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D Gripois

Publications and source records attributed to D Gripois.

At least 19 recordsLinked to original sources

Fat-depleted CLA-treated mice enter torpor after a short period of fasting.

Resting energy expenditure (Resting-EE), EE with treadmill exercise, and post-prandial thermogenesis were continuously monitored by indirect calorimetry during a 24 h recording session in control (CT) and CLA-treated (CLA) (1% CLA in the food, by weight) C57Bl/6 male mice. After 15 days of CLA treatment, the fat content of CLA mice had fallen to 20% of that in CT mice. CLA mice were able to face the energy challenge of exercise but used less lipid than CT mice. Resting-EE values fell during the post-exercise period. The thermogenic response to a calibrated test meal given 5 h after the run abolished the differences in EE and substrate oxidation between CT and CLA mice. However, 2.5 h after ingestion of the test meal onward, CT mice gradually increased their lipid oxidation to sustain resting-EE levels. In contrast, CLA mice did not increase their lipid oxidation and their resting-EE levels fell significantly until they entered into torpor. Blood leptin was low but similar in CT and CLA-treated mice suggesting that leptin is not critical to induce torpor. We suggest that the durable inhibition of lipid oxidation in fasting CLA mice was an adaptive behaviour devoted at sparing the residual adipose deposits.

Animals↗

Postprandial variations in the cholesteryl ester transfer protein activity, phospholipid transfer protein activity and plasma cholesterol efflux capacity in normolipidemic men.

BACKGROUND AND AIM: Plasma cholesterol efflux capacity is stimulated during postprandial (PP) hypertriglycerdemia. Plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are the key proteins in lipoprotein metabolism and remodelling, but their role during the PP cholesterol efflux process remains indeterminate. The aim of this study was to determine the effect of a fatty meal intake on plasma CETP and PLTP activities, and the capacity of plasma to promote cholesterol efflux, as well as to evaluate the relationship between these three key mechanisms of the reverse cholesterol transport process. METHODS AND RESULTS: CETP and PLTP activities and the cholesterol efflux capacity of plasma were measured over eight hours following a fatty meal (1000 kcal, 62% fat) in 13 normolipidemic men. CETP activity and the cholesterol efflux capacity of plasma from Fu5AH cells increased after the meal, reaching a maximum after eight hours (respectively 32%, p = 0.06, and 6.5%, p = 0.045), whereas PLTP activity remained unchanged. CETP and PLTP activities did not correlate with plasma cholesterol efflux capacity in the fasting or PP state. Plasma CETP activity in the fasting state positively correlated with the plasma non-esterified fatty acid (NEFA) levels, but no correlation was found with any lipid or apolipoprotein postprandially. The cholesterol efflux capacity of plasma correlated positively with high-density lipoprotein (HDL) components, the best correlation being with the HDL phospholipid fraction in both the fasting and PP states. CONCLUSIONS: These findings suggest that plasma CETP and PLTP activities in healthy normolipidemic subjects are differently regulated in the PP state, and are not correlated with the increased cholesterol efflux capacity of PP plasma. HDL-phospholipid remains the key factor in the regulation of the capacity of plasma to promote Fu5AH cell cholesterol efflux.

Adult↗

Diet-dependent effects of insulin infusion on the hepatic lipoprotein receptors and the key enzymes of bile acid synthesis in the hamster.

The effects of an induced hyperinsulinemia on both the cholesterol and bile acid metabolisms were analyzed in the hamster. The role of dietary sucrose as modulator of these effects was evaluated by feeding the animals with two semi-synthetic diets containing a low (SD, 20%) and a high (LD, 62.5%) sucrose proportion. Hamsters fed under basal nutritional conditions (chow diet, CD) were also used. LD enabled the consequences of an insulin infusion on cholesterol gallstone formation to be evaluated. Subcutaneous osmotic pumps were implanted in all the animals and delivered either 3 IU/day of insulin (insulin groups: CDI, SDI, LDI) or saline (control groups: CDC, SDC, LDC). Several parameters bound to lipid metabolism were measured. The plasma cholesterol concentration remained constant in all the insulin treated groups compared to the controls. Phospholipid and triglyceride concentrations decreased in both the plasma and liver in the CDI and SDI groups. A lower SR-BI mass (around 50%) was found in the liver of CDI and SDI hamsters with concomitant higher hydroxy-methyl-glutaryl coenzyme A reductase activity. The LDL-receptor mass and cholesterol 7alpha-hydroxylase activity in the LDI group were both decreased (-47%, -71% respectively). No variations in the cholesterol gallstone incidence were observed. In conclusion, chronic insulin infusion in growing hamsters induced similar effects on cholesterol metabolism in the CD and SD groups but different ones, between diets containing a low (SD) and a high (LD) sucrose proportion. The distribution of triglycerides and phospholipids in the plasma, liver and bile was also affected by the insulin infusion.

Animals↗

Insulin injections enhance cholesterol gallstone incidence by changing the biliary cholesterol saturation index and apo A-I concentration in hamsters fed a lithogenic diet.

BACKGROUND/AIMS: A link between insulin and cholesterol gallstone disease has often been suspected but never demonstrated. The aim was to evaluate the direct implication of insulin in the gallbladder cholesterol gallstone formation process. METHODS: Hamsters fed with a soft-inducing lithogenic diet, enriched with sucrose, were injected daily, for 1 week, either with long-acting insulin or saline (controls). RESULTS: Insulin injections doubled the cholesterol gallstone incidence. The cholesterol saturation index (CSI) of bile significantly increased (+19%) and biliary apolipoprotein A-I (apo A-I) decreased, both in concentration (-71%) and the proportion relative to the total biliary proteins (-25%). No modifications in the biliary bile acid composition were noticed. Hepatic HMGCoA reductase activity was higher (+341%), CYP7A1 activity was lower (-52%), whereas CYP27A1 and CYP7B1 were not affected. The hepatic low-density liprotein (LDL)-receptor and SR-BI masses did not vary. The hepatic total cholesterol content increased (+42%). Fasting plasma phospholipid and triglyceride concentrations significantly decreased (-15 and -60%, respectively), but the cholesterol concentration remained constant. CONCLUSIONS: These results suggest that insulin injections enhance cholesterol gallstone incidence by increasing the CSI of bile and decreasing the concentration and proportion of a biliary anti-nucleating protein, apo A-I. Insulin modulates the major enzymes of cholesterol and bile acid metabolisms in vivo.

Animals↗

Short and long-term effects of streptozotocin on dietary cholesterol absorption, plasma lipoproteins and liver lipoprotein receptors in RICO rats.

Adult male genetically hypercholesterolemic RICO rats were studied 6 and 28 days after streptozotocin (STZ) administration together with untreated RICO controls. The absorption coefficient of dietary cholesterol was determined using dual-isotope blood ratio method. Plasma lipoproteins as well as fecal neutral sterols and bile acids were analysed at both experimental times. Liver lipid parameters were measured and lipoprotein receptors (LDLr, SR-BI and HB2) were assayed by immunodetection. Six days after STZ administration, dietary cholesterol absorption was more efficient (+49%) in treated rats than in controls, and stayed higher (+68%) in the diabetic rats sacrificed at day 28. Fecal neutral sterol elimination decreased soon after STZ administration (by 35% at day 6), due to a higher cholesterol absorption coefficient, then increased to control level at day 28, due to installed diabetes-induced hyperphagia. Comparison of the lipoprotein profiles indicated that the concentration of HDL1. which is typically high in control Rico rats, fell significantly in diabetic rats at both experimental times, whereas that of HDL2 increased only at day 28. In diabetic rats, an early and strong enhancement of the hepatic expression of SR-BI appeared at day 6 (+415%) and persisted at day 28, but at a lesser extent (+85%). The expression of LDLr and HB2 was unchanged at day 6, but was significantly modified at day 28 (+140% for LDLr and -50% for HB2). These data show that streptozotocin-induced diabetes in Rico rats results in modifications of the expression of liver lipoprotein receptors which can contribute to alterations of the lipoprotein profile.

Animals↗

Effects of insulin deficiency on lipoproteins and their hepatic receptors in Rico rats.

The present study was designed to examine the effect of streptozotocin (STZ)-induced diabetes on the plasma lipoprotein profile and hepatic expression of the LDL receptor and HDL binding protein (HB2) in hypercholesterolemic Rico rats. The plasma level of HDL1 (density range 1.040-1.063), which is particularly high in this rat strain, decreased (-25%) 28 d after STZ administration (50 mg/kg). In contrast, the treatment increased (+54%) the plasma concentration of HDL2 (density range 1.063-1.210). These variations in the lipoprotein concentrations were associated with inverse changes in the hepatic protein levels of the LDL receptor (+118%) and HB2 (-46%). These results suggest that the hepatic expression of HB2, a putative HDL receptor, can influence the plasma level of apo Al-rich HDL as has already been shown for the LDL receptor for apo B/E containing lipoproteins.

Animals↗

Influence of cold exposure on dopamine content in rat brown adipose tissue.

Cold exposure produces a large increase in rat brown adipose tissue (BAT) dopamine (DA) content. This increase is rapid (30 min of cold are sufficient to produce a maximal effect), and can be detected at different ages (from birth to adulthood). Cold also greatly increases DA turnover rate in BAT. In the same experimental conditions tyrosine hydroxylase is activated, while the activity of dopamine-beta-hydroxylase is not modified. The possibility that DA can regulate BAT functioning is discussed.

Adipose Tissue, Brown↗

Decreased norepinephrine turnover rate in the brown adipose tissue of pre-obese fa/fa Zucker rats.

Norepinephrine (NE) content and turnover rate, and the activity of dopamine-beta-hydroxylase (DBH) were measured in the brown adipose tissue (BAT) of developing Zucker rats of the three genotypes: Fa/Fa and Fa/fa (with a lean phenotype) and fa/fa (phenotypically obese). As early as 15 days of age, namely at a pre-obese stage, BAT NE content and turnover rate are already reduced in fa/fa rats, just like they are at 50 days. The development of DBH activity is completely impaired in fa/fa rats. These results demonstrate that the reduction in sympathetic tone in BAT of fa/fa rats is already present before the onset of phenotypic obesity.

Adipose Tissue, Brown↗

Striatal dopamine metabolism is differentially affected by insulin according to the genotype in Zucker rats: a microdialysis study.

The genetically obese Zucker rat presents several abnormalities related to insulin and brain monoamines, which may play a role in its impaired regulation of food intake and body weight. In a previous study, the possible insulin-monoamine interplay was investigated by measuring brain monoamine and metabolite levels in the three genotypes of the Zucker strain. In addition to the expected results, insulin had a particular effect on striatal dopamine (DA) release, regardless of ponderal status and genotype. We further investigated this point in the present study, using the brain microdialysis technique in the striatum. Lean homozygous Fa-Fa rats responded as expected to insulin with regard to striatal DA release, with increases in DA and 3-methoxy-tyramine levels and decreases in dihydroxyphenylacetic acid and homovanillic acid. Lean heterozygous Fa-fa rats showed a very specific response profile, with decreases in all dopaminergic parameters, suggestive of an effect on DA synthesis rather than DA release. This further emphasizes the marked differences between homozygous and heterozygous lean rats. The obese fa-fa rats clearly fell into two populations. The first showed a profile of response to insulin similar to that of the lean Fa-fa rats, in keeping with the disturbances related to the "fa" gene. The second showed an increase in all the dopaminergic parameters. This pattern of response was, however, different from that of the Fa-Fa rats. These opposing responses in the two obese populations did not reflect differences in the blood glucose response to insulin. One explanation is that 16 wk may be a critical transition period in the development of genetic obesity, with regard to brain monoamine disturbances and the response to insulin.

3,4-Dihydroxyphenylacetic Acid↗

Splicing of juvenile and adult tau mRNA variants is regulated by thyroid hormone.

The effect of thyroid hormone on the expression of tau transcripts was studied during postnatal brain development. The level of tau mRNA was only slightly changed postnatally in the cerebral hemispheres of hypothyroid rats, whereas the level of tau mRNA in the cerebellum was maintained at a higher level than in the euthyroid controls. As shown by in situ hybridization studies, such an alteration in tau mRNA expression can be ascribed to an effect of thyroid hormone on the rate of migration of the granule cells in the cerebellum; that tau mRNAs remain high in the cerebellum as long as the granule cells are migrating correlates with the observation that hypothyroidism slows the rate of migration of granule cells. RNase protection assays also showed that thyroid hormone deficiency delays the transition between the immature and mature tau transcripts in both brain regions. Thus, one of the effects of thyroid hormone is to regulate the splicing mechanism that allows replacement of the juvenile tau variants by the adult entities during neuronal differentiation.

Animals↗

Tyrosine hydroxylase and dopamine beta-hydroxylase inductions evoked by reserpine in the superior cervical ganglion of developing eu- and hypothyroid rats.

This study was designed to determine the effect of neonatally-produced hypothyroidism on reserpine-elicited tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (D beta H) induction in the superior cervical ganglion (SCG) in rats. Some rats were rendered hypothyroid from birth by daily treatment with propylthiouracil (PTU). Some hypothyroid rats received replacement therapy with triiodothyronine (T3). Some rats received PTU for 20 days, beginning at 90 days of age. Some rats were not treated and served as controls. TH and D beta H activities were assayed at 30, 50 and 110 days of age. Basal TH activity in the SCG for rats made hypothyroid as neonates was significantly lower than for controls at all ages tested; basal D beta H activity for these rats was lower than for controls at 30 and 50 days of age, but by 110 days was not different from that for controls. Basal TH activity for rats made hypothyroid as adults was intermediate between that for controls and rats made hypothyroid from infancy. Injecting control rats with reserpine produces a robust TH induction in the SCG at each age tested, and a strong D beta H induction at 50 and 110 days of age. Reserpine-evoked TH and D beta H inductions in rats made hypothyroid as adults were not different from those seen in controls. In contrast, rats made hypothyroid from infancy showed virtually no evidence of a reserpine-provoked TH or D beta H induction at any age tested. TH and D beta H inductions for hypothyroid rats given T3 replacement were completely normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effects of insulin on brain monoamine metabolism in the Zucker rat: influence of genotype and age.

Disturbances of insulin or brain monoamine metabolism may play a role in the impaired regulation of food intake and body weight in the obese Zucker rat. We investigated a possible insulin-monoamine interaction by measuring monoamine levels in the hypothalamus and striatum of obese (fa-fa) and lean (Fa-Fa and Fa-fa) Zucker rats after peripheral insulin administration. The classically reported effects of insulin, i.e., increases in tryptophan, 5-hydroxy-indolacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) levels, were observed in the hypothalamus of Fa-Fa and Fa-fa rats, but not in obese fa-fa rats. Given the mechanism of action of insulin, this lack of effect in the obese rats may be related to the peripheral insulin resistance they exhibit. Furthermore, given the role of these monoaminergic systems, this reduced effect may be related to the impaired regulation of food intake and body weight. At 8 wk of age, however, insulin restored the decreased basal 5-HIAA levels observed in the obese rats. Increase in 5-HIAA levels following insulin administration appeared in the striatum of Fa-Fa rats only, suggesting that, as for brain insulin content, other central insulin-related disturbances may be related to the presence of the "fa" gene. In addition, certain effects of insulin on striatal dopamine release were observed in only the Fa-Fa and fa-fa rats, suggesting a particular disturbance related to the heterozygous character. This latter point calls for further investigations on the central dopaminergic effects of insulin.

3,4-Dihydroxyphenylacetic Acid↗

Regulation of five tubulin isotypes by thyroid hormone during brain development.

Nucleic acid probes derived from the 3' noncoding region of five tubulin cDNAs were used to study the effects of thyroid hormone deficiency on the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2)- and three beta (beta 2, beta 4, and beta 5)-tubulin isotypes in the developing cerebral hemispheres and cerebellum. The content of alpha 1, which markedly declines during development in both brain regions, is maintained at high levels in the hypothyroid cerebellum, whereas it is decreased in the cerebral hemispheres. The alpha 2 level also declines during development and is decreased in both regions by thyroid hormone deficiency, but only during the two first postnatal weeks. Thyroid hormone deficiency slightly increases at all stages the beta 2 level in the cerebellum, whereas a decrease is observed at early stages in the cerebral hemispheres. The beta 5 level seems to be independent of thyroid hormone in the cerebral hemispheres, whereas it decreases at early stages in the hypothyroid cerebellum. Finally, the expression of the brain-specific beta 4 isotype is markedly depressed by thyroid hormone deficiency, particularly in the cerebellum. These data suggest that the genes encoding the tubulin isotypes are, directly or not, differently regulated by thyroid hormone during brain development. This might contribute to abnormal neurite outgrowth seen in the hypothyroid brain and therefore to impairment in brain functions produced by thyroid hormone deficiency.

Aging↗

Activity of enzymes involved in norepinephrine biosynthesis in the brown adipose tissue of the developing rat. Influence of hypothyroidism.

The activities of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) were measured in vitro in the brown adipose tissue (BAT) of control and hypothyroid developing rats. Neonatal hypothyroidism slows the development of TH activity, as manifest in lower BAT TH activity, relative to controls, up to 20 days. This effect is more pronounced when the onset of hypothyroidism is induced prenatally. No clear effect of hypothyroidism on DBH activity was evident.

Adipose Tissue, Brown↗