Fat in the skin

Radner, Franz P.W.; Grond, Susanne; Haemmerle, Guenter; Lass, Achim; Zechner, Rudolf

doi:10.4161/derm.3.2.15472

Cited by 25 publications

(9 citation statements)

References 97 publications

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“…The increased numbers of lipid droplets in the stratum corneum are likely due to impaired hydrolysis of triglycerides, a process that is essential for the formation of acylceramides and the epidermal water barrier ( Elias et al , 2008 ). A similar accumulation of neutral lipid droplets in the stratum corneum is found in neutral lipid storage disease due to CGI-58 deficiency ( Demerjian et al , 2006 ), where triglyceride hydrolysis is clearly impaired ( Radner et al , 2011 ; Radner et al , 2010 ; Ujihara et al , 2010 ). We did not find reduced transcript levels for CGI-58, ATGL, triglyceride hydrolase K, or triglyceride hydrolase N in paw skin of Slurp1 −/− mice (not shown).…”

Section: Discussionsupporting

confidence: 53%

Palmoplantar Keratoderma along with Neuromuscular and Metabolic Phenotypes in Slurp1 -Deficient Mice

Adeyo

Allan²,

Barnes

et al. 2014

Journal of Investigative Dermatology

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Mutations in SLURP1 cause mal de Meleda, a rare palmoplantar keratoderma (PPK). SLURP1 is a secreted protein that is expressed highly in keratinocytes but has also been identified elsewhere (e.g., spinal cord neurons). Here, we examined Slurp1-deficient mice (Slurp1−/−) created by replacing exon 2 with β-gal and neo cassettes. Slurp1−/− mice developed severe PPK characterized by increased keratinocyte proliferation, an accumulation of lipid droplets in the stratum corneum, and a water barrier defect. In addition, Slurp1−/− mice exhibited reduced adiposity, protection from obesity on a high-fat diet, low plasma lipid levels, and a neuromuscular abnormality (hind limb clasping). Initially, it was unclear whether the metabolic and neuromuscular phenotypes were due to Slurp1 deficiency because we found that the targeted Slurp1 mutation reduced the expression of several neighboring genes (e.g., Slurp2, Lypd2). We therefore created a new line of knockout mice (Slurp1X−/− mice) with a simple nonsense mutation in exon 2. The Slurp1X mutation did not reduce the expression of adjacent genes, but Slurp1X−/− mice exhibited all of the phenotypes observed in the original line of knockout mice. Thus, Slurp1 deficiency in mice elicits metabolic and neuromuscular abnormalities in addition to PPK.

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Section: Discussionsupporting

confidence: 53%

Palmoplantar Keratoderma along with Neuromuscular and Metabolic Phenotypes in Slurp1 -Deficient Mice

Adeyo

Allan²,

Barnes

et al. 2014

Journal of Investigative Dermatology

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“…The presence of lactic acid generated by sweat (>99 µg/ml) [15] and of a sugar, such as sialic acid, common to humans and animals justifies the predominance of respective catabolic genes in our skin metagenome datasets. Similarly, the detection of a high proportion of sequences related to triacylglycerol catabolism, a skin lipid critically involved in epidermal permeability, suggests its utilization as a carbon source and triacylglycerol catabolism could also provide a significant contribution to the lipases produced by the skin for preventing lipid accumulation as in the ichthyosis pathology [16].…”

Section: Resultsmentioning

confidence: 99%

Life on Human Surfaces: Skin Metagenomics

et al. 2013

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The human skin microbiome could provide another example, after the gut, of the strong positive or negative impact that human colonizing bacteria can have on health. Deciphering functional diversity and dynamics within human skin microbial communities is critical for understanding their involvement and for developing the appropriate substances for improving or correcting their action. We present a direct PCR-free high throughput sequencing approach to unravel the human skin microbiota specificities through metagenomic dataset analysis and inter-environmental comparison. The approach provided access to the functions carried out by dominant skin colonizing taxa, including Corynebacterium, Staphylococcus and Propionibacterium, revealing their specific capabilities to interact with and exploit compounds from the human skin. These functions, which clearly illustrate the unique life style of the skin microbial communities, stand as invaluable investigation targets for understanding and potentially modifying bacterial interactions with the human host with the objective of increasing health and well being.

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“…Defects in lipid metabolism in the skin often result in ichthyosis and a defective skin barrier (30)(31)(32). For example, CGI-58 (comparative gene identification 58) deficiency impairs triglyceride hydrolysis in the skin, leading to an accumulation of neutral lipid droplets in the stratum corneum, a skin barrier defect, and ichthyosis (33,34).…”

Section: Lmnb2mentioning

confidence: 99%

An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

Jung

Tatar

et al. 2014

Molecular and Cellular Biology

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d B-type lamins (lamins B1 and B2) have been considered to be essential for many crucial functions in the cell nucleus (e.g., DNA replication and mitotic spindle formation). However, this view has been challenged by the observation that an absence of both B-type lamins in keratinocytes had no effect on cell proliferation or the development of skin and hair. The latter findings raised the possibility that the functions of B-type lamins are subserved by lamins A and C. To explore that idea, we created mice lacking all nuclear lamins in keratinocytes. Those mice developed ichthyosis and a skin barrier defect, which led to death from dehydration within a few days after birth. Microscopy of nuclear-lamin-deficient skin revealed hyperkeratosis and a disordered stratum corneum with an accumulation of neutral lipid droplets; however, BrdU incorporation into keratinocytes was normal. Skin grafting experiments confirmed the stratum corneum abnormalities and normal BrdU uptake. Interestingly, the absence of nuclear lamins in keratinocytes resulted in an interspersion of nuclear/endoplasmic reticulum membranes with the chromatin. Thus, a key function of the nuclear lamina is to serve as a "fence" and prevent the incursion of cytoplasmic organelles into the nuclear chromatin.T he B-type lamins, which are expressed in virtually all cells from the earliest stages of development, have been assumed to play vital functions in the cell nucleus (1-8). Multiple studies contributed to this view. One group found lamin B at sites of DNA replication during S-phase and suggested that it was important for DNA replication (1). Disruption of nuclear lamin organization with a dominant negative lamin B mutant in Xenopus egg extracts inhibited DNA replication (2, 3), mitotic spindle assembly (4), and nuclear envelope assembly in interphase (5). An RNA interference (RNAi) knockdown of lamin B1 and lamin B2 was reported to lead to mitotic arrest and apoptosis (6). Other studies reported that B-type lamins were important for chromatin organization and proper gene expression (7,8).The view that B-type lamins play crucial roles in the cell nucleus likely dampened enthusiasm for testing the importance of B-type lamins in knockout mice. Ultimately, however, Yang et al. (9) created conditional knockout alleles for both Lmnb1 and Lmnb2 and used those alleles to generate keratinocyte-specific Lmnb1 Lmnb2 knockout mice. Remarkably, a complete absence of both lamin B1 and lamin B2 in keratinocytes had no discernible effect on cell growth or the complex developmental programs involved in the formation of the epidermis, hair, and nails. By electron microscopy, the nuclear envelope and heterochromatin distribution appeared normal in Lmnb1 Lmnb2-deficient keratinocytes (9). Similarly, hepatocyte-specific Lmnb1 Lmnb2 knockout mice had normal liver histology and normal liver function tests (10). These studies cast doubt on the notion that B-type lamins are essential for DNA replication and mitosis but did not exclude the possibility that these functions were si...

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Fat in the skin

Cited by 25 publications

References 97 publications

Palmoplantar Keratoderma along with Neuromuscular and Metabolic Phenotypes in Slurp1 -Deficient Mice

Palmoplantar Keratoderma along with Neuromuscular and Metabolic Phenotypes in Slurp1 -Deficient Mice

Life on Human Surfaces: Skin Metagenomics

An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

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