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Biomedical subjects

B Cousin

Publications and source records attributed to B Cousin.

17 recordsLinked to original sources
PubMed2001

Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity.

We recently demonstrated that preadipocytes exhibit functional features of macrophages, such as phagocytosis and anti-microbial activity, suggesting that preadipose cells could play a role in the inflammatory process or immune response. The aim of this study was to compare these functions of both macrophages and cells from stroma-vascular fraction (SVF) of the adipose tissue in two different situations, obesity and inflammation, characterized by alterations in immune responsiveness. We demonstrated that ob/ob mice exhibited strong decrease in antimicrobial activity of both macrophages and SVF. This defect is compensated in SVF, at least in part, by an enhancement of phagocytosis that does not seem to be due to an increased macrophage number. In vitro leptin treatment of SVF and macrophages from obese mice did not restore their immune defects. Thioglycollate treatment of lean and obese mice induced an inflammatory process that led to an increase in macrophage activity in both strains. This stimulation also observed in SVF from lean mice is not present in obese ones. This work demonstrated that SVF immune functions could be modified in different pathological situations such as inflammation and obesity and sustained the new physiological role of preadipocytes in these processes.

Adipocytes↗
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↗
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

Lack of melatonin effects on insulin action in normal rats.

Despite a large number of studies, the role of melatonin on glucose metabolism is still controversial. The aim of the present work was to further characterize the effect of melatonin on insulin action during: i) intravenous insulin tolerance test performed at different times of the day using melatonin, a melatonin agonist (S-20304), a melatonin antagonist (S-20928) or in pinealectomized rats. ii) euglycemic-hyperinsulinemic clamp performed in melatonin agonist-treated as well as in pinealectomized rats. The fall in glycemia after the insulin injection was not significantly affected by melatonin and melatonin agonist (S-20304) at ZT6, nor by the melatonin antagonist (S-20928) at ZT13 nor in pinealectomized animals at ZT6 in comparison to their respective control. Acute treatment with S-20304 or chronic suppression of melatonin by pinealectomy did not significantly alter basal plasma glucose and insulin levels or hepatic glucose production and whole body or individual tissue glucose utilization. These data do not give support to a crucial role of melatonin on insulin action in normal rats.

Animals↗
PubMed1997

Developmental changes in integrin beta-subunits in rat cerebral cortex.

The present study was carried out to characterize the developmental expression of beta 1-, beta 5- and beta 6-integrin subunits in rat cerebral cortex. Using reverse transcriptase-polymerase chain reaction, mRNA of the three beta-subunits were shown to be present at all developmental stages. Based on immunoblots, beta 1-subunit expression was decreased during cortical development from embryonic stages to adults. beta 6-subunit expression appeared only in adult cortex. beta 5-subunit expression did not change during development. These beta-subunits were expressed in cortical embryonic cells as revealed by immunological studies in vitro. beta 5 and beta 6 were also present in neuronal cells and in oligodendrocytes in adult cortex. Altogether, these results demonstrate that rat cerebral cortex expresses distinct integrin beta-subunits with different developmental profiles. This switch of beta-subunits may be an important mechanism for the regulation of cell behaviour during development.

Animals↗
PubMed1996

Cellular changes during cold acclimatation in adipose tissues.

Cold exposure is a well-known physiological stimulus that activates the sympathetic nervous system and induces brown adipose tissue (BAT) hyperplasia. The effects of cold exposure or cold acclimatation have been extensively studied in interscapular BAT (IBAT). However, it has been recently shown that studied adipocytes are present in adipose deposits considered as white fat such as periovarian (PO) fat pad. We have investigated the kinetic of brown precursor recruitment in adipose tissues using DNA measurement and specific marker expression. In IBAT, cold exposure induces proliferation of precursor cells and differentiation into preadipocytes characterized by the expression of A2COL6, a marker specific to early steps of the differentiation process. A chronic stimulation of the tissue is necessary to observe the full effect. In PO fat pad, no proliferation can be detected, whereas differentiation of brown preadipocytes and maybe phenotypic conversion of white adipocytes seems to be promoted. In conclusion, these data demonstrated that 1) the same stimulus (cold exposure) does not induce the same response in terms of preadipocyte proliferation and differentiation in periovarian and brown adipose tissues, although both contain brown adipocytes, and 2) preadipocyte recruitment in adipose tissues after cold exposure depends on the predominant type of fat cells.

Adaptation, Physiological↗
PubMed1996

Changes in autonomic nervous system activity and consecutive hyperinsulinaemia: respective roles in the development of obesity in rodents.

The autonomic nervous system plays a major role in metabolism regulation by modulating metabolic pathways directly or indirectly via control of hormone (particularly insulin) secretion in various organs and tissues. In addition, the system modulates the proliferation and differentiation of some cell types. This activity is directly controlled by certain brain areas, particularly those located in the hypothalamus. A feedback loop signals metabolic changes at the periphery to these brain areas. This review focuses on the role of the autonomic nervous system in the activity and plasticity of pancreas and adipose tissues under normal conditions or in obesity, with special attention to the importance of alterations in these functions.

Adipose Tissue↗
PubMed1993

Adipose tissues from various anatomical sites are characterized by different patterns of gene expression and regulation.

We have shown previously the presence of brown adipocytes among white fat pads, and proposed the existence of a spectrum of adipose depots according to the abundance of brown fat cells [Cousin, Cinti, Morroni, Raimbault, Ricquier, Pénicaud and Casteilla (1992) J. Cell Sci. 103, 931-942]. In this study, we tried to characterize this spectrum better. We determined in several adipose depots (i) the richness of pre-adipose cells, as assessed by A2COL6 mRNA levels; (ii) whether a fat pad was characterized by a pattern of mRNA expression; (iii) whether this pattern was close related to abundance of brown adipocytes, and (iv) whether the regulation of this pattern by catecholamines under cold exposure or beta-agonist treatment was similar in the different pads. This was achieved by studying proteins involved in glucose and lipid metabolism such as insulin-sensitive glucose transporter (GLUT4), fatty acid synthase, lipoprotein lipase and fatty acid binding protein aP2, as well as beta 3-adrenergic-receptor expression. Among white adipose depots, the periovarian fat pad was characterized by the highest content of pre-adipocytes and of brown adipocytes, and inguinal fat by the highest lipogenic activity potential. There was no close correlation between beta 3-adrenergic-receptor expression and brown adipocyte content in the tissues, as measured by the degree of uncoupling protein (UCP) gene expression. However, in pads expressing UCP mRNA, mRNA levels of beta 3-adrenergic receptor and other markers were increased in parallel. Under cold exposure or beta 3-agonist treatment, a specific up-regulation of GLUT4 expression was observed in interscapular brown adipose tissue. The regional difference described in this study, could participate in preferential fat-pad growth under physiological conditions as well as in pathological situations.

Adipose Tissue↗
PubMed1993

Local sympathetic denervation of white adipose tissue in rats induces preadipocyte proliferation without noticeable changes in metabolism.

The direct influence of the sympathetic nervous system on white adipose tissue was studied by performing a unilateral surgical denervation of the retroperitoneal fat pad in rats, the contralateral pad being used as a control. One week after surgery, the weight of the denervated pad was significantly higher than that of the intact pad. In vivo, glucose utilization was not altered by denervation. The expression of GLUT4 as well as the expression and activity of fatty acid synthase, lipoprotein lipase, and hormone-sensitive triglyceride lipase were similar in the two pads. Lipolysis in response to norepinephrine, determined in vitro, was not modified by denervation although the ratio between alpha 2- and beta-adrenergic receptors was changed. Denervation induced an increase in DNA content without change in the number of mature adipocytes. The expression of A2COL6/pOb24, a marker of the early step of adipocyte differentiation, was significantly enhanced in the denervated pad, suggesting an increased number of preadipocytes. This was confirmed by an increased cell number observed in the denervated fat pad 1 month after surgery. In conclusion, surgical denervation of the white fat pad does not alter the glucose and lipid metabolisms. By contrast, it accelerated adipocyte differentiation and led to the recruitment of new precursors.

Adipose Tissue↗
PubMed1992

Molecular and metabolic changes in white adipose tissue of the rat during development of ventromedial hypothalamic obesity.

We have previously shown that rats made obese by lesion of ventromedial hypothalamus (VMH) nuclei, demonstrate an hyper-responsiveness to insulin with regard to whole-body glucose utilization one week after injury. This is mainly due to an increased glucose uptake in white adipose tissue. Six weeks after the lesion, glucose utilization in white adipose tissue returns to normal values. These modifications in insulin responsiveness could be mediated by altered activity and/or concentration of intracellular insulin effectors. In this study, we have measured the expression of the insulin-sensitive glucose transporter, Glut 4 and the activities and expression of key lipogenic enzymes (fatty-acid synthase and acetyl-CoA carboxylase) in white adipose tissue, one and six weeks after the lesion. All these parameters, as well as glucose transport and metabolism determined in white adipocytes, were markedly increased one week after the lesion. They returned to control values within six weeks in VMH-lesioned rats. These results indicate the existence of an increased expression of Glut 4 and lipogenic enzymes in white adipose tissue of VMH-lesioned rats which decreased with time and were parallel to glucose utilization determined in vivo.

Adipose Tissue↗
PubMed1992

Insulin receptor kinase activity in muscles and white adipose tissue during course of VMH obesity.

Early after lesion of the ventromedial hypothalamus nuclei (VMH), insulin-induced glucose utilization is increased in white adipose tissue (WAT), whereas oxidative and glycolytic muscles are, respectively, normoresponsive or resistant to insulin. Five weeks later, all of the muscles are resistant, whereas WAT returns to normal responsiveness. The aim of this study was to characterize the insulin receptor kinase activity in WAT and muscles 1 and 6 wk after lesion. The number and affinity of insulin receptors were not modified in any of the tissues studied. Autophosphorylation and phosphorylation of an exogenous substrate were similar in oxidative and glycolytic muscles of VMH and control rats both 1 and 6 wk after the lesion. Insulin receptors from WAT of 1-wk VMH rats exhibited a 2.5-fold increase in insulin-stimulated autophosphorylation and phosphorylation. Six weeks after the lesion, both autophosphorylation and phosphorylation returned to normal values. This suggests that insulin receptor tyrosine kinase activity does not play a significant role in the insulin resistance of skeletal muscles but has a crucial role in mediating the variations of insulin action on WAT observed during the development of VMH obesity.

Adipose Tissue↗
PubMed1992

Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization.

Brown adipocytes are thermogenic cells which play an important role in energy balance. Their thermogenic activity is due to the presence of a mitochondrial uncoupling protein (UCP). Until recently, it was admitted that in rodents brown adipocytes were mainly located in classical brown adipose tissue (BAT). In the present study, we have investigated the presence of UCP protein or mRNA in white adipose tissue (WAT) of rats. Using polymerase chain reaction or Northern blot hybridization, UCP mRNA was detected in mesenteric, epidydimal, retroperitoneal, inguinal and particularly in periovarian adipose depots. The uncoupling protein was detected by Western blotting in mitochondria from periovarian adipose tissue. When rats were submitted to cold or to treatment with a beta-adrenoceptor agonist, UCP expression was increased in this tissue as in typical brown fat. Moreover, the expression was decreased in obese fa/fa rats compared to lean controls. Morphological studies showed that periovarian adipose tissue of rats kept at 24 degrees C contained cells with numerous typical BAT mitochondria with or without multilocular lipid droplets. Immunocytochemistry confirmed that multilocular cells expressed mitochondrial UCP. Furthermore, the number of brown adipocytes and the density of mitochondrial cristae increased in parallel with exposure to cold. These results demonstrate that adipocytes expressing UCP are present in adipose deposits considered as white fat. They suggest the existence of a continuum in rodents between BAT and WAT, and a great plasticity between adipose tissue phenotypes. The physiological importance of brown adipocytes in WAT and the regulation of UCP expression remain open questions.

Adipose Tissue↗