Fat in the skin

Keratinocyte differentiation is essential for skin development and the formation of the skin permeability barrier. This process involves an orchestrated remodelling of lipids. The cleavage of precursor lipids from lamellar bodies by β-glucocerebrosidase, sphingomyelinase, phospholipases, and sterol sulfatase generates ceramides, non-esterified fatty acids (FAs), and cholesterol for the lipid-containing extracellular matrix, the lamellar membranes in the stratum corneum. The importance of triacylglycerol (TAG) hydrolysis for the formation of a functional permeability barrier was only recently appreciated. Mice with defects in TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2-knock-out) or TAG catabolism (comparative gene identification-58, – CGI-58-knock-out) develop severe permeability barrier defects and die soon after birth because of desiccation. In humans, mutations in the CGI-58 gene also cause (non-lethal) neutral lipid storage disease with ichthyosis (NLSDI). As a result of defective TAG synthesis or catabolism, humans and mice lack ω-(O)-acylceramides, which are essential lipid precursors for the formation of the corneocyte lipid envelope. This structure plays an important role in linking the lipid-enriched lamellar membranes to highly cross-linked corneocyte proteins. This review focuses on the current knowledge of biochemical mechanisms that are essential for epidermal neutral lipid metabolism and the formation of a functional skin permeability barrier.

• Publication year

  2011

• Venue

  Dermato-Endocrinology

• Publication date

  2011-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4161/derm.3.2.15472PMID 21695016PMCID 3117006
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores

  2011cited by this paper
• Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene.

  2010cited by this paper
• Molecular analysis of Chanarin-Dorfman syndrome (CDS) patients: Identification of novel mutations in the ABHD5 gene.

  2010cited by this paper
• A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles.

  2010cited by this paper
• Clinical and genetic characterization of chanarin-dorfman syndrome patients: first report of large deletions in the ABHD5 gene

  2010cited by this paper
• The N-terminal Region of Comparative Gene Identification-58 (CGI-58) Is Important for Lipid Droplet Binding and Activation of Adipose Triglyceride Lipase*

  2010cited by this paper
• CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase

  2010cited by this paper
• Liver cirrhosis in an infant with Chanarin–Dorfman syndrome caused by a novel splice‐site mutation in ABHD5

  2010cited by this paper
• Epithelial and Mesenchymal Cell Biology CGI-58 Is an /-Hydrolase within Lipid Transporting Lamellar Granules of Differentiated Keratinocytes

  2010cited by this paper
• Neutral lipid storage leads to acylceramide deficiency, likely contributing to the pathogenesis of Dorfman-Chanarin syndrome.

  2010cited by this paper
• Epidermal triglyceride levels are correlated with severity of ichthyosis in Dorfman-Chanarin syndrome.

  2010cited by this paper
• Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5.

  2009cited by this paper
• Growth Retardation, Impaired Triacylglycerol Catabolism, Hepatic Steatosis, and Lethal Skin Barrier Defect in Mice Lacking Comparative Gene Identification-58 (CGI-58)*

  2009cited by this paper
• The skin's barrier.

  2009cited by this paper
• The familial occurrence of fat containing vacuoles in the leukocytes diagnosed in two brothers suffering from dystrophia musculorum progressiva (ERB.).

  2009cited by this paper
• Fate of fat: the role of adipose triglyceride lipase in lipolysis.

  2009cited by this paper
• Omega-O-acylceramide, a lipid essential for mammalian survival.

  2008cited by this paper
• CGI-58, the Causative Gene for Chanarin-Dorfman Syndrome, Mediates Acylation of Lysophosphatidic Acid*

  2008cited by this paper
• Severe steatohepatitis in a patient with a rare neutral lipid storage disorder due to ABHD5 mutation.

  2008cited by this paper
• Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy.

  2008cited by this paper
• Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology Published, JLR Papers in Press, January 8, 2008.

  2008cited by this paper
• Clinical and genetic characterization of Chanarin-Dorfman syndrome.

  2008cited by this paper
• Distal lipid storage myopathy due to PNPLA2 mutation.

  2008cited by this paper
• Chanarin–Dorfman syndrome caused by a novel splice site mutation in ABHD5

  2008cited by this paper
• Triglyceride deposit cardiomyovasculopathy.

  2008cited by this paper
• The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets.

  2008cited by this paper
• Regulation and function of triacylglycerol lipases in cellular metabolism.

  2008cited by this paper
• The skin: an indispensable barrier

  2008cited by this paper
• A novel S115G mutation of CGI-58 in a Turkish patient with Dorfman-Chanarin syndrome.

  2007cited by this paper
• Thematic review series: Skin Lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis Published, JLR Papers in Press, September 13, 2007.

  2007cited by this paper
• An idea whose time has gone

  2007cited by this paper
• Large-scale identification of human genes implicated in epidermal barrier function

  2007cited by this paper
• Characterization of liver X receptor expression and function in human skin and the pilosebaceous unit

  2007cited by this paper
• The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy

  2007cited by this paper
• Novel duplication mutation in the patatin domain of adipose triglyceride lipase (PNPLA2) in neutral lipid storage disease with severe myopathy

  2007cited by this paper
• A comparative study of human GS2, its paralogues, and its rat orthologue.

  2007cited by this paper
• CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation Published, JLR Papers in Press, February 17, 2007.

  2007cited by this paper
• Defective Lipolysis and Altered Energy Metabolism in Mice Lacking Adipose Triglyceride Lipase

  2006cited by this paper
• The Saccharomyces cerevisiae Lipin Homolog Is a Mg2+-dependent Phosphatidate Phosphatase Enzyme*♦

  2006cited by this paper
• Barrier dysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome).

  2006cited by this paper
• Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.

  2006cited by this paper
• Biochemistry of Human Stratum Corneum Lipids

  2005cited by this paper
• The cornified envelope: a model of cell death in the skin

  2005cited by this paper
• Erythrokeratoderma variabilis‐like ichthyosis in Chanarin–Dorfman syndrome

  2005cited by this paper
• Two new mutations of the ABHD5 gene in a new adult case of Chanarin Dorfman syndrome: an uncommon lipid storage disease.

  2005cited by this paper
• The Epidermal Lamellar Body as a Multifunctional Secretory Organelle

  2005cited by this paper
• Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase.

  2005cited by this paper
• Lipopenia and Skin Barrier Abnormalities in DGAT2-deficient Mice*

  2004cited by this paper
• Steatohepatitis and unsuspected micronodular cirrhosis in Dorfman-Chanarin syndrome with documented ABHD5 mutation.

  2004cited by this paper
• Perilipin A Mediates the Reversible Binding of CGI-58 to Lipid Droplets in 3T3-L1 Adipocytes*

  2004cited by this paper
• CGI-58 Interacts with Perilipin and Is Localized to Lipid Droplets

  2004cited by this paper
• Biosynthesis of acylceramide in murine epidermis: characterization by inhibition of glucosylation and deglucosylation, and by substrate specificity.

  2004cited by this paper
• Truncation of CGI-58 protein causes malformation of lamellar granules resulting in ichthyosis in Dorfman-Chanarin syndrome.

  2003cited by this paper
• Barrier function of the skin: "la raison d'être" of the epidermis.

  2003cited by this paper
• Epithelial barrier function: assembly and structural features of the cornified cell envelope.

  2002cited by this paper
• The ω-hydroxyceramides of pig epidermis are attached to corneocytes solely through ω-hydroxyl groups

  2001cited by this paper
• Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin

  2001cited by this paper
• Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.

  2001cited by this paper
• The omega-hydroxyceramides of pig epidermis are attached to corneocytes solely through omega-hydroxyl groups.

  2001cited by this paper
• Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity.

  2001cited by this paper
• Permeability barrier disorder in Niemann-Pick disease: sphingomyelin-ceramide processing required for normal barrier homeostasis.

  2000cited by this paper
• Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function.

  2000cited by this paper
• Oxysterols induce differentiation in human keratinocytes and increase Ap-1-dependent involucrin transcription.

  2000cited by this paper
• Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.

  2000cited by this paper
• Lipids and barrier function of the skin.

  2000cited by this paper
• Bricks and mortar of the epidermal barrier

  1999cited by this paper
• Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier.

  1999cited by this paper
• Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha.

  1998cited by this paper
• Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes.

  1998cited by this paper
• Neutral lipid storage disease: a genetic disorder with abnormalities in the regulation of phospholipid metabolism.

  1998cited by this paper
• Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing

  1998cited by this paper
• Expression of retinoid-X receptors (-alpha,-beta,-gamma) and retinoic acid receptors (-alpha,-beta,-gamma) in normal human skin: an immunohistological evaluation.

  1997cited by this paper
• Neutral lipid storage disease with fatty liver and cholestasis.

  1997cited by this paper
• Expression of retinoid-X receptors (-· ,-· ,-·) and retinoic acid receptors (-· ,-· ,-·) in normal human skin: an immunohistological evaluation

  1997cited by this paper
• Secretory phospholipase A2 activity is required for permeability barrier homeostasis.

  1996cited by this paper
• Acylglycerol Recycling from Triacylglycerol to Phospholipid, Not Lipase Activity, Is Defective in Neutral Lipid Storage Disease Fibroblasts*

  1996cited by this paper
• The Turnover of Cytoplasmic Triacylglycerols in Human Fibroblasts Involves Two Separate Acyl Chain Length-dependent Degradation Pathways (*)

  1995cited by this paper
• Extracellular processing of phospholipids is required for permeability barrier homeostasis.

  1995cited by this paper
• Permeability barrier requirements regulate epidermal beta-glucocerebrosidase.

  1994cited by this paper
• Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

  1994cited by this paper
• Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.

  1993cited by this paper
• Molecular biology of the skin : the keratinocyte

  1993cited by this paper
• 4 – The Cornified Envelope: A Key Structure of Terminally Differentiating Keratinocytes

  1993cited by this paper
• La raison d'être

  1992cited by this paper
• Ichthyosis: Mechanisms of Disease

  1992cited by this paper
• Epidermal lipids.

  1992cited by this paper
• Neutral lipid storage disease: a possible functional defect in phospholipid- linked triacylglycerol metabolism.

  1991cited by this paper
• Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids.

  1991cited by this paper
• Metabolism of linoleic acid in porcine epidermis.

  1990cited by this paper
• Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

  1990cited by this paper
• Independence of triacylglycerol‐containing compartments in cultured fibroblasts from Wolman disease and multisystemic lipid storage myopathy

  1989cited by this paper
• Neutral lipid storage disease with ichthyosis: Lipid content and metabolism of fibroblasts

  1988cited by this paper
• Epidermal lipids

  1987cited by this paper
• Metabolism of neutral lipids in cultured fibroblasts from multisystemic (or type 3) lipid storage myopathy.

  1987cited by this paper
• Metabolism of 1-pyrenedecanoic acid and accumulation of neutral fluorescent lipids in cultured fibroblasts of multisystemic lipid storage myopathy.

  1987cited by this paper
• Cytochemical and biochemical localization of lipase and sphingomyelinase activity in mammalian epidermis.

  1986cited by this paper
• Lamellar body-enriched fractions from neonatal mice: preparative techniques and partial characterization.

  1985cited by this paper
• Neutral lipid storage disease with ichthyosis. Defective lamellar body contents and intracellular dispersion.

  1985cited by this paper
• Lipid composition and acid hydrolase content of lamellar granules of fetal rat epidermis.

  1985cited by this paper
• Sphingolipids of the stratum corneum and lamellar granules of fetal rat epidermis.

  1984cited by this paper

• Dietary lipids are largely deposited in skin and rapidly affect insulating properties

  2025cites this paper
• Therapeutic Benefits of Topical Omega‐3 Polyunsaturated Fatty Acids in Skin Diseases and Cosmetics: An Updated Systematic Review

  2025cites this paper
• Holobiont Rebalancing by a Natural Gentian Extract on a Skin Dehydration Model

  2024cites this paper
• Dietary lipid is largely deposited in skin and rapidly affects insulating properties

  2024cites this paper
• Role of the ABCA4 Gene Expression in the Clearance of Toxic Vitamin A Derivatives in Human Hair Follicle Stem Cells and Keratinocytes

  2023cites this paper
• The PNPLA family of enzymes: characterisation and biological role

  2023cites this paper
• HPLC Method for Separation of Cannabidiol Hemp Seed Oil with Skin Lipids and Tandem HRMS Technology for Characterization of a Chemical Marker

  2021cites this paper
• Prediction of neonatal acne based on maternal lipidomic profiling

  2020cites this paper
• Lipid storage myopathies: Current treatments and future directions.

  2018cites this paper
• The Significance of Epidermal Lipid Metabolism in Whole-Body Physiology.

  2017cites this paper
• Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

  2017cites this paper
• Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation

  2016cites this paper
• Lipin-1 expression is critical for keratinocyte differentiation[S]

  2016cites this paper
• OsHSD1, a hydroxysteroid dehydrogenase, is involved in cuticle formation and lipid homeostasis in rice.

  2016cites this paper
• Lipid signaling in keratinocytes: Lipin-1 plays a PArt1

  2016cites this paper
• Ceramide synthesis in the epidermis.

  2014cites this paper
• CGI-58, a key regulator of lipid homeostasis and signaling in plants, also regulates polyamine metabolism

  2014cites this paper
• Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice

  2014cites this paper
• Role of lipids in the formation and maintenance of the cutaneous permeability barrier.

  2014cites this paper
• The future of skin metagenomics.

  2014cites this paper
• 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

  2014cites this paper
• The sheep genome illuminates biology of the rumen and lipid metabolism

  2014cites this paper
• From Blood Smear to Lipid Disorder: A Case Report

  2013cites this paper
• Life on Human Surfaces: Skin Metagenomics

  2013cites this paper
• The α/β Hydrolase CGI-58 and Peroxisomal Transport Protein PXA1 Coregulate Lipid Homeostasis and Signaling in Arabidopsis[W]

  2013cites this paper
• Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58[S]

  2012cites this paper
• Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man Biogenesis and functions of lipid droplets in plants

  2012cites this paper