one of 3 isocaloric weight loss diets (6 MJ) for 8 weeks and on the same diets in energy balance for 4 weeks: Very Low Fat (VLF) (CHO:Fat:Protein; %SF = 70:10:20; 3%), High Unsaturated Fat (HUF) = (50:30:20; 6%), VLCARB (4:61:35; 20%) RESULTS: Percent fat mass loss was not different between diets VLCARB -4.5 +/- 0.5, VLF-4.0 +/- 0.5, HUF -4.4 +/- 0.6 kg). Lean mass loss was 32-31% on VLCARB and VLF compared to HUF (21%) (P < 0.05). LDL-C increased significantly only on VLCARB by 7% (p < 0.001 compared with the other diets) but apoB was unchanged on this diet and HDL-C increased relative to the other 2 diets. Triacylglycerol was lowered by 0.73 +/- 0.12 mmol/L on VLCARB compared to -0.15 +/- 0.07 mmol/L on HUF and -0.06 +/- 0.13 mmol/L on VLF (P < 0.001). Plasma homocysteine increased 6.6% only on VLCARB (P = 0.026). VLCARB lowered fasting insulin 33% compared to a 19% fall on HUF and no change on VLF (P < 0.001). The VLCARB meal also provoked significantly lower post prandial glucose and insulin responses than the VLF and HUF meals. All diets decreased fasting glucose, blood pressure and CRP (P < 0.05). CONCLUSION: Isocaloric VLCARB results in similar fat loss than diets low in saturated fat, but are more effective in improving triacylglycerols, HDL-C, fasting and post prandial glucose and insulin concentrations. VLCARB may be useful in the short-term management of subjects with insulin resistance and hypertriacylglycerolemia.

Journal Article↗
PubMed2004

Central fat mass versus peripheral fat and lean mass: opposite (adverse versus favorable) associations with arterial stiffness? The Amsterdam Growth and Health Longitudinal Study.

Central and peripheral fatness seem to confer opposite (i.e. adverse vs. protective) effects on cardiovascular risk, but how this occurs is not clear. In addition, the role of peripheral lean mass needs to be elucidated. We therefore investigated, in 336 (175 women) 36-yr-old and apparently healthy adults, the relationship between trunk fat, peripheral fat, and peripheral lean mass on the one hand, and estimates of stiffness of three large arteries on the other. Body composition was assessed by dual-energy x-ray absorptiometry. Arterial properties were assessed by ultrasound imaging. We found that 1) trunk fat was positively (i.e. adversely) associated with stiffness of the carotid and femoral arteries, whereas peripheral fat was inversely (i.e. favorably) associated with stiffness of the brachial and the carotido-femoral segment; 2) peripheral lean mass was positively associated with arterial diameter and carotid compliance and inversely associated with stiffness of the carotido-femoral segment; and 3) after adjustment for the other body composition variables, the above-mentioned associations remained, but peripheral fat in addition became, if anything, favorably associated with stiffness of the femoral artery. We conclude that trunk fat is adversely associated with large artery stiffness, whereas some degree of protection is conferred by peripheral fat and lean mass.

Adipose Tissue↗
PubMed1982

The effects of caffeine and exercise on body weight, fat-pad weight, and fat-cell size.

The present investigation was designed to test the ability of caffeine ingestion to enhance the reduction of body fat with exercise. Mature male rats (average weight of 442 g) were assigned to four grouping combinations of the two treatment variables: caffeine ingestion (caf, no caf) and exercise training (ex, sed). Two groups trained by swimming 90 min, 5 d/wk (caf-ex, no caf-ex) while two groups served as untrained controls (caf-sed, no caf-sed). Forty-five minutes prior to swimming, doses of saline only or of caffeine dissolved in saline (5 mg caffeine/kg body weight) were administered to the no caffeine and caffeine groups, respectively. After 9 wk of training, body weight and epididymal and retroperitoneal fat-pad weights were significantly reduced in the caffeine groups and in the exercise groups (P less than 0.05). Epididymal fat-cell size was significantly reduced by caffeine treatment, and exercise training reduced fat-cell diameters in both epididymal and retroperitoneal fat-pads (P less than 0.05). The additional 22% reduction in body weight, 25% reduction in epididymal fat-cell size, and 5 and 6% reductions in epididymal and retroperitoneal fat-pad weights, respectively, in the caf-ex group beyond the no caf-ex group support the hypothesis that fat loss with aerobic exercise can be increased when caffeine is ingested prior to the training sessions.

Adipose Tissue↗
PubMed2000

A new method of quantitative fecal fat microscopy and its correlation with chemically measured fecal fat output.

Fecal fat microscopy using the Sudan stain has suffered from a relative lack of specificity, and results are "qualitative." Therefore, we developed a quantitative fecal fat microscopic method with hopes of improving diagnostic accuracy. One hundred eighty patients with chronic diarrhea collected stools for 1 to 3 days, and fecal fat output was measured by a standard chemical method, and microscopy was performed by the old qualitative and new quantitative methods. There was a highly statistically significant linear correlation between quantitative fecal fat microscopy and chemically measured fecal fat output. The quantitative microscopic method had a sensitivity of 94% and a specificity of 95%; the traditional method had a sensitivity and specificity of 76% and 99%, respectively. Fecal fat Sudan microscopy performed by a dedicated approach to counting and size measurement of fat globules can yield a quantitative result that correlates well with chemically measured fecal fat output and has a high diagnostic accuracy.

Azo Compounds↗
PubMed1994

Influence of ovarian status and regional fat distribution on protein kinase C in rat fat cells.

The effects of ovarian status on insulin- and phorbol 12-myristate 13-acetate (TPA)-stimulated lipogenic responses, phorbol ester-specific binding to protein kinase C (PKC) and immunoblot-quantified beta- and epsilon-PKC isoform levels were compared in female rat fat cells from subcutaneous and deep intra-abdominal (parametrial) fat deposits. In control rats, the cytosolic PKC content per cell was 70% lower in subcutaneous than in parametrial adipocytes. In subcutaneous and parametrial fat cells, the cytosolic PKC contents were reduced by ovariectomy and restored to normal by the administration of ovarian hormones (oestradiol plus progesterone). However, the lipogenic response to TPA was unaltered by ovarian status in both fat deposits, contrasting with the insulin-stimulated lipogenic response. This response increased in parametrial fat cells after ovariectomy and returned to normal after ovarian hormone treatment whereas, in subcutaneous fat cells, the insulin response was either unaltered by ovariectomy or increased by the administration of ovarian hormones. This study shows important site-related differences in fat cell PKC content but also reveals a similar modulation of this PKC by ovarian status, regardless of the anatomical localization of the fat cells. The physiological significance of these findings is discussed.

Adipocytes↗
PubMed2005

Role of soybean oil fat emulsion in the prevention of hepatic xenobiotic transporter mRNA up- and down-regulation induced by overdose of fat-free total parenteral nutrition in infant rats.

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis in human infants. The present study focused on the changes in hepatic xenobiotic transporters associated with overdose of fat-free or fat-containing TPN in infant rats. Three-week-old male Sprague-Dawley rats were divided into three groups: group 1 received an oral diet, group 2 received TPN without fat, and group 3 received TPN with 20% of its calories from fat (soybean oil emulsion). After TPN administration for 4 days, both serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which are indicators of hepatic dysfunction, in group 2 were significantly higher (p<0.001) than those in the other groups, whereas there were no differences between groups 1 and 3 in either serum AST or ALT levels. The serum bilirubin concentration in group 2 was also markedly higher than that in the other groups. Mdr2, Bsep, Mrp2, Mrp6, Oct1, and Oat2 mRNA levels were decreased in group 2 (fat-free TPN) compared with those in group 1 (oral diet), whereas Mdr1b, Mrp1, and Mrp5 mRNA levels were increased. Specifically, the level of Mdr1b mRNA in group 2 was 16 times higher (p<0.001) than that in group 1. On the other hand, the changes in these mRNA expression levels in group 3 (fat-containing TPN) were smaller than those in group 2, and specifically, the expression levels of Mdr1b, Mrp1, Mrp5, Mrp6, and Oat2 mRNA in group 3 were not significantly different from those in group 1. The results of the present study indicate that including fat in the TPN regimen is very important in preventing the mRNA up- and down-regulation of xenobiotic transporters, which is considered to be the main factor responsible for the abnormal hepatic changes such as cholestasis associated with the excessive administration of fat-free TPN.

ATP-Binding Cassette Transporters↗
PubMed1999

Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes.

OBJECTIVE: To examine the effects of a thiazolidinedione (600 mg troglitazone) insulin-sensitizing treatment on total body fat measured by underwater weighing, on intra- and extra-abdominal fat mass using magnetic resonance imaging (MRI), and on anthropometric measures. RESEARCH DESIGN AND METHODS: Type 2 diabetic outpatients were studied in a double-blind randomized trial carried out at Glasgow Royal Infirmary, Scotland. RESULTS: Groups who received troglitazone (8 men, 3 women) and placebo (8 men, 2 women) were well matched for age, BMI, total body fat percentage by underwater weighing, and intra-abdominal fat (kilograms) by MRI. After 12 weeks, body weight changes in the troglitazone group (mean +0.66 kg [95% CI -0.71 to 2.04], P = 0.31) and the placebo group (mean +0.25 kg [-0.64 to 1.13], P = 0.55) were not statistically different. Changes in total body fat with troglitazone (mean +1.02% body wt [-1.13 to 3.17], P = 0.32) and placebo (mean -0.54% body wt [-1.68 to 0.59], P = 0.31) were not significantly different. There was, however, a decrease in intra-abdominal fat mass in the troglitazone-treated group (mean -0.47 kg [-0.79 to -0.13], P = 0.01), and this was significantly different (P = 0.03) from placebo treatment (mean -0.41 kg [-0.77 to -0.05]). CONCLUSIONS: Treatment with the thiazolidinedione troglitazone in human patients with type 2 diabetes decreases intra-abdominal fat mass but does not affect total body fat or weight. This potentially valuable effect points to a differential action on insulin sensitivity in different adipose tissue depots.

Abdomen↗
PubMed1997

Effect of fat content of colostrum on voluntary colostrum intake and fat utilization in newborn pigs.

The effects of colostral fat level on voluntary colostrum and ME intake were determined in 25 newborn pigs during the first postnatal day. Within a litter, five pigs were obtained before nursing and allotted on the basis of initial body weight (BW) at 2 h of age to one of the five treatments: killed or ad libitum bottle-fed sow colostrum containing 2.5, 5.0, 7.5, or 10.0% of total fat. A total of 24 feedings was provided at 60-min intervals, and pigs were killed 1 h after the final feeding. Total colostrum intake averaged 584.8 +/- 42 g (i.e., 436 g/kg of average BW) with the first two feedings accounting for 19.8% of the total consumption. Colostrum intake decreased linearly (P < .08) by 5.9 g/kg of average BW per 1% increase in the level of fat. However, GE and ME intake increased linearly (P < .01) by 7.65 and 4.09 kcal/kg average BW per 1.0 g/kg of average BW increase in fat intake, respectively. Adipose tissue lipoprotein lipase increased (P < .01) during the first postnatal day. Carcass fat deposition and fat oxidation increased linearly (P < .01) by .36 and .20 g/kg of average BW per 1.0 g/kg of average BW increase in fat intake, respectively. We suggest that increasing the fat content in colostrum has little effect on voluntary colostrum intake, and the practice may be an efficient method for improving the energy supply to newborn pigs.

Adipose Tissue↗