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L Casteilla

Publications and source records attributed to L Casteilla.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fast decline of hematopoiesis and uncoupling protein 2 content in human liver after birth: location of the protein in Kupffer cells.

Hepatic hematopoiesis is prominent during fetal life and ceases around birth. In rodent liver, the decline of the hepatic hematopoiesis starts abruptly at birth being accompanied by a decrease of mitochondrial uncoupling protein 2 (UCP2) expression in monocytes/macrophages, whereas hepatocytes may express UCP2 only under pathologic situations. The goals of this study were to characterize hepatic hematopoiesis in humans around birth, and to identify cells expressing UCP2. Hematopoiesis was evaluated histologically in the liver of 22 newborns (mostly very premature neonates), who died between 45 min and 140 d after birth, and one fetus. UCP2 expression was characterized by Northern blots, immunoblotting, immunohistochemistry, and by in situ hybridization. The number of hematopoietic cells started to decrease rapidly at birth, irrespectively of the gestational age (23-40 wk) of neonates. A similar decline was observed for UCP2 expression, which was relatively high in fetal liver. UCP2 was detected only in myeloid cells (mainly in Kupffer cells), but not in hepatocytes, although sepsis or other pathologies occurred in the critically ill newborns. Kupffer cells represent the major site of mitochondrial UCP2 expression in the human newborn. UCP2 may be essential for the differentiation and function of macrophages and serve as a marker for these cells in human liver during the perinatal period.

Down-Regulation↗
PubMed2000

The autonomic nervous system, adipose tissue plasticity, and energy balance.

In most mammals, two types of adipose tissue, white and brown, are present. Both are able to store energy in the form of triacylglycerols and to hydrolyze them into free fatty acids and glycerol. Whereas white adipose tissue can provide lipids as substrates for other tissues according to the needs of the organism, brown adipose tissue will use fatty acids for heat production. Over the long term, white fat mass reflects the net balance between energy expenditure and energy intake. Even though these two parameters are highly variable during the life of an individual, most adult subjects remain relatively constant in body weight throughout their lives. This observation suggests that appetite, energy expenditure, and basal metabolic rate are linked. An important characteristic of the adipose tissue is its enormous plasticity for volume and cell-number variations and an apparent change in phenotype between the brown and white adipose tissues. The present review focuses on the cellular mechanisms participating in the plasticity of adipose tissues and their regulation by the autonomic nervous system. There is compelling evidence with regard to the importance of the nervous system in the regulation of adipose tissue mass, either brown or white, by acting on the metabolic pathways and on the plasticity (proliferation, differentiation, transdifferentiation, apoptosis) of these tissues. A better comprehension of the different mechanisms involved in the feedback loop linking the brain and these two types of adipose tissue will lead to a better understanding of the pathophysiology of various disorders including obesity, cachexia, anorexia, and type II diabetes mellitus.

Adipocytes↗
PubMed2000

High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects.

OBJECTIVE AND DESIGN: As well as its involvement in control of adipose mass and body energy balance, several reports suggest a link between leptin and hemopoiesis. To test its putative role in human hemopoiesis, we developed a homologous system, ie recombinant human leptin treatment of purified CD34+ progenitors from adult human bone marrow. RESULTS: Leptin (50-100 ng/ml) significantly stimulated the appearance of granulocyte-macrophage colonies in the presence or absence of erythropoietin. The concentration of leptin required for this effect was rather high but within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocytosis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; (ii) leptin and leukocyte count were correlated only in obese subjects. Paracrine effects of locally released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochemistry revealing the close association of CD34+ cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these cells. CONCLUSION: These results indicate that leptin acts on human multilineage CD34+ cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progenitors.

Adult↗
PubMed2000

Regulation by cytokines of leptin expression in human bone marrow adipocytes.

Leptin is a hormone secreted by adipocytes. Besides controlling appetite and body weight, it has been suggested that leptin plays a role in inflammation and hemopoiesis. In this study we demonstrate that the pro-inflammatory/hemopoietic cytokines, IL-1beta, IL-6, TNF-alpha, and interferon-gamma, significantly inhibit gene expression and secretion of leptin by bone marrow adipocytes. These findings are in agreement with the data recently obtained from non-medullary adipose tissues. Within the bone marrow environment, leptin regulation by these pleiotropic cytokines could contribute to controlling the proliferation and differentiation of hemopoietic precursors as well as the maturation of stromal cells.

Adipocytes↗
PubMed2000

Correlation between pancreatic islet uncoupling protein-2 (UCP2) mRNA concentration and insulin status in rats.

Hypothesizing that UCP2 may influence insulin secretion by modifying the ATP/ADP ratio within pancreatic islets, we have investigated the expression of intraislet UCP2 gene in rats showing insulin oversecretion (non-diabetic Zucker fa/fa obese rats, glucose-infused Wistar rats) or insulin undersecretion (fasting and mildly diabetic rats). We found that in Zucker fa/fa obese rats, hyperinsulinemia (1222+/-98 pmol/l vs. 128+/-22 pmol/l in lean Zucker rats) was accompanied by a significant increase in UCP2 mRNA levels. In rat submitted to a 5 day infusion with glucose, hyperinsulinemia (1126+/-101 pmol/l vs. 215+/-25 pmol/l in Wistar control rats), coincided with an enhanced intraislet UCP2 gene expression, whereas a 8h or a 2 day-infusion did not induce significant changes in UCP2 mRNA expression. In rats made hypoinsulinemic and mildly diabetic by the injection of a low dose of streptozotocin, and in 4-day-fasting rats (plasma insulin 28+/-5 pmol/l) UCP2 gene expression was sharply decreased. A 3-day-fast was ineffective. The data show the existence of a time-dependent correlation between islet mRNA UCP2 and insulin that may be interpreted as an adaptative response to prolonged insulin excess.

Analysis of Variance↗
PubMed2000

Inflammatory/haematopoietic cytokine production by human bone marrow adipocytes.

Adipocytes are now considered as secretory and endocrine cells. White and brown adipocytes synthesize and secrete a variety of cytokines, among a number of peptide and non-peptide products. Some of these cytokines, particularly IL-6 and TNF-alpha, appear multifunctional since they may be involved in the control of adipose mass, inflammatory response and haematopoiesis. Bone marrow adipocytes are another abundant type of adipocytes, but their precise role in humans is poorly understood. In the present study, we demonstrate that, in contrast to non-medullary adipocytes, human bone marrow adipocytes in primary culture secrete only trace amounts of IL-1 beta and TNF-alpha, but, they secrete significant and regulated levels of IL-6. These results reinforce the concept of functional heterogeneity of adipose tissues according to their anatomical localization, and indicate that bone marrow adipocytes may contribute to the complex network of cytokines involved in the control of haematopoiesis.

Adipocytes↗
PubMed1999

Inverse distribution of uncoupling proteins expression and oxidative capacity in mature adipocytes and stromal-vascular fractions of rat white and brown adipose tissues.

To investigate relationships between the uncoupling protein (UCP) family and oxidative metabolism in fat pads, we measured the cytochrome oxidase activity, used as an index of oxidative capacity, and the mRNA content encoding UCP1, UCP2 and UCP3. Most oxidative potential was found in the stromal-vascular fraction (SVF) of brown fat and in mature adipocytes of white fat (inguinal and periovarian). Considering the whole fat pads, the oxidative potential observed in mature white adipocytes fraction was not negligible compared with that of brown adipocytes fraction. UCP1 and UCP3 were expressed exclusively in mature brown adipocytes. Whatever the deposit, UCP2 mRNA was mainly localized in the SVF. These results indicate that, in fat, high oxidative potential is not necessarily linked to high UCPs transcripts content and point out the oxidative capacity of SVF from brown fat.

Adipocytes↗
PubMed1999

A role for preadipocytes as macrophage-like cells.

Several lines of evidence have supported a link betweeen adipose tissue and immunocompetent cells. This link is illustrated in obesity, where excess adiposity and impaired immune function have been described in both humans and genetically obese rodents. In addition, numerous factors involved in inflammatory response are secreted by both preadipocytes and macrophages. Here we show that proliferating preadipocytes in cell lines and primary cultures, develop phagocytic activity toward microorganisms. This is demonstrated by phagocytosis assays and confocal microscopy. This function disappears when preadipocytes stop proliferating and differentiate into adipocytes. After phagocytosis, preadipocytes show microbicide activity via an oxygen-dependent mechanism. In addition, preadipocytes as well as adipocytes are stained with MOMA-2, a marker of monocyte-macrophage lineage, but are negative for specific mature macrophage markers (F4/80 and Mac-1). These results suggest that preadipocytes could function as macrophage-like cells and raise the possibility of a potential direct involvement of adipose tissue in inflammatory processes.

Adipocytes↗
PubMed1998

Expression of specific white adipose tissue genes in denervation-induced skeletal muscle fatty degeneration.

Denervation of skeletal muscle results in rapid atrophy with loss of contractile mass and/or progressive degeneration of muscle fibers which are replaced to a greater or lesser degree by connective and fatty tissues. In this study, we show that denervated rabbit muscles are transformed into a white adipose tissue, depending on their fiber types. This tissue does express LPL, G3PDH and particularly the ob gene, a white adipose tissue-specific marker, and does not express the brown adipose tissue molecular marker UCP1 mRNA.

Adipose Tissue↗
PubMed1998

High expression of uncoupling protein 2 in foetal liver.

To assess the putative role of mitochondrial uncoupling protein 2 (UCP2) during perinatal development, its expression was analysed in mice and rats. Expression was detected in a large range of foetal tissues. A unique developmental pattern of UCP2 expression was found in liver, where the level of UCP2 mRNA was about 30-fold higher in foetuses than in adults (mice data), and started to decline immediately after birth. Neither UCP1 nor UCP3 mRNA was expressed in foetal liver. As in adult liver, immunohistochemical analysis suggested exclusive localisation of UCP2 in the monocyte/macrophage cells. Our results indicate a role of UCP2 in haematopoietic system development.

Animals↗
PubMed1998

Lipolytic and antilipolytic responses of the Siberian hamster (Phodopus sungorus sungorus) white adipocytes after weight loss induced by short photoperiod exposure.

Short day photoperiod promotes thermogenesis and extensive weight loss in Siberian hamsters (Phodopus sungorus sungorus). To determine whether a change in hormone-sensitive lipolysis occurs after short-photoperiod exposure, some lipolytic responses were measured on white adipocytes isolated from animals exposed in warm conditions to short or Long daylight photoperiod. The body mass of male Siberian hamsters exposed during 11 weeks to short days (SD; light: dark, 6:18 hr) reached only 50% of those kept in long days (LD; 16: 8 hr). In SD-hamsters, adipose depot mass also represented approximately 50% of the LD group. A lower DNA content was observed in intra-abdominal fat pads of SD-hamsters. Lipolytic responses to noradrenaline, adrenaline, isoproterenol and ACTH were unchanged. However, sensitivity to the beta-3 adrenergic agonist, BRL 37344, was moderately increased. The major component of the adrenergic control of lipolysis was mediated by beta-3 adrenoceptors in both LD- and SD-Siberian hamsters. The limited antilipolytic effect of alpha-2 adrenergic agonists, PYY or insulin was rather surprising in Siberian hamsters since these inhibitory systems are efficient in hibernants and other photoperiod-sensitive rodents. Our results show that, after short photoperiod exposure, white adipose tissue mass and DNA content are reduced, especially in the epididymal fat pad, with only minor changes in the adipocyte sensitivity to lipolytic hormones.

Adipocytes↗
PubMed1998

High expression of leptin by human bone marrow adipocytes in primary culture.

Adipocytes participate in the microenvironment of the bone marrow (BM), but their exact role remains to be determined. It has recently been shown that leptin, a hormone secreted from extramedullary adipocytes, could be involved in hematopoiesis. Therefore we have developed a primary culture system of human BM adipocytes to characterize their differentiation and determine whether leptin is also secreted from these adipocytes. BM cells were cultured with fetal calf and horse sera. In the presence of dexamethasone, cells with vesicles containing lipids appeared within 15 days. They expressed glycerol phosphate dehydrogenase activity and a lipolytic activity in response to isoproterenol, but expressed neither the adrenergic beta3 receptor nor the mitochondrial uncoupling protein UCP1. The addition of insulin alone to the culture media did not promote adipocyte differentiation. Leptin was expressed and secreted at high levels during adipocyte differentiation. Acute exposure of differentiated adipocytes to insulin had little effect on leptin expression whereas forskolin strongly inhibited it. These results show that although human BM adipocytes differ from extramedullary adipose tissues in their sensitivity to different effectors, they are a secondary source of leptin production. They suggest that BM adipocytes could contribute to hematopoiesis via the secretion of leptin in the vicinity of hematopoietic stem cells.

Adipocytes↗
PubMed1997

Characterization of a melatonin binding site in Siberian hamster brown adipose tissue.

Melatonin has been shown, in various rodent species, to mediate photoperiodic effects on body weight and, consequently, fat mass. Pharmacological investigations indicated that the brown adipose tissue of Siberian hamsters possesses a melatonin binding site with a dissociation constant of 570+/-300 pM and a density of 3.2+/-1.8 fmol/mg protein. This binding site can also be detected on mature brown adipocyte membranes. The rank order of potency of a variety of drugs to displace 2-[125I]iodomelatonin from binding sites on Siberian hamster brown adipose tissue was as follows: 2-iodomelatonin > melatonin = prazosin > GR135531 (5-methoxycarbonylamino-N-acetyltryptamine) > N-acetylserotonin > 6-chloromelatonin > S20304 (N-(2-(1-naphthyl)ethyl)cyclobutanecarboxamide) >> methoxamine, phenylephrine, serotonin. Mel(1a) mRNA was not detected by RT-PCR (reverse transcription-polymerase chain reaction) in brown adipose tissue. Melatonin had no effect on either basal or stimulated lipolysis. Moreover, melatonin did not modify intracellular cAMP accumulation or inositol phosphate content. Together, these results suggest that the melatonin binding site characterized in brown adipose tissue is clearly different from the Mel(1) cloned subtype and has some features different from those of the Mel2 subtype.

Adipose Tissue, Brown↗
PubMed1997

Kupffer cells are a dominant site of uncoupling protein 2 expression in rat liver.

The mechanisms underlying thermogenesis in liver are not well understood. They may involve proteins related to the mitochondrial uncoupling protein (UCP1) of brown adipocytes. In this paper, it is demonstrated that UCP1 is not expressed in any liver cell type of rat while UCP2, a recently cloned homologue of UCP1, is expressed at a very high level in Kupffer cells but not in hepatocytes. This high level of expression of UCP2 in Kupffer cells allowed cross immunoreactivity with antibodies directed against UCP1. This cross reactivity was confirmed by the detection of UCP2 with anti-UCP1 antibody, in western blotting analysis of transfected yeasts expressing rat UCP2. The high level expression of UCP2 in Kupffer cells suggests a particular function of UCP2 in macrophages.

Animals↗
PubMed1997

A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation.

According to the state of mitochondrial respiration, the respiratory chain generates superoxide anions converted into hydrogen peroxide. Two uncoupling proteins (UCP) able to modulate the coupling between the respiratory chain and ATP synthesis are now identified and could be involved in mitochondrial H2O2 generation. UCP1 is specific to brown adipose tissue (BAT) whereas UCP2 is expressed in numerous tissues, particularly in monocytes/macrophages. Preincubation of BAT mitochondrial fractions with GDP, an inhibitor of UCP1, induced a rise in mitochondrial membrane potential (assessed by rhodamine 123 uptake) and H2O2 production. An uncoupling agent reversed this effect. Liver mitochondria exhibited a similar phenotype. GDP was also able to raise membrane potential and H2O2 production of the mitochondria from nonparenchymal cells expressing UCP2, but was completely ineffective on mitochondria from hepatocytes deprived of UCP2. The GDP effect was also observed with mitochondrial fractions of the spleen or thymus, which highly expressed UCP2. Altogether, these results strongly suggest that UCP2 is sensitive to GDP and that the UCPs, particularly UCP2, are able to modulate H2O2 mitochondrial generation. This supports a role for UCP2 in cellular (patho-) physiological processes involving free radicals generated by mitochondria, such as oxidative damage, inflammation, or apoptosis.

Adipose Tissue, Brown↗
PubMed1996

Expression of c-erbA alpha, c-erbA beta and Rev-erbA alpha mRNA during the conversion of brown adipose tissue into white adipose tissue.

The levels of mRNA encoding uncoupling protein (UCP), thyroid hormone receptors (c-erbA alpha, c-erbA beta) and a related protein Rev-erbA alpha have been studied in brown (pericervical) and white (perirenal) rabbit adipose tissues from birth to 180 days. The c-erbA alpha and c-erbA beta genes are expressed at similar levels in the two tissues. The alpha 1, alpha 2 and beta 1 transcripts do not change notably during development or during the conversion from brown to white phenotype which occurs in pericervical during postnatal life. Rev-erbA alpha mRNA is barely detectable at birth and dramatically increases between 7 and 30 days. However, this increase is not tissue-specific and is also observed in liver and heart. In conclusion, our results show that the decline in UCP expression during the transition from brown to white phenotype cannot be related to changes in the profiles of thyroid hormone receptors or Rev-erbA alpha mRNA expression. These profiles are not different between adipose tissue sites which are brown or white at birth.

Adipose Tissue↗