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Article

Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls

1
Aix Marseille Université, INSERM, MMG, 13005 Marseille, France
2
Aix Marseille Université, Laboratoire de Chimie Analytique, Faculté de Pharmacie, 13005 Marseille, France
3
Aix Marseille Université, INSERM, INRAE, C2VN, 13005 Marseille, France
4
APHM, Endocrinology, Metabolic diseases and nutrition department, 13005 Marseille, France
5
APHM, Hôpital de la Timone, Laboratoire de Génétique Moléculaire, 13005 Marseille, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(2), 310; https://doi.org/10.3390/cells9020310
Received: 18 November 2019 / Revised: 20 January 2020 / Accepted: 25 January 2020 / Published: 28 January 2020
(This article belongs to the Collection Lamins and Laminopathies)
This study details the clinical and cellular phenotypes associated with two missense heterozygous mutations in LMNA, c.1745G>T p.(Arg582Leu), and c.1892G>A p.(Gly631Asp), in two patients with early onset of diabetes mellitus, hypertriglyceridemia and non-alcoholic fatty liver disease. In these two patients, subcutaneous adipose tissue was persistent, at least on the abdomen, and the serum leptin level remained in the normal range. Cellular studies showed elevated nuclear anomalies, an accelerated senescence rate and a decrease of replication capacity in patient cells. In cellular models, the overexpression of mutated prelamin A phenocopied misshapen nuclei, while the partial reduction of lamin A expression in patient cells significantly improved nuclear morphology. Altogether, these results suggest a link between lamin A mutant expression and senescence associated phenotypes. Transcriptome analysis of the whole subcutaneous adipose tissue from the two patients and three controls, paired for age and sex using RNA sequencing, showed the up regulation of genes implicated in immunity and the down regulation of genes involved in development and cell differentiation in patient adipose tissue. Therefore, our results suggest that some mutations in LMNA are associated with severe metabolic phenotypes without subcutaneous lipoatrophy, and are associated with nuclear misshaping. View Full-Text
Keywords: dyslipidemia; metabolic syndrome; insulin resistance; lamin A/C; nuclear anomalies and premature senescence dyslipidemia; metabolic syndrome; insulin resistance; lamin A/C; nuclear anomalies and premature senescence
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MDPI and ACS Style

Desgrouas, C.; Varlet, A.-A.; Dutour, A.; Galant, D.; Merono, F.; Bonello-Palot, N.; Bourgeois, P.; Lasbleiz, A.; Petitjean, C.; Ancel, P.; Levy, N.; Badens, C.; Gaborit, B. Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls. Cells 2020, 9, 310. https://doi.org/10.3390/cells9020310

AMA Style

Desgrouas C, Varlet A-A, Dutour A, Galant D, Merono F, Bonello-Palot N, Bourgeois P, Lasbleiz A, Petitjean C, Ancel P, Levy N, Badens C, Gaborit B. Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls. Cells. 2020; 9(2):310. https://doi.org/10.3390/cells9020310

Chicago/Turabian Style

Desgrouas, Camille; Varlet, Alice-Anaïs; Dutour, Anne; Galant, Damien; Merono, Françoise; Bonello-Palot, Nathalie; Bourgeois, Patrice; Lasbleiz, Adèle; Petitjean, Cathy; Ancel, Patricia; Levy, Nicolas; Badens, Catherine; Gaborit, Bénédicte. 2020. "Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls" Cells 9, no. 2: 310. https://doi.org/10.3390/cells9020310

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