Biomedical subjects

C A Drevon

Publications and source records attributed to C A Drevon.

At least 19 recordsLinked to original sources

PubMed2007

Cell-based multiwell assays for the detection of substrate accumulation and oxidation.

We describe multiwell assays for detecting the accumulation as well as the subsequent oxidation of (14)C-labeled substrates in cultured cells. Accumulation is monitored in real time by an established scintillation proximity assay in which the scintillator is embedded in the plate base primarily detecting cell-associated radiolabel. The substrate oxidation assay is a novel variant of previously described experimental approaches aimed at trapping (14)CO(2) produced by isolated enzymes, organelles, or intact cells. This method uses a standard 96-well tissue culture plate and, on top, an inverted filter plate immersed with NaOH that are clamped into a sandwich sealed with a silicon gasket to obtain gas-tight compartments. (14)CO(2) is captured in the filter and quantified by conventional scintillation. We demonstrate both the accumulation and subsequent oxidation of (14)C-labeled substrates in cultured human myotubes, adipocytes, and hepatocytes. Both methods are adaptable for compound screening; at the same time, these protocols provide easy-to-use and time- saving methods for in vitro studies of cellular fuel handling.

Adipocytes↗

PubMed2006

Fat-soluble vitamins in breast-fed preterm and term infants.

OBJECTIVE: To examine the supply and status of fat-soluble vitamins in very low birth weight (VLBW) infants compared to a reference group of normal birth weight (NBW) infants. DESIGN: A longitudinal study of VLBW infants in the early neonatal period. Blood samples were drawn at 1 week of age and at discharge from hospital. Plasma was analyzed for the fat-soluble vitamins: retinol, 25-OH-vitamin D, alpha-tocopherol and phylloquinone (vitamin K(1)) using high-performance liquid chromatography. SUBJECTS: A total of 40 VLBW infants were included in the study. A reference group of 33 NBW infants was randomly selected from one of our previous studies. RESULTS: The VLBW infants received fortified human milk, and daily oral vitamin supplement (Multibionta). In VLBW infants, plasma retinol concentrations decreased and plasma 25-OH-vitamin D increased during the study period. VLBW infants had significantly lower plasma retinol (0.3 vs 0.7 mu M) and higher plasma 25-OH-vitamin D (166 vs 25 nM) at discharge compared to NBW infants. Plasma phylloquinone concentration in VLBW infants was very high (53 ng/ml) at one week of age, especially in the youngest infants (192 ng/ml), but decreased rapidly during the study period resulting in low/normal plasma concentrations (0.9 ng/ml) at discharge. CONCLUSIONS: We observed alterations in plasma concentration of retinol and 25-OH-vitamin D in VLBW infants in the early neonatal period, resulting in marked differences between VLBW at discharge and NBW. Further trials are needed to evaluate whether changes in vitamin supplementation may improve clinical outcome in VLBW infants.

Antioxidants↗

PubMed2006

Dietary intake and nutritional indicators are transiently compromised during radiotherapy for rectal cancer.

OBJECTIVE: Patients with rectal cancer receive curative radiotherapy towards the pelvis for 5 weeks. Little is known about the impact of radiotherapy on dietary intake and nutritional status. The objective was to examine whether curative radiotherapy for rectal cancer promoted altered intake of energy and nutrients, and change in nutritional indicators. DESIGN: Prospective study. SETTING: Department of Oncology in a tertiary care hospital. SUBJECTS: A total of 31 consecutive patients receiving radiotherapy for rectal cancer (50 Gray). INTERVENTIONS: A 7-day food intake registration, body weight, upper arm circumference, and analyses of blood samples were performed at the start and the end of radiotherapy, and at follow-up 4-6 weeks and 1 year after the end of radiotherapy. RESULTS: At the end of 5 weeks of radiotherapy, the mean daily energy intake was reduced by 15% from 8.9 to 7.6 MJ as compared with baseline (P = 0.002), and the intake of several nutrients was reduced (P < 0.01). The percentages of energy derived from fat, protein, and carbohydrates did not change, nor did the nutrient density. A transient body weight reduction of < 1 kg was observed (P = 0.009). Serum concentrations of vitamin A and 25-OH vitamin D did not change during radiotherapy. The daily intake of energy and nutrients, and body weight, had increased towards pretreatment values 4-6 weeks after radiotherapy. CONCLUSIONS: Radiotherapy for rectal cancer caused a transient reduction in energy intake and nutritional indicators. The nutritional quality of the diet was unchanged during radiotherapy.

Aged↗

PubMed2005

Evaluation of the odd fatty acids 15:0 and 17:0 in serum and adipose tissue as markers of intake of milk and dairy fat.

BACKGROUND: There is a need for biomarkers of dietary saturated fatty acids, because several diseases have been related to intake of these fatty acids. OBJECTIVE: To examine the relation between intake of dairy fat and the proportion of pentadecanoic (15:0) and heptadecanoic (17:0) acid in serum and adipose tissue. DESIGN: Healthy men aged 21-55 y provided serum (n = 110) and adipose tissue samples (n = 107) and completed both 14 days weighed records (WR) and a 180-item food frequency questionnaire (FFQ). The proportions of 15:0 and 17:0 acid in serum and adipose tissue as measured by gas liquid chromatography were evaluated as biomarkers for fat intake from dairy products using Pearsons correlation coefficient and the method of triads. RESULTS: The strongest correlation coefficients were observed between total intake of dairy fat estimated from WR and relative content of 15:0 in adipose tissue (0.52, 95% CI: 0.37, 0.65) and total serum (0.43, 95% CI 0.26, 0.57). A consistent inverse association was observed between the intake of milk fat and relative serum content of 17:0. The validity coefficients observed for the intake of dairy fat estimated from weighed records, the 180-item FFQ and by the relative content of 15:0 in serum and adipose tissue were 0.94 (95% CI: 0.68, 1.00), 0.50 (95% CI: 0.29, 0.67), 0.49 (95% CI: 0.32, 0.67) and 0.56 (95% CI: 0.28, 0.82), respectively. CONCLUSION: Relative content of 15:0 in serum and adipose tissue may be a useful biomarker for the intake of total dairy fat, whereas FFQs and WRs may provide better estimates of the intake of fat from milk.

Adipose Tissue↗

PubMed2004

Six carotenoids in plasma used to assess recommended intake of fruits and vegetables in a controlled feeding study.

BACKGROUND: There is a need for objective and universally applicable biomarkers for the intake of foods believed to affect human health. OBJECTIVE: The purpose of this feeding study was to test whether plasma concentrations of carotenoids could be used to distinguish recommended consumption of mixed fruits and vegetables (five a day) from the current national intake of fruits and vegetables (two a day). DESIGN: A strict crossover design was chosen to correct for observed interindividual variations in carotenoid response. A total of 40 healthy subjects were included in the study. After 1 week run-in period with no fruits and vegetables in the diet, one group was given two portions (300 g) of fruits and vegetables daily, while another group was given five portions (750 g) for 14 days. Following a 2 week wash-out period and 1 week run-in, the regimens were switched between the groups. Fruits and vegetables were combined to match a typical Norwegian diet. RESULTS: Enhanced intake from two to five portions of mixed fruits and vegetables increased plasma concentrations of alpha-carotene (P=0.033) and lutein (P=0.051) in a crossover analysis. Analysis of data in the parallel part of the study revealed differences between the high and low intake for plasma concentrations of alpha-carotene (P=0.013) and beta-carotene (P=0.016). A trend was also evident for plasma concentrations of lycopene (P=0.057) and lutein (P=0.076) in the parallel analysis. No effect of high vs low intake of fruits and vegetables was observed for plasma concentrations of beta-cryptoxanthin, zeaxanthin, cholesterol and triacylglycerols. CONCLUSION: The study indicates that plasma concentration of alpha-carotene, beta-carotene and lutein may be used to assess changes of fruit and vegetable intake corresponding to an increase from the present national intake in Norway to the recommended amount of five portions of fruits and vegetables daily. SPONSORSHIP: Norwegian Research Council, National Nutrition Council, Throne Holst Foundation for Nutrition Research and Freia Chokoladefabriks Medisinske Fond.

Adult↗

PubMed2003

The hypotriglyceridemic effect of dietary n-3 FA is associated with increased beta-oxidation and reduced leptin expression.

To study the mechanisms responsible for the hypotriglyceridemic effect of marine oils, we monitored the effects of high dietary intake of n-3 PUFA on hepatic and muscular beta-oxidation, plasma leptin concentration, leptin receptor gene expression, and in vivo insulin action. Two groups of male Wistar rats were fed either a high-fat diet [28% (w/w) of saturated fat] or a high-fat diet containing 10% n-3 PUFA and 18% saturated fat for 3 wk. The hypotriglyceridemic effect of n-3 PUFA was accompanied by increased hepatic oxidation of palmitoyl-CoA (125%, P < 0.005) and palmitoyl-L-carnitine (480%, P < 0.005). These findings were corroborated by raised carnitine palmitoyltransferase-2 activity (154%, P < 0.001) and mRNA levels (91%, P < 0.01) as well as by simultaneous elevation of hepatic peroxisomal acyl-CoA oxidase activity (144%, P < 0.01) and mRNA content (82%, P < 0.05). In contrast, hepatic carnitine palmitoyltransferase-1 activity remained unchanged despite a twofold increased mRNA level after n-3 PUFA feeding. Skeletal muscle FA oxidation was less affected by dietary n-3 PUFA, and the stimulatory effect was found only in peroxisomes. Dietary intake of n-3 PUFA was followed by increased acyl-CoA oxidase activity (48%, P < 0.05) and mRNA level (83%, P < 0.05) in skeletal muscle. The increased FA oxidation after n-3 PUFA supplementation of the high-fat diet was accompanied by lower plasma leptin concentration (-38%, P < 0.05) and leptin mRNA expression (-66%, P < 0.05) in retroperitoneal adipose tissue, and elevated hepatic mRNA level for the leptin receptor Ob-Ra (140%, P < 0.05). Supplementation of the high-fat diet with n-3 PUFA enhanced in vivo insulin sensitivity, as shown by normalization of the glucose infusion rate during euglycemic hyperinsulinemic clamp. Our results indicate that the hypotriglyceridemic effect of dietary n-3 PUFA is associated with stimulation of FA oxidation in the liver and to a smaller extent in skeletal muscle. This may ameliorate dyslipidemia, tissue lipid accumulation, and insulin action, in spite of decreased plasma leptin level and leptin mRNA in adipose tissue.

Animals↗

PubMed2002

Altered plasma concentrations of leptin, transforming growth factor-beta(1) and plasminogen activator inhibitor type 2 at 18 weeks of gestation in women destined to develop pre-eclampsia. Circulating markers of disturbed placentation?

BACKGROUND: In many pre-eclamptic women the placentation process seems to be disturbed. Our objective was to investigate if disturbed placentation in pre-eclamptic women may be recognized in early second trimester as altered plasma levels of factors involved in the formation of the uteroplacental unit. METHODS: In a prospective study of 2190 pregnant women we compared plasma leptin, transforming growth factor-beta(1) (TGF-beta(1)) and plasminogen activator inhibitor type 2 (PAI-2) concentrations at 18 weeks' gestation in 71 women with subsequent pre-eclampsia and 71 controls matched for age, parity and first trimester body mass index. RESULTS: Leptin and TGF-beta(1) concentrations were lower and PAI-2 concentration higher in women destined to develop pre-eclampsia relative to controls (leptin: median (25-75 percentiles): 19.0 (14.5-29.0) vs 25.0 (16.0-35.0) ng/ml (p =0.03), TGF-beta(1): 3.2 (2.0-6.1) vs 5.3 (3.8-7.1) ng/ml (P=0.01) and PAI-2: 78.8 (65.1-118.1) vs 67.6 (61.6-79.6) ng/ml (P=0.002)). OR (95 per cent CI) for pre-eclampsia for women in the upper quartile compared to women in the lower quartile were: leptin: 0.2 (0.03-0.7), TGF-beta(1): 0.2 (0.08-0.7) and PAI-2: 3.1 (1.2-8.2). CONCLUSIONS: Altered plasma concentrations levels of factors involved in the process of placentation in women destined to develop pre-eclampsia, indicate that disturbed formation of the uteroplacental unit is reflected in the maternal circulation before 20 weeks' gestation.

Adult↗

PubMed2002

An increase in peroxisomal fatty acid oxidation is not sufficient to prevent tissue lipid accumulation in hHTg rats.

We observed earlier that increased skeletal muscle lipid content in the hereditary hypertriglyceridemic (hHTg) rat is accompanied by a decline in plasma leptin. Leptin has recently been shown to enhance peripheral insulin sensitivity by decreasing the tissue triglyceride accumulation, possibly through regulation of fatty acid oxidation and lipogenesis. Thus, to test the hypothesis that insulin resistance and increased skeletal muscle lipid accumulation in hHTg rats are due to a defect in lipid catabolism, we measured mitochondrial and peroxisomal fatty acid oxidation and malonyl-CoA and acetyl-CoA carboxylase-2 content in skeletal muscles of these animals. In addition, we investigated possible molecular mechanisms responsible for the lower leptin levels in hHTg rats by measuring leptin and leptin-receptor (Ob-Ra) mRNA levels. We found the following: (1) in spite of a higher skeletal muscle malonyl-CoA content and an increased sensitivity of carnitine palmitoyltransferase-1 to malonyl-CoA, carnitine palmitoyltransferase-1 activity in muscle of hHTg rats was normal; (2) increased peroxisomal fatty acid oxidation did not seem to be sufficient to prevent the tissue lipid accumulation in these animals; (3) both lower leptin production by white adipose tissue and increased leptin uptake seem to be responsible for lower circulating leptin levels and therefore lower fatty acid catabolism.

Animals↗

PubMed2001

Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes.

Expression of the gene encoding resistin, a low molecular weight protein secreted from adipose tissue postulated to link obesity and type II diabetes, was examined in 3T3-L1 adipocytes. Resistin mRNA was detected in 3T3-L1 cells by day 3 following induction of differentiation into adipocytes; by day 4 the level of resistin mRNA peaked and remained high. The PPARgamma activators, rosiglitazone or darglitazone, reduced the level of resistin mRNA. Dexamethasone upregulated resistin mRNA level, but no effect was observed with the beta(3)-adrenoceptor agonist, BRL 37344. A substantial reduction in resistin mRNA level was observed with insulin, which induced decreases at physiological concentrations. Insulin may be a major inhibitor of resistin production, and this does not support a role for resistin in insulin resistance.

3T3 Cells↗

PubMed2001

Necrosis and apoptosis in lymphoma cell lines exposed to eicosapentaenoic acid and antioxidants.

The present study is focused on the role of oxidative stress in the induction of either necrosis or apoptosis by eicosapentaenoic acid (EPA) in the lymphoma cell lines Raji and Ramos, respectively. To investigate the different death modes induced by EPA, we assessed the importance of some antioxidants and reactive oxygen species in the two cell lines. We observed that different antioxidants counteracted the necrotic effect of EPA on Raji cells to a different extent, and that vitamin E counteracted EPA-induced accumulation of superoxide anion in this cell line. On the contrary, no effects of antioxidants were observed on development of apoptosis induced by EPA in Ramos cells, and vitamin E did not counteract EPA-induced accumulation of superoxide anions in Ramos cells. Moreover, apoptosis was partly inhibited by transcription inhibitors (actinomycin D) and protein synthesis inhibitors (cycloheximide), suggesting dependency upon new protein synthesis prior to apoptosis. Kinase inhibitors (staurosporin and calphostin C) did not alter the EPA-induced apoptosis. The observed cellular accumulation of superoxide anion following EPA incubation may be important for induction of necrosis in Raji cells. In contrast, none of the other investigated parameters indicated a role of oxidative stress promoted by EPA in the induction of apoptosis in Ramos cells.

Antioxidants↗

PubMed2001

High intake of energy, sucrose, and polyunsaturated fatty acids is associated with increased risk of preeclampsia.

OBJECTIVE: Preeclampsia is associated with high body mass index, insulin resistance, and hypertriglyceridemia. Our objective was to investigate prospectively whether diet in the first half of pregnancy is associated with the risk for preeclampsia. STUDY DESIGN: This prospective, population-based, cohort study of pregnant women investigated dietary intake early in the second trimester with a quantitative food frequency questionnaire. RESULTS: The questionnaire was completed by 3133 women (83%). Preeclampsia developed in 85 women. Adjusted odds ratio (95% CI) for preeclampsia was 3.7 (1.5-8.9) for energy intake of >3350 kcal/d compared with < or =2000 kcal/d. Adjusted odds ratio (95% CI) for preeclampsia was 3.6 (1.3-9.8) for sucrose intake (percent of total energy) of >25% compared with < or =8.5% and 2.6 (1.3-5.4) for polyunsaturated fatty acids intake (percent of total energy) of >7.5% compared with < or =5.2%. Other energy-providing nutrients were not associated with the risk for preeclampsia. CONCLUSION: The current study suggests that high intakes of energy, sucrose, and polyunsaturated fatty acids independently increase the risk for preeclampsia.

Adult↗

PubMed2001

Effect of long-term changes in diet and exercise on plasma leptin concentrations.

BACKGROUND: Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body, little information is available on the long-term effects on leptin concentrations of changes in diet and exercise. OBJECTIVE: We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure, alone or in combination, affect plasma leptin concentrations. DESIGN: In a randomized, 2 x 2 factorial trial, 186 men with metabolic syndrome were divided into 4 groups: diet, exercise, a combination of diet and exercise, and control. Data on dietary intake, physical fitness, and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period. RESULTS: Plasma leptin concentrations, body mass index, and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity. By adjusting for either body mass index or fat mass, we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions. There was no interaction between the interventions, suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations. CONCLUSION: Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass.

Adipose Tissue↗

PubMed2001

Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.

The adipose hormone leptin and its receptor are important for regulation of food intake and energy metabolism. Leptin also is involved in the growth of different tissues. In this study, we show the expression of leptin in primary cultures of normal human osteoblasts (hOBs) as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry. Release of leptin into the medium also was found. Leptin was not detected in commercially available hOBs (NHOst) or in three different human monoclonal osteosarcoma cell lines. Leptin expression was observed in OBs in the mineralization and/or the osteocyte transition period but not during the matrix maturation period. Furthermore, hOBs and osteosarcoma cell lines expressed the long signal-transducing form of the leptin receptor (OB-Rb) as shown by RT-PCR. We observed no significant changes in leptin or OB-Rb genes in hOBs after incubation with recombinant leptin, indicating no autoregulation of the leptin expression. Incubation of both hOBs entering the mineralization phase and osteosarcoma cell lines with recombinant leptin markedly increased the number of mineralized nodules as shown by alizarin S staining. These findings indicate that leptin may be of importance for osteoblastic cell growth and bone mineralization.

3T3 Cells↗

PubMed2001

Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women.

OBJECTIVE: There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids (PUFAs) during pregnancy may increase birth weight and gestational length. In addition, n-3 long-chain PUFAs may be important for the neurobiological development of the infants. High levels of docosahexaenoic acid (DHA, 22:6 n-3) are found in the gray matter of the cerebral cortex and in the retina, and it seems as if the availability of long-chain PUFAs may be limiting cerebral development. The fetus and the newborn are dependent on a high supply from their mothers, either via the placenta or via breast milk. We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight, gestational length, and infant development. DESIGN: We performed a double-blind, randomized study recruiting 590 pregnant, healthy, nulli- or primiparous women (19-35 years old) in weeks 17 to 19 of pregnancy. The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery. MAIN OUTCOME MEASURES: Primary outcomes were gestational length and birth weight. Electroencephalography (EEG) was done on the second day of life and at 3 months of age. Novelty preference (Fagan test) was used as an indicator of cognitive function at 6 and 9 months of age. The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured, and dietary assessments were performed, both on the mothers during pregnancy and on the infants at 3 months of age. The growth of the infants was followed up to 1 year of age. RESULTS: Three hundred forty-one mothers took part in the study until delivery. There were no significant differences in maternal body mass index before pregnancy and at birth, or parity between the 2 groups. Smoking habits and parental education were also similar in the 2 groups. The mean age of the mothers receiving cod liver oil was, by chance, 1 year higher than the age of the mothers receiving corn oil (28.6 [3.4] vs 27.6 [3.2] years). The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar, except for the supplementation. There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group (279.6 [9.2] vs 279.2 [9.3] days; 3609 [493] vs 3618 [527] g, respectively). Birth length, head circumference, and placental weight were also similar in the 2 groups. The concentrations of the n-3 fatty acids eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3), and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group (10.8 [7.6] vs 2.5 [1.8] microg/mL, 5.0 [2.6] vs 2.9 [1.3] microg/mL, 55.8 [20.6] vs 45.3 [12.8] microg/mL, respectively). Neonates with high concentration of DHA in umbilical plasma phospholipids (upper quartile) had longer gestational length than neonates with low concentration (lower quartile; 282.5 [8.5] vs 275.4 [9.3] days). No differences in EEG scores or Fagan scores were found, but neonates with mature EEG (N = 70) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG (N = 51) on the second day of life. Dietary information from 251 infants at 3 months of age was collected and 85% of these infants were exclusively breastfed, in addition to 12% who were partly breastfed. The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil. There were no significant differences in infant growth during the first year of life between the 2 groups. CONCLUSIONS: This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome, cognitive development, or growth, as compared with supplementation with n-6 fatty acids. However, it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn.

Abnormalities, Multiple↗

PubMed2001

Pharmacological interference with transcriptional control of osteoblasts: a possible role for leptin and fatty acids in maintaining bone strength and body lean mass.

Osteoblasts pass through a sequence of events controlled by hormones and transcriptional factors ensuring proper development of phenotype and functional properties until the osteoblast enter the osteocyte phenotype and/or undergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins and mineralize it until they turn into osteocytes believed to constitute a mechanosensor mesh giving feed-back to the osteoblast to initiate bone modeling or remodeling necessary for the making or remaking of proper bone architecture and strength. It appears that several factors common to osteoblast and adipocyte differentiation determine their entry into different functional stages. Such factors are insulin, growth hormone (GH), insulin-like growth factor type I (IGF-I), transforming growth factor beta (TGFbeta), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), cytokines (e.g. interleukins, interferon and tumor necrosis factor alpha (TNF alpha), bone morphogenetic proteins (BMPs), glucocorticoids, retinoic acid (RA), prostaglandins and cAMP-elevating hormones. The focus of this article is to review the effects of leptin on bone cells and bone turnover, the peroxisome proliferator-activated receptors (PPARs) in the regulation of bone and fat cell differentiation, hormones and fatty acids on the orchestration of osteoblast and adipocyte derived regulatory signals, and mechanostimulation of bone on the mechanisms by which the above mentioned factors modulate osteoblast and adipocyte function. The hypothesis or concept is that prescription of a certain treatment regimen to correct bone turnover, without attempting to assess how hormonal homeostasis, nutritional factors and physical exercise may interact locally, will remain far from optimal, and may even prove detrimental to the patient's health condition.

Adipocytes↗

PubMed2001

Smoking related to plasma leptin concentration in pregnant women and their newborn infants.

UNLABELLED: Leptin, a hormone produced in adipose tissue and placenta, is potentially important in relation to energy metabolism and growth. We investigated the effect of cigarette smoking on maternal plasma leptin concentration during pregnancy, and on plasma leptin concentration and weight among infants up to 13 wk of age. Plasma leptin concentration was measured in women in week 18 (n = 203) and week 35 (n = 164) of pregnancy, while cotinine (nicotine metabolite) was measured in plasma sampled from mothers in week 35 of pregnancy (n = 159). Leptin concentration was also measured in plasma from the umbilical cord (n = 133) and from 4-wk-old (n = 129) and 13-wk-old (n = 130) infants. There was no difference in plasma leptin concentration between smoking and non-smoking mothers at 18 wk and at 35 wk of pregnancy. Plasma cotinine concentration was higher in smoking than in non-smoking mothers, and a negative correlation between plasma cotinine and leptin concentrations was found. The leptin concentrations in umbilical cord plasma were similar, although the birthweights of newborns from smoking mothers were significantly lower than those from non-smoking mothers. The plasma leptin concentrations were similar between the two groups also at 4 wk of age. At 13 wk of age, infants of smoking mothers had significantly higher plasma leptin concentrations than infants of non-smoking mothers. CONCLUSION: Our results indicate that a lower birthweight of neonates among smoking mothers is not due to altered plasma leptin concentration.

Adult↗

PubMed2001

Reduction of leptin gene expression by dietary polyunsaturated fatty acids.

Supplementation with n-3 polyunsaturated fatty acids (PUFA) for 6 weeks did not alter plasma leptin concentrations in male smokers. Changes in dietary intake of saturated fatty acids (FA) correlated positively, whereas changes in the intake of PUFA correlated negatively to changes in plasma leptin levels. A 3-week n-3 PUFA-enriched diet, as compared with a 3-week lard-enriched diet, induced lower plasma leptin concentration and reduced leptin mRNA expression in rat epididymal adipose tissue. In the human trophoblast cell line (BeWo), n-3 PUFA had a dose- and time-dependent effect on leptin expression. One mM of eicosapentaenoic acid or docosahexaenoic acid (DHA) reduced leptin expression by 71% and 78%, respectively, as compared with control, after 72 h. There was no effect on expression of the signal transducing form of the leptin receptor. In BeWo cells transfected with the human leptin promoter, we found that n-3 PUFA reduced leptin promoter activity; in contrast saturated and monounsaturated FA had no effect on leptin promoter activity. The transcription factors peroxysomal proliferator activated receptor gamma and sterol regulatory element binding protein-1 mRNAs were reduced after incubation with n-3 PUFA, whereas the expression of CCAAT/enhancer binding protein alpha was unchanged. DHA-reduced leptin expression was abolished in BeWo cells grown in cholesterol-free medium. In conclusion, n-3 FA decreased leptin gene expression both in vivo and in vitro. The direct effects of PUFA on leptin promoter activity indicate a specific regulatory action of FA on leptin expression.

Adipose Tissue↗

PubMed2000

One or more labile proteins regulate the stability of chimeric mRNAs containing the 3'-untranslated region of cholesterol-7alpha -hydroxylase mRNA.

Multiple AUUUA elements similar to those that regulate the degradation of several different mRNAs are conserved in the 3'-untranslated region (3'-UTR) of cholesterol-7alpha-hydroxylase (CYP7A1) mRNAs from several species. We examined if stabilization of mRNA decay could account for the >20-fold increase in the expression of CYP7A1 mRNA without a detectable change in transcription following dexamethasone treatment of rat hepatoma cells (L35 cells). Following RNA polymerase II-dependent transcription block or protein synthesis block, the decay of CYP7A1 mRNA displayed a short half-life ( approximately 30 min). Control experiments showed that in cells pre-treated with a RNA polymerase II inhibitor, dexamethasone had no detectable effect on CYP7A1 mRNA decay. Stable expression of luciferase reporter mRNAs in L35 cells showed that the CYP7A1 3'-UTR was required to observe a dexamethasone induction. To examine the hypothesis that a labile protein is required for dexamethasone-induced mRNA stabilization, cells were stably transfected with a tetracycline-repressible promoter that drives the expression of a green fluorescent protein analogue (ECFP) with or without the 3'-UTR of CYP7A1. Cells expressing ECFP with the 3'-UTR of CYP7A1 displayed a 3-fold dexamethasone induction of ECFP mRNA, whereas cells expressing ECFP without the 3'-UTR did not. Moreover, specific block of the transcription of ECFP containing the 3'-UTR by adding the tetracycline analogue doxycycline clearly displayed dexamethasone-induced stabilization of mRNA decay. These data provide compelling evidence that a putative labile protein and the 3'-UTR of CYP7A1 act together to decrease the rate of CYP7A1 mRNA degradation.

3' Untranslated Regions↗