Age-Related Lipid Metabolic Signature in Human<i>LMNA</i>-Lipodystrophic Stem Cell-Derived Adipocytes

Sánchez, Patricia; Infante, Arantza; Eguino, Garbiñe Ruiz de; Fuentes-Maestre, Jorge; García‐Verdugo, José Manuel; Rodrı́guez, Clara I.

doi:10.1210/jc.2014-4528

Cited by 12 publications

(11 citation statements)

References 39 publications

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“…Accumulation of LMNA in hMSCs determines a premature aging phenotype that ultimately reduces the functionality of these cells 27 . LMNA accumulation in hMSCs deranges lipid metabolism and leads to structural and functional alterations of mitochondria and of the endoplasmic reticulum, which are organelles important for lipid homeostasis 28 . These alterations have been reported in such lipid-related metabolic diseases as obesity and type 2 diabetes 29 .…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, exposure to an obesogenic environment in utero is associated with proteome alterations in hA-MSCs. The proteins deranged are involved in the stress response, cytoskeleton and metabolic pathways, which are often associated with obesity-related phenotypes 10 11 25 28 . The possible role of these protein alterations in enhancing susceptibility to obesity or to obesity-related disorders in newborns of obese mothers requires further investigations.…”

Section: Discussionmentioning

confidence: 99%

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Proteome analysis of human amniotic mesenchymal stem cells (hA-MSCs) reveals impaired antioxidant ability, cytoskeleton and metabolic functionality in maternal obesity

Capobianco

Caterino

Iaffaldano

et al. 2016

Sci Rep

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Maternal obesity increases the risk of obesity and/or obesity-related diseases in the offspring of animal models. The aim of this study was to identify metabolic dysfunctions that could represent an enhanced risk for human obesity or obesity-related diseases in newborn or in adult life, similar to what occurs in animal models. To this aim, we studied the proteome of 12 obese (Ob-) and 6 non-obese (Co-) human amniotic mesenchymal stem cells (hA-MSCs) obtained from women at delivery by cesarean section (pre-pregnancy body mass index [mean ± SD]: 42.7 ± 7.7 and 21.3 ± 3.3 kg/m2, respectively). The proteome, investigated by two-dimensional fluorescence difference gel electrophoresis/mass spectrometry, revealed 62 differently expressed proteins in Ob- vs Co-hA-MSCs (P < 0.05), nine of which were confirmed by western blotting. Bioinformatics analysis showed that these 62 proteins are involved in several statistically significant pathways (P < 0.05), including the stress response, cytoskeleton and metabolic pathways. Oxidative stress was shown to be an early triggering factor of tissue fat accumulation and obesity-related disorders in the offspring of obese animal models. Our finding of a reduced stress response in Ob-hA-MSCs suggests that a similar mechanism could occur also in humans. Long-term follow-up studies of newborns of obese mothers are required to verify this hypothesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteome analysis of human amniotic mesenchymal stem cells (hA-MSCs) reveals impaired antioxidant ability, cytoskeleton and metabolic functionality in maternal obesity

Capobianco

Caterino

Iaffaldano

et al. 2016

Sci Rep

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“…Both animal and in vitro human cell culture models of progeroid laminopathies have successfully recapitulated the aging phenotypes that patients exhibit [ 45 – 48 ]. Interestingly, in vitro human cell models of HGPS have shown an increased differentiation of MSCs towards the osteoblastic lineage (increased alkaline phosphatase activity, an early marker of osteogenesis in MSCs [ 3 ], and increased expression of osteogenic genes), reflecting a “premature” osteogenesis in vitro [ 49 , 50 ].…”

Section: Msc Osteogenic Differentiation In Health and Agingmentioning

confidence: 99%

Osteogenesis and aging: lessons from mesenchymal stem cells

2018

Self Cite

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Aging is a high risk factor for the development of osteoporosis, a multifactorial age-related progressive disease characterized by reduced bone mass and increased risk of fractures. At the cellular level, the mesenchymal stem cell pool in the bone marrow niche shows a biased differentiation into adipogenesis at the cost of osteogenesis. This differentiation shift leads to decreased bone formation, contributing to the etiology of osteoporosis. This review will focus on the most recent/relevant molecular findings driving this functional impairment of mesenchymal stem cells in the aging process.

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“…Interestingly, HGPS patients also develop lipodystrophy and prelamin A accumulation affects human mesenchymal stem cell-derived adipocytes, leading to smaller lipid droplets, increased lipolysis, alteration in the structure of the endoplasmic reticulum, partial depolarization of mitochondria membranes and alteration of the lipid profile. 48,49 …”

Section: The Nuclear Lamina and Metabolismmentioning

confidence: 99%

The nuclear lamina in health and disease

Dobrzynska

Gonzalo

Shanahan

et al. 2016

Nucleus

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The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases.

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Age-Related Lipid Metabolic Signature in HumanLMNA-Lipodystrophic Stem Cell-Derived Adipocytes

Abstract: Prelamin A accumulation causes mitochondrial dysfunction, endoplasmic reticulum stress, and altered lipid metabolism resembling a premature aging phenotype.

Cited by 12 publications

References 39 publications

Proteome analysis of human amniotic mesenchymal stem cells (hA-MSCs) reveals impaired antioxidant ability, cytoskeleton and metabolic functionality in maternal obesity

Proteome analysis of human amniotic mesenchymal stem cells (hA-MSCs) reveals impaired antioxidant ability, cytoskeleton and metabolic functionality in maternal obesity

Osteogenesis and aging: lessons from mesenchymal stem cells

The nuclear lamina in health and disease

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