Journal ArticleDOI
What the Genetics of Lipodystrophy Can Teach Us About Insulin Resistance and Diabetes
Camille Vatier,Guillaume Bidault,Guillaume Bidault,Nolwenn Briand,Nolwenn Briand,Anne-Claire Guénantin,Anne-Claire Guénantin,Laurence Teyssières,Laurence Teyssières,Olivier Lascols,Jacqueline Capeau,Corinne Vigouroux +11 more
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TLDR
The reduced expandability of AT alters its ability to buffer excess caloric intake, leading to ectopic lipid storage that impairs insulin signaling and other cellular functions (“lipotoxicity”) and the close relationships between ageing, inflammatory processes, lipodystrophy, and IR are pointed out.Abstract:
Genetic lipodystrophic syndromes are rare diseases characterized by generalized or partial fat atrophy (lipoatrophy) associated with severe metabolic complications such as insulin resistance (IR), diabetes, dyslipidemia, nonalcoholic fatty liver disease, and ovarian hyperandrogenism. During the last 15 years, mutations in several genes have been shown to be responsible for monogenic forms of lipodystrophic syndromes, of autosomal dominant or recessive transmission. Although the molecular basis of lipodystrophies is heterogeneous, most mutated genes lead to impaired adipogenesis, adipocyte lipid storage, and/or formation or maintenance of the adipocyte lipid droplet (LD), showing that primary alterations of adipose tissue (AT) can result in severe systemic metabolic and endocrine consequences. The reduced expandability of AT alters its ability to buffer excess caloric intake, leading to ectopic lipid storage that impairs insulin signaling and other cellular functions (“lipotoxicity”). Genetic studies have also pointed out the close relationships between ageing, inflammatory processes, lipodystrophy, and IR.read more
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Journal ArticleDOI
Serum Adiponectin and Leptin Levels in Patients with Lipodystrophies
TL;DR: Serum adiponectin and leptin levels are extremely low in patients with generalized lipodystrophies and may be related to severe insulin resistance and its metabolic complications in lipodyStrophies.
Journal ArticleDOI
POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies
TL;DR: An overview of critical Polδ activities in the context of pathologic conditions is provided, showingPolδ has been shown to be important for multiple forms of DNA repair, including nucleotide excision repair, double strand break repair, base excision Repair, and mismatch repair.
Journal ArticleDOI
On the formation of lipid droplets in human adipocytes: the organization of the perilipin-vimentin cortex.
Hans Heid,Steffen Rickelt,Ralf Zimbelmann,Stefanie Winter,Heiderose Schumacher,Yvette Dörflinger,Caecilia Kuhn,Werner W. Franke +7 more
TL;DR: A novel pathway for the LD formation is presented and discussed and multiple sheaths of smooth endoplasmic reticulum cisternae surrounding concentrically nascent LDs are shown.
Journal ArticleDOI
One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes.
Camille Vatier,Camille Vatier,Camille Vatier,Sabrina Fetita,Philippe Boudou,C. Tchankou,L. Deville,J.P. Riveline,Jacques Young,L. Mathivon,F. Travert,D. Morin,J. Cahen,O. Lascols,F. Andreelli,Yves Reznik,E. Mongeois,I. Madelaine,Mc. Vantyghem,J.F. Gautier,J.F. Gautier,Corinne Vigouroux +21 more
TL;DR: Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies, and the increase in disposition index was related to a decrease in percentage of total and trunk body fat.
Journal ArticleDOI
A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy.
Damien Galant,Bénédicte Gaborit,Camille Desgrouas,I. Abdesselam,Monique Bernard,Nicolas Lévy,Françoise Merono,Catherine Coirault,Patrice Roll,Arnaud Lagarde,Nathalie Bonello-Palot,Patrice Bourgeois,Anne Dutour,Catherine Badens +13 more
TL;DR: It is shown that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24, and the causative link between mutation and phenotype cannot be formally established.
References
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