Irisin levels in LMNA-associated partial lipodystrophies

Bensmaine, Faiza; Benomar, Kanza; Espiard, Stéphanie; Vahé, Claire; Mapihan, Kristell Le; Lion, Georges; Lemdani, Mohamed; Chazard, Emmanuel; Ernst, Olivier; Vigouroux, Corinne; Pigny, Pascal; Vantyghem, Marie-Christine

doi:10.1016/j.diabet.2018.08.003

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…FPLD syndromes are rare disorders of variable lipoatrophy in certain body regions and normal or excess adiposity in others [1], [2], [3], [4], [5]. By far, the most common lipodystrophy is antiretroviral-induced lipodystrophy in HIV patients [2], [6].…”

Section: Discussionmentioning

confidence: 99%

Massive labial lipomatous hypertrophy in familial partial lipodystrophy seen on computed tomographic angiography

Selting

Hansen

Harrison

2019

Radiology Case Reports

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We present a 28-year-old female with a rare familial partial lipodystrophy. Originally presenting at the age of 14, she began experiencing hypertrophy of the fat in the mons pubis and labia majora regions. By the age of 24 she had disfiguring hypertrophy of these areas with severe fatty overgrowth, similar in nature to that experienced by her father and paternal grandmother. During her workup and planning for suction lipectomy, she underwent computed tomography angiography with the imaging manifestation of severe massive subcutaneous fat hypertrophy; the imaging appearance was only able to be explained after a thorough review of the patient's history and medical literature.

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Section: Discussionmentioning

confidence: 99%

Massive labial lipomatous hypertrophy in familial partial lipodystrophy seen on computed tomographic angiography

Selting

Hansen

Harrison

2019

Radiology Case Reports

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“…The muscle cells and adipocytes in FLPD2 exhibit features of a diabetes-related metabolic disorder, including loss of body fat, glucose intolerance, high blood pressure, high plasma triglyceride, low HDL cholesterol levels, and loss of insulin sensitivity. 233 The causes of this lipotoxic metabolic stress in FPLD2 are attributed to several cellular pathways, namely impaired adipocyte differentiation (represented by lower expression of PPAR-γ2, GLUT4, and higher phosphorylation of AKT1), 234 lower production of leptins 233 and retinol-binding proteins (RBPs), 235 higher expression of irisin, 236 and deregulated transport of free fatty acids to different cells. 237 The diabetic phenotype in FLPD2 results from the differential response to dietary insulin signaling.…”

Section: Metabolic Stress and Diabetesmentioning

confidence: 99%

Nuclear proteostasis imbalance in laminopathy‐associated premature aging diseases

Pande

Ghosh

2023

The FASEB Journal

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Laminopathies are a group of rare genetic disorders with heterogeneous clinical phenotypes such as premature aging, cardiomyopathy, lipodystrophy, muscular dystrophy, microcephaly, epilepsy, and so on. The cellular phenomena associated with laminopathy invariably show disruption of nucleoskeleton of lamina due to deregulated expression, localization, function, and interaction of mutant lamin proteins. Impaired spatial and temporal tethering of lamin proteins to the lamina or nucleoplasmic aggregation of lamins are the primary molecular events that can trigger nuclear proteotoxicity by modulating differential protein–protein interactions, sequestering quality control proteins, and initiating a cascade of abnormal post‐translational modifications. Clearly, laminopathic cells exhibit moderate to high nuclear proteotoxicity, raising the question of whether an imbalance in nuclear proteostasis is involved in laminopathic diseases, particularly in diseases of early aging such as HGPS and laminopathy‐associated premature aging. Here, we review nuclear proteostasis and its deregulation in the context of lamin proteins and laminopathies.

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“…The irisin level in the FPLD group displayed an increasing trend. The irisin/leptin ratio was significantly enhanced compared with HC and OND (Figure 1) [2]. Consequently, the disruption of irisin dimers can be pursued as an appealing strategy to counteract the overactivation of irisin function in subjects with LD.…”

Section: Lipodystrophymentioning

confidence: 99%

“…Among the first aspects to be considered are the amount and distribution of fat mass. On one side of this great gap, there is obesity and more complex levels of metabolic syndrome, presenting as excessive white fat deposits; on the other, there is lipodystrophy (LD), characterized instead by an abnormal loss of white and subcutaneous adipose tissue [1,2].…”

Section: Introductionmentioning

confidence: 99%

Disruption of Irisin Dimerization by FDA-Approved Drugs: A Computational Repurposing Approach for the Potential Treatment of Lipodystrophy Syndromes

Flori

Brogi

Sirous

et al. 2023

IJMS

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In this paper, we present the development of a computer-based repurposing approach to identify FDA-approved drugs that are potentially able to interfere with irisin dimerization. It has been established that altered levels of irisin dimers are a pure hallmark of lipodystrophy (LD) syndromes. Accordingly, the identification of compounds capable of slowing down or precluding the irisin dimers’ formation could represent a valuable therapeutic strategy in LD. Combining several computational techniques, we identified five FDA-approved drugs with satisfactory computational scores (iohexol, XP score = −7.70 kcal/mol, SP score = −5.5 kcal/mol, ΔGbind = −61.47 kcal/mol, ΔGbind (average) = −60.71 kcal/mol; paromomycin, XP score = −7.23 kcal/mol, SP score = −6.18 kcal/mol, ΔGbind = −50.14 kcal/mol, ΔGbind (average) = −49.13 kcal/mol; zoledronate, XP score = −6.33 kcal/mol, SP score = −5.53 kcal/mol, ΔGbind = −32.38 kcal/mol, ΔGbind (average) = −29.42 kcal/mol; setmelanotide, XP score = −6.10 kcal/mol, SP score = −7.24 kcal/mol, ΔGbind = −56.87 kcal/mol, ΔGbind (average) = −62.41 kcal/mol; and theophylline, XP score = −5.17 kcal/mol, SP score = −5.55 kcal/mol, ΔGbind = −33.25 kcal/mol, ΔGbind (average) = −35.29 kcal/mol) that are potentially able to disrupt the dimerization of irisin. For this reason, they deserve further investigation to characterize them as irisin disruptors. Remarkably, the identification of drugs targeting this process can offer novel therapeutic opportunities for the treatment of LD. Furthermore, the identified drugs could provide a starting point for a repositioning approach, synthesizing novel analogs with improved efficacy and selectivity against the irisin dimerization process.

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Irisin levels in LMNA-associated partial lipodystrophies

Cited by 6 publications

References 41 publications

Massive labial lipomatous hypertrophy in familial partial lipodystrophy seen on computed tomographic angiography

Massive labial lipomatous hypertrophy in familial partial lipodystrophy seen on computed tomographic angiography

Nuclear proteostasis imbalance in laminopathy‐associated premature aging diseases

Disruption of Irisin Dimerization by FDA-Approved Drugs: A Computational Repurposing Approach for the Potential Treatment of Lipodystrophy Syndromes

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