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Biomedical subjects

Bruno Fève

Publications and source records attributed to Bruno Fève.

10 recordsLinked to original sources
PubMed2006

Carotid arterial stiffness, elastic fibre network and vasoreactivity in semicarbazide-sensitive amine-oxidase null mouse.

OBJECTIVE: We examined the arterial phenotype of semicarbazide-sensitive amine-oxidase null mouse (SSAO -/-) using various techniques including high resolution echotracking. METHODS AND RESULTS: SSAO -/- mice showed no change in arterial pressure under anesthesia. The in vivo arterial diameter, only measured in the carotid artery (CA), was higher in SSAO -/- than in SSAO +/+ animals. Elastic modulus-wall stress curves and CA rupture pressure were similar between SSAO -/- and +/+ mice, indicating no change in arterial wall stiffness or mechanical strength. There was no significant difference in insoluble elastin, total collagen content and elastic lamellar morphology between the two genotypes. No alteration in vascular reactivity was observed in aortic rings and mesenteric arteries from SSAO -/- mice. Aortic lysyl oxidase (LO) activity remained unaltered, indicating that SSAO invalidation is not accompanied by a compensatory increase in LO activity. CONCLUSION: This is the first functional study of arteries lacking SSAO. Our results indicate that SSAO -/- mice present an increased arterial diameter associated with normal arterial mechanical properties, suggesting that SSAO deficiency might contribute to arterial wall remodeling. However, these results argue against the hypothesis that SSAO intervenes in elastic fibre organization, elastin cross-linking processes and vasoreactivity.

Amine Oxidase (Copper-Containing)↗
PubMed2006

[Relationship between obesity, inflammation and insulin resistance: new concepts].

White adipose tissue is the main site of energy storage, but it is now recognized as an active participant in regulating physiologic and pathologic processes including immunity and inflammation. It has an endocrine function by secreting at least two main hormones, leptin and adiponectin. It can secrete other products, named adipokines, including cytokines and chemokines, involved in inflammation process. The release of adipokines by either adipocytes or adipose tissue infiltrated macrophages lead to a chronic sub-inflammatory state that could play a central role in cardiovascular complications linked to obesity and insulin resistance, a risk factor to develop type-2 diabetes.

Animals↗
PubMed2005

Adipogenesis: cellular and molecular aspects.

Obesity and lipoatrophy are major risks for insulin resistance, non-insulin-dependent diabetes and cardiovascular disease. In the past three decades, significant advances have been made in delineating the key transcription factors of adipogenesis, as well as extracellular effectors and intracellular signalling pathways that regulate fat cell formation. This review focuses on in vitro models of adipocyte differentiation, and on the balance between pro- and anti-adipogenic factors that drive the adipocyte differentiation process. Full understanding of the mechanisms of adipose tissue differentiation represents a major issue to develop a comprehensive strategy to prevent and treat obesity.

Adipocytes↗
PubMed2005

Type A insulin resistance syndrome revealing a novel lamin A mutation.

Particular forms of polycystic ovary syndrome with severe hyperandrogenism, acanthosis nigricans, and marked insulin resistance, defining the type A insulin resistance syndrome, are due to insulin receptor gene mutations. However, the majority of affected individuals do not have such mutation, arguing for the genetic heterogeneity of this syndrome. The familial partial lipodystrophy of the Dunnigan type, one of the diseases due to mutations in the lamin A/C (LMNA) gene, is characterized by a lipodystrophic phenotype and shares some clinical and metabolic features with the type A syndrome. We describe here the case of a nonobese 24-year-old woman affected with type A syndrome without clinical lipodystrophy. We linked this phenotype to a novel heterozygous missense mutation in the LMNA, predicting a G602S amino acid substitution in lamin A. This mutation cosegregated with impaired glucose tolerance, insulin resistance, and acanthosis nigricans in the absence of clinical lipodystrophy in the family. The skin fibroblasts from the proband exhibited nuclear alterations similar to those described in other laminopathies, and showed several defects in the insulin transduction pathway. This study further extends the vast range of diseases linked to LMNA mutations and identifies another genetic cause for the type A insulin resistance syndrome.

Adult↗
PubMed2004

In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes.

A serious metabolic syndrome combining insulin-resistance, dyslipidemia, central adiposity, and peripheral lipoatrophy has arisen in HIV-infected patients receiving highly active antiretroviral therapy. The aim of this work was to examine the effects of the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz on adipocyte differentiation and metabolism. When induced to differentiate in the presence of efavirenz (5-50 microm), 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol droplets. This phenomenon was rapidly reversible and was also readily detectable in the 3T3-L1 preadipose cell line and in primary cultures of human preadipocytes. When applied to mature 3T3-F442A adipocytes, efavirenz induced a delayed and moderate reduction in cell triglyceride content. Measurement of [(3)H]deoxyglucose uptake, basal and agonist-stimulated lipolysis, and cell viability indicated that these pathways are not involved in efavirenz effects on triacylglycerol accumulation. By contrast, we found that the NNRTI induced a dramatic dose- and time-dependent decrease in gene and protein expression of the lipogenic transcription factor sterol regulatory element-binding protein-1c (SREBP-1c). Adipose conversion was only altered at the highest efavirenz concentrations, as suggested by the mild reduction in peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer-binding protein-alpha. CCAAT/enhancer-binding protein-beta remained unchanged. The inhibition of SREBP-1c expression was accompanied by a sharp reduction in the expression of SREBP-1c target genes and in the adipocyte lipogenic activity in efavirenz-treated cells. Finally, the inhibitory effect of efavirenz on cell triglyceride accumulation was prevented by directly providing free fatty acids to the cells and was reversed by overexpression of a dominant positive form of SREBP-1c, reinforcing the implication of this transcription factor in the antilipogenic effect of the drug. When considered together, these results demonstrate for the first time that the NNRTI efavirenz induces a strong inhibition of the SREBP-1c-dependent lipogenic pathway that might contribute to adipose tissue atrophy.

3T3 Cells↗
PubMed2004

Semicarbazide-sensitive amine oxidase in annulo-aortic ectasia disease: relation to elastic lamellae-associated proteins.

Lysyl oxidases (Lox), which are members of the amine oxidase family, are involved in the maturation of elastic lamellae and collagen fibers. Modifications of amine oxidases in idiopathic annulo-aortic ectasia disease (IAAED) have never been investigated. Our aim was to examine the expression of several proteins that might interfere with elastic fiber organization in control (n=10) and IAAED (n=18) aortic tissues obtained at surgery. Expression of amine oxidases and semicarbazide-sensitive amine oxidase (SSAO), and cellular phenotypic markers were examined by immunohistopathology and confocal microscopy. The expression of these proteins was assessed in relation to clinical and histomorphological features of the arterial wall. In control aorta, SSAO staining was expressed along elastic lamellae, whereas in aneurysmal areas of IAAED, SSAO was markedly decreased, in association with severe disorganization of elastic lamellae. Smooth muscle myosin heavy chain was also decreased in IAAED compared with controls, indicating smooth muscle cell dedifferentiation. Multiple regression analysis showed that elastic lamellar thickness (ELT) was correlated positively with the SSAO:elastin ratio and negatively with the Lox:elastin ratio, and that the clinical features of IAAED (aneurysm, thoracic aorta diameter, and aortic insufficiency) were positively correlated with ELT but not with SSAO. The relationship between SSAO expression and ELT suggests that this amine oxidase may be involved in elastic fiber organization. However, in advanced IAAED, the deficit in SSAO expression could be secondary to the decrease and fragmentation of elastic fibers and/or to vascular smooth muscle cell dedifferentiation.

Amine Oxidase (Copper-Containing)↗
PubMed2003

Regulation of semicarbazide-sensitive amine oxidase expression by tumor necrosis factor-alpha in adipocytes: functional consequences on glucose transport.

Membrane-associated semicarbazide-sensitive amine oxidase (SSAO) is mainly present in the media of aorta and in adipose tissue. Recent works have reported that SSAO activation can stimulate glucose transport of fat cells and promote adipose conversion. In this study, the murine 3T3-L1 preadipose cell line was used to investigate SSAO regulation by tumor necrosis factor-alpha (TNF-alpha), a cytokine that is synthesized in fat cells and known to be involved in obesity-linked insulin resistance. SSAO mRNA and protein levels, and enzyme activity were decreased by TNF-alpha in a dose- and time-dependent manner, without any change of SSAO affinity for substrates or inhibitors. SSAO inhibition caused by TNF-alpha was spontaneously reversed along the time after TNF-alpha removal. The decrease in SSAO expression also occurred in white adipose tissue of C57BL/6 mice treated with mTNF-alpha. Overall, we demonstrated that reduction in SSAO expression induced by the cytokine had marked repercussions on amine-stimulated glucose transport, in a dose- and time-dependent manner. This effect was more pronounced than the inhibiting effect of TNF-alpha on insulin-stimulated glucose transport. Moreover, the peroxisome proliferator-activated receptor gamma agonists thiazolidinediones did not reverse either TNF-alpha effect on amine-sensitive glucose transport or the inhibition of SSAO activity, whereas they antagonized TNF-alpha effects on insulin-sensitive glucose transport. These results demonstrate that TNF-alpha can strongly down-regulate SSAO expression and activity, and through this mechanism can dramatically reduce amine-stimulated glucose transport. This suggests a potential role of this regulatory process in the pathogenesis of glucose homeostasis dysregulations observed during diseases accompanied by TNF-alpha overproduction, such as cachexia or obesity.

3T3 Cells↗
PubMed2002

The extreme C terminus of rat liver carnitine palmitoyltransferase I is not involved in malonyl-CoA sensitivity but in initial protein folding.

We previously reported that the N-terminal domain (1-147 residues) of rat liver carnitine palmitoyltransferase I (L-CPTI) was essential for import into the outer mitochondrial membrane and for maintenance of a malonyl-CoA-sensitive conformation. Malonyl-CoA binding experiments using mitochondria of Saccharomyces cerevisiae strains expressing wild-type L-CPTI or previously constructed chimeric CPTs (Cohen, I., Kohl, C., McGarry, J.D., Girard, J., and Prip-Buus, C. (1998) J. Biol. Chem. 273, 29896-29904) indicated that the N-terminal domain was unable, independently of the C-terminal domain, to bind malonyl-CoA with a high affinity, suggesting that the modulation of malonyl-CoA sensitivity occurred through N/C intramolecular interactions. To assess the role of the C terminus in malonyl-CoA sensitivity, a series of C-terminal deletion mutants was generated. The kinetic properties of Delta772-773 and Delta767-773 deletion mutants were similar to those of L-CPTI, indicating that the last two highly conserved Lys residues in all known L-CPTI species were not functionally essential. By contrast, Delta743-773 deletion mutant was totally inactive and unfolded, as shown by its sensitivity to trypsin proteolysis. Because the C terminus of the native folded L-CPTI could be cleaved by trypsin without inducing protein unfolding, we concluded that the last 31 C-terminal residues constitute a secondary structural determinant essential for the initial protein folding of L-CPTI.

Amino Acid Sequence↗