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Biomedical subjects

C Couet

Publications and source records attributed to C Couet.

At least 37 records · Page 2Linked to original sources

Linoleic acid uptake by isolated enterocytes: influence of alpha-linolenic acid on absorption.

In a previous study we showed that intestinal uptake of alpha-linolenic acid (18:3n-3) was carrier-mediated and we suggested that a plasma membrane fatty acid protein was involved in the transport of long-chain fatty acids. To further test this hypothesis, the mechanism of linoleic acid (18:2n-6) uptake by isolated intestinal cells was examined using a rapid filtration method and 20 mM sodium taurocholate as solubilizing agent. Under these experimental conditions transport of [1-14C]linoleic acid monomers in the concentration range of 2 to 2220 nM was saturable with a Vm of 5.1 +/- 0.6 nmol/mg protein/min and a Km of 183 +/- 7 nM. Experiments carried out in the presence of metabolic inhibitors, such as 2,4-dinitrophenol and antimycin A, suggested that an active, carrier-mediated mechanism was involved in the intestinal uptake of this essential fatty acid. The addition of excess unlabeled linoleic acid to the incubation medium led to a 89% decrease in the uptake of [1-14C]linoleic acid, while D-glucose did not compete for transport into the cell. Other long-chain polyunsaturated fatty acids added to the incubation mixture inhibited linoleic acid uptake by more than 80%. The presence of alpha-linolenic acid (18:3n-3) in the incubation medium caused the competitive inhibition (Ki = 353 nM) of linoleic acid uptake. The data are compatible with the hypothesis that intestinal uptake of both linoleic, and alpha-linolenic acid is mediated by a membrane carrier common to long-chain fatty acids.

Animals↗

alpha-Linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer.

The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initially localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of alpha-linolenic acid (18:3n-3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3n-3 were single factors significantly associated with an increased risk of metastasis. A Cox proportional hazard regression model was used to identify prognostic factors. Low 18:3n-3 level and large tumour size were the two factors predictive of metastases. These results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo. Further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.

Adipose Tissue↗

Glucose oxidation after a peritoneal and an oral glucose load in dialyzed patients.

Glucose oxidation and thermogenesis were studied after a peritoneal (P) and an oral (O) glucose load in nine chronically uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 24.4 +/- 5.8 months. The O load (50 g) given was equivalent to the amount of glucose absorbed over six hours through the peritoneum of the subjects (51.7 +/- 3.3 g). Glucose oxidation and energy expenditure were obtained using indirect calorimetry in basal state and over the six hours following the glucose load. Glucose oxidation rate was higher from 60 to 180 minutes after O than after P (P < 0.05), with peak values of 3.85 +/- 0.28 mg.kg-1.min-1 and 2.80 +/- 0.17 mg.kg-1.min-1 respectively (P < 0.05). Cumulated glucose oxidation over six hours was 53.6 +/- 0.6 versus 47.0 +/- 3.4 g after O and P respectively (NS). Glucose-induced thermogenesis was 8.7 +/- 2.9% versus 5 +/- 1.9% after O and P, respectively (NS). The route of administration of glucose induces different kinetics of the glucose oxidation rate, but a similar amount of glucose absorbed either by the peritoneum or by the gut contributes in a similar extent to glucose and energy balance.

Absorption↗

Effect of calcium and mineral waters on oleic-acid uptake by isolated hamster enterocytes.

The effect of calcium upon the uptake of oleic acid solubilized with 10 mM taurocholate was investigated using an in vitro model of isolated enterocytes. The addition of Ca2+ to the incubation medium (Hanks' medium) led to a decrease in oleic-acid uptake. This uptake inhibition was dependent on both the amount of Ca2+ and the fatty-acid concentration, since the inhibitory effect was significant for 10 microM but not 100 microM oleic acid. The determination of the monomeric activity of oleic acid indicated that the decrease in fatty-acid uptake was not linked to the formation of insoluble calcium soaps. The replacement of Hank's medium by several mineral waters containing between 0.3 and 11.7 mM Ca2+ significantly reduced the uptake of both 10 and 100 microM oleic-acid. The ionic composition of these waters was correlated with the decrease of initial rate of oleic acid uptake, but Ca2+ and other ions could interfere by synergetic effects with the fatty-acid-absorption mechanism. It is concluded that the ion-induced inhibition of oleic-acid uptake is not due to the formation of insoluble soaps but rather to a direct effect on the fatty-acid transport in membranes. Whether the fatty-acid binding protein in the plasma membrane is involved in the effect of Ca2+ on fatty-acid transport remains to be established.

Animals↗

Anthropometric values in an elderly French population.

We compared anthropometric indices in samples of elderly people aged 65 years and over living in two French areas. The samples were divided into four age-groups (65-69, 70-74, 75-79 and over 80 years). We observed interregional differences in women aged 65-69 years and in men aged 65-74 years. Weight and anthropometric variables related to body fat percentage and to muscle mass showed a decline with age as already reported by others. We established anthropometric percentile values according to sex in pooled subjects when no integrated difference was found. The 50th percentile of arm circumference, muscle arm circumference and triceps skinfold was higher, and the 50th percentile of body mass index was lower than the one reported for the same indices from an elderly Welsh population. Our results show that an interregional difference in anthropometric indices exists in the elderly. The differences which are observed between our results and those reported from a British population emphasize the importance of establishing local values for the elderly population.

Aged↗

Plasma lipids and alcohol consumption in alcoholic men: effect of withdrawal.

This study examines the effect of alcohol withdrawal on plasma lipids and particularly on HDL-cholesterol subfractions, in 18 middle-aged, clinically healthy but chronically drinking men, institutionalized for withdrawal therapy. Plasma lipids, total HDL and HDL3-cholesterol, Apo A-I and Apo B were assayed before and after 30-86 days of abstinence. A 38% decrease in mean total HDL-cholesterol levels was observed after withdrawal therapy (P = 0.0002), and this was due mainly to a drop in HDL3-cholesterol concentrations (-43%, P = 0.0002). The decrease in HDL2-cholesterol concentrations was also significant (-21%, P < 0.005) but less marked. These results were not dependent on quantities of alcohol ingested before therapy, on duration of hospitalization and on changes in dietary fat intake or smoking habits. Apo A-I levels decreased (-39%, P = 0.0002) and the magnitude of the decrease after alcohol withdrawal was positively related to the duration of hospitalization. Apo B levels increased (+24%, P < 0.005). Among the anthropometric parameters, arm muscle area was significantly higher after alcohol withdrawal. The energy and macronutrient intakes did not significantly change during hospitalization. It is concluded that the modifications of HDL-cholesterol, HDL3-cholesterol, HDL2-cholesterol Apo A-I and Apo B values were induced by alcohol withdrawal in this population of chronic french alcoholics.

Adult↗

Triacylglycerol structure of human colostrum and mature milk.

Because triacylglycerol (TAG) structure influences the metabolic fate of its component fatty acids, we have examined human colostrum and mature milk TAG with particular attention to the location of the very long chain polyunsaturated fatty acid on the glycerol backbone. The analysis was based on the formation of various diacylglycerol species from human milk TAG upon chemical (Grignard degradation) or enzymatic degradation. The structure of the TAG was subsequently deduced from data obtained by gas chromatographic analysis of the fatty acid methyl esters in the diacylglycerol subfractions. The highly specific TAG structure observed was identical in mature milk and colostrum. The three major fatty acids (oleic, palmitic and linoleic acids) each showed a specific preference for a particular position within milk TAG: oleic acid for the sn-1 position, palmitic acid for the sn-2 position and linoleic acid for the sn-3 position. Linoleic and alpha-linolenic acids exhibited the same pattern of distribution and they were both found primarily in the sn-3 (50%) and sn-1 (30%) positions. Their longer chain analogs, arachidonic and docosahexaenoic acids, were located in the sn-2 and sn-3 positions. These results show that polyunsaturated fatty acids are distributed within the TAG molecule of human milk in a highly specific fashion, and that in the first month of lactation the maturation of the mammary gland does not affect the milk TAG structure.

Colostrum↗

Dependence of human milk essential fatty acids on adipose stores during lactation.

The relationships between essential fatty acid (EFA) composition of colostrum, mature milk, and white adipose tissue (WAT) were examined on days 5 and 30 postpartum in 24 healthy French mothers. Fatty acid composition was assessed by capillary gas chromatography. In WAT, the proportion of individual polyunsaturated fatty acids (PUFAs) did not change during lactation and was greater (18:2n-6) or lower (18:3n-3, long-chain PUFAs) than values found in colostrum or mature milk (P < 0.04). The 18:2n-6 content and the ratio of 18:3n-3 to 18:2n-6 correlated between WAT and colostrum (r = 0.52 and r = 0.57, respectively) or mature milk (r = 0.64 and r = 0.65, respectively). These relationships agree with an expected qualitative effect of WAT fatty acid composition on interindividual variability of milk parent EFA content. The decrease in the long-chain PUFA content observed from colostrum to mature milk and the concomitant occurrence of a precursor-product relationship between the linoleate and its long-chain PUFA are consistent with the mobilization of a preformed long-chain PUFA pool during early lactation.

Adipose Tissue↗

Fatty-acid composition of breast and iliac adipose tissue in breast-cancer patients.

In order to determine to what extent the fatty-acid composition of breast adipose tissue is representative of the body-fat composition in breast carcinoma, we compared the fatty-acid composition of breast adipose tissue to that of iliac fat in breast-cancer patients. Triglycerides from the 2 sites were purified by thin-layer chromatography and fatty-acid composition was determined by capillary gas chromatography. Compared with iliac fat, mammary fat was higher in saturated (33.2 +/- 3.9 vs. 24.4 +/- 1.6%; p = 0.0001) and lower in mono-unsaturated (48.0 +/- 2.2 vs. 54.8 +/- 2.7%; p = 0.0001) and poly-unsaturated fatty acids (16.6 +/- 3.7 vs. 18.0 +/- 3.1%; p = 0.0001). A positive correlation was found between the 2 sites for linoleate (r = 0.95; p = 0.0003), alpha-linolenate (r = 0.83; p = 0.01), palmitate (r = 0.78; p = 0.02) and palmitoleate (r = 0.76; p = 0.02). No relationship was observed for stearic and oleic acids. We conclude that breast and iliac fat differ with regard to fatty-acid composition. The interpretation of fatty-acid composition of the body stores in breast-cancer patients, as an indicator of long-term intake of dietary fat, should take into account the sampling site of stored lipids.

Adipose Tissue↗

Prognostic significance of tumor phosphatidylcholine stearic acid level in breast carcinoma.

The involvement of lipid enzymes in the action of oncogenes at the cell membrane level has suggested that membrane lipids could play a role in modulating the growth of tumors. We previously found that breast cancer patients with a low level of polyunsaturated fatty acids in their primary tumor's phosphatidylethanolamine had a high risk of early occurrence of visceral metastasis. In the present study, we prospectively examined whether fatty acid composition of tumor membrane phosphatidylcholine had a prognostic significance in a series of 63 patients with a localized presentation of breast cancer. Membrane phospholipids were extracted from the carcinoma tissue obtained at the time of surgery, phosphatidylcholine was purified, and its fatty acids were analyzed by capillary gas chromatography. During the follow-up period, 20 patients developed metastasis. In these patients, the proportion of stearic acid containing phosphatidylcholine was significantly lower than it was in the tumors of the 43 patients who remained metastasis-free. Multivariate analysis according to Cox showed that low stearic acid level in tumor phosphatidylcholine and high mitotic index were independently predictive of subsequent metastasis. The predictive value of stearic acid level on metastasis risk was higher in node-positive patients than in node-negative patients, allowing individualization of a subgroup of low stearic acid level, node-positive patients with very poor prognosis. We concluded that stearic acid level in tumor membrane phosphatidylcholine is an independent intra-tumor marker of breast cancer prognosis. This finding is new evidence that tumor's structural lipids are linked to the growth of breast cancer.

Adult↗

Age-related insulin resistance: a review.

Impaired glucose tolerance occurs with age. This impairment is multifactorial including a decrease in insulin-mediated glucose uptake by peripheral tissues and a delay in insulin-induced suppression of hepatic glucose output. A post-binding defect in insulin action such as a reduced capacity to transcribe more glucose transporter mRNA and/or a reduced translocation of preformed glucose transporters to plasma membrane is incriminated. However, insulin resistance with age is not a constant finding and other mechanism(s) has (have) to be involved in old individuals with impaired glucose tolerance and normal tissue insulin sensitivity.

Aging↗

Lactose and cataract in humans: a review.

In this review, the relationship between lactose and human cataract is examined from the presently available biochemical, metabolic, and epidemiological data. The exceptional cases of homozygous enzyme deficiency being excluded, fragmentary data give reason to believe that a risk of cataract secondary to lactose and galactose ingestion is present in certain subpopulations. In these population groups, the size of which is unknown, the lens could be exposed to intermittent episodes of hypergalactosemia due to the presence of a partial enzyme deficiency in the galactose metabolic pathway, and/or the persistence of a high adult jejunal lactase activity, and/or to a large and repeated consumption of either whole lactose or easily absorbed lactose (hydrolyzed forms and nonpasteurized yogurt).

Animals↗

Essential fatty acid composition of human colostrum triglycerides: its relationship with adipose tissue composition.

The relationships between essential fatty acid (EFA) composition of colostrum and white adipose tissue (WAT) were examined on day 5 after delivery in 69 healthy women. Fatty acid composition was assessed by capillary gas chromatography, and 33 fatty acids were detected in colostrum and in WAT. Total polyunsaturated fatty acid (PUFA) content was similar in colostrum and in WAT (15.7 +/- 3.1% and 16.1 +/- 3.8%, respectively), but long-chain PUFA content was higher in colostrum than in WAT (2.9 +/- 0.6% and 1 +/- 0.2%, respectively; P less than 0.001). The concentrations of linoleic acid were significantly correlated between colostrum and WAT (r = 0.77, P less than 0.0001). No correlation was found for alpha-linolenic acid. The relationships between long-chain PUFA composition of colostrum and WAT suggested that individual factors along with tissue specificity of the mammary gland are involved in either the capacity of desaturating and chain-elongating pathways and/or incorporation of long-chain PUFAs into colostrum.

Adipose Tissue↗

Plasma amino acid kinetics during acute states of glucagon deficiency and excess in healthy adults.

The effects of glucagon deficiency and excess on plasma leucine, lysine, and alanine were examined in six healthy young adult men, with primed continuous infusions of L-[1-13C]- or L-[5,5,5-2H3]leucine, L-[alpha-15N]-lysine, and L-[3-13C]alanine for 150 min before and during 210 min of either a glucagon-deficient euglycemic state (experiment 1), a basal glucagon state (experiment 2), or a glucagon-excess state (experiment 3). Steady-state plasma hormone levels were achieved by infusion of somatostatin (250 micrograms/h) and insulin (0.07 mU.kg-1.min-1), without (experiment 1) or with an infusion of glucagon at 0.7 ng.kg-1.min-1 (experiment 2) or 2.5 ng.kg-1.min-1 (experiment 3). Plasma branched-chain amino acid (AA) concentrations did not change with altered glucagon status, whereas significant differences were observed for plasma lysine, alanine, glycine, serine, threonine, proline, tyrosine, citrulline, and ornithine levels (0.05 greater than P greater than 0.001). Plasma leucine, lysine, and alanine fluxes and the rate of de novo alanine synthesis showed no significant changes with either glucagon deficiency or excess. These findings lead to the conclusion that glucagon-induced alterations in plasma AA profiles are not due to changes in the rate of appearance of AA from peripheral tissues but rather a consequence of changes in the fate of AA within the splanchnic region.

Adult↗

Metabolic effects of acarbose in young healthy men.

To explore the long-term metabolic effects of acarbose in man, 6 healthy men (25 +/- 2 years; BMI: 21.6 +/- 2.7) were fed a controlled diet in a metabolic ward for 7 consecutive weeks. After an initial 3-week period to ensure a metabolic steady-state, they received 300 mg/d of acarbose (100 mg before each meal) for the remaining 4 weeks. Stool and urine collections were made over 7 d on weeks 3 and 7. Faecal excretion of water, nitrogen, carbohydrate, fat, zinc, magnesium, copper, chromium, iron, calcium and phosphorus and urinary excretion of nitrogen, urea and calcium were measured. In addition, fasting and postprandial blood glucose and insulin levels, as well as fasting triglycerides, total cholesterol, apolipoproteins (Apo) A-I, A-II, and B, zinc and copper, vitamins A, B1, B2, B6, C, and E concentrations were measured before and at the end of the acarbose period. Weight, food consumption, and water balance were not modified by acarbose. Faecal nitrogen excretion increased significantly but the nitrogen balance remained positive. Faecal excretion of carbohydrate, fat, iron and chromium were significantly increased by acarbose. Apos A-I and A-II decreased significantly. Plasma levels of vitamin B6 increased and vitamin A concentrations decreased with acarbose. This study provides new insights into the metabolic effects of acarbose with respect to nitrogen, mineral and vitamin metabolism.

Acarbose↗