The Significance of Epidermal Lipid Metabolism in Whole-Body Physiology

Kruse, Vibeke; Neess, Ditte; Færgeman, Nils J.

doi:10.1016/j.tem.2017.06.001

Cited by 38 publications

(30 citation statements)

References 94 publications

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“…For both desaturases, we found high desaturase activity in intestinal tissues, as well as detectable desaturase activity in the epidermis and the germ line, but not in muscle tissues. Lipid metabolism in the epidermis has recently been recognized as influencing systemside physiological responses (Kruse et al 2017). Thus C. elegans fatty acid desaturation efficiency in skin cells could influence barrier formation and cuticle development.…”

Section: Discussionmentioning

confidence: 99%

New strains for tissue-specific RNAi studies in Caenorhabditis elegans

Watts

Harrison

Omi

et al. 2018

Preprint

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RNA interference is a powerful tool for dissecting gene function. In Caenorhabditis elegans, ingestion of double stranded RNA causes strong, systemic knockdown of target genes. Further insight into gene function can be revealed by tissue-specific RNAi techniques. Currently available tissue-specific C. elegans strains rely on rescue of RNAi function in a desired tissue or cell in an otherwise RNAi deficient genetic background. In a classroom setting, we attempted to assess the contribution of specific tissues to polyunsaturated fatty acid (PUFA) synthesis using currently available tissue-specific RNAi strains. We discovered that rde-1 (ne219), a commonly used RNAi-resistant mutant strain, retains considerable RNAi capacity against RNAi directed at PUFA synthesis genes. Using GC/MS, we measured changes in the fatty acid products of the desaturase enzymes that synthesize PUFAs in a gene dosage sensitive manner.With this method, we tested a panel of previously described RNAi-deficient mutant strains, and found that almost all of them retained a certain degree of RNAi capacity. Importantly, we found that the before mentioned strain, rde-1 (ne219) and the reported germline only RNAi strain, rrf-1 (pk1417) are not appropriate genetic backgrounds for tissue-specific RNAi experiments.However, the knockout mutant rde-1 (ne300) was strongly resistant to dsRNA induced RNAi, and may be appropriate for construction of robust tissue-specific RNAi strains.

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Section: Discussionmentioning

confidence: 99%

New strains for tissue-specific RNAi studies in Caenorhabditis elegans

Watts

Harrison

Omi

et al. 2018

Preprint

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“…In purple module (R = -0.2 and Bonferroni-corrected P = 4.4E-03), ‘skin/tissue development’, ‘lipid metabolic process’, and ‘regulation of water loss via skin’ were found ( Figure 4A ). Lipid metabolism and prevention of water loss are known to have roles in skin barrier function and often influenced by aging [ 35 , 36 ]. Genes involved in lipid metabolism such as ERBB3 , LIPK , LIPN , SGPL1 , and SMPD3 were decreased with aging as well as several water loss regulation genes including ABCA12 , CLDN1 , FLG , FLG2 , and GBA ( Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis

Cho

Seo

2018

Aging

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There are various factors that alter physiological characteristics in skin. Elucidating the underlying mechanism of transcriptional alterations by intrinsic and extrinsic factors may lead us to understand the aging process of skin. To identify the transcriptomic changes of the aging skin, we analyzed publicly available RNA sequencing data from Genotype-Tissue Expression (GTEx) project. GTEx provided RNA sequencing data of suprapubic (n=228) and lower leg (n=349) skins, which are photo-protected and photo–damaged. Using differentially expressed gene analysis and weighted gene co-expression network analysis, we characterized transcriptomic changes due to UV exposure and aging. Genes involved in skin development such as epidermal differentiation complex component (SPRR and LCE families), vasculature development (TGFBR1, TGFBR2, TGFBR3, KDR, FGF2, and VEGFC), and matrix metalloproteinase (MMP2, MMP3, MMP8, MMP10, and MMP13) were up-regulated by UV exposure. Also, down-regulated lipid metabolism and mitochondrial biogenesis were observed in photo-damaged skin. Moreover, wound healing process was universally down-regulated in suprapubic and lower leg with aging and further down-regulation of lipid metabolism and up-regulation of vasculature development were found as photo-aging signatures. In this study, dynamic transcriptomic alterations were observed in aged skin. Hence, our findings may help to discover a potential therapeutic target for skin rejuvenation.

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“…Thus dWAT thickens in mice housed at room temperature (sub-thermoneutral); mice that are unable to develop thicker dWAT are chronically cold stressed (18). Importantly, several mouse strains with defects of skin lipogenic enzymes lose heat at high rates; interestingly, these strains are also resistant to diet-induced obesity (26)(27)(28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Contrasting recruitment of skin-associated adipose depots during cold challenge of mouse and human

Kasza

Kuehn

Völzke

et al. 2020

Preprint

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Mammalian skin impacts metabolic efficiency system-wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding function and regulation. For human, we distinguish skin-associated fat (SAF) as the body-wide depot and characterize it separately from the subcutaneous fat pads characteristic of abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6-fold) in women than men, and highly subject-specific. We used molecular and cellular assays of β-adrenergic induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body-wide human SAF depot becomes lipolytic, generating heat in response to β-adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), the thickness of dWAT increases, whereas β-adrenergic stimulation reduces the size of human skin-associated adipocytes. We summarize the regulation of the skin-associated adipocytes by age, sex, and adiposity, for both species, and conclude that overall, a combination of subcutaneous and dermal adipose tissues in mouse contributes the same way to maintaining body temperature as human SAF.

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The Significance of Epidermal Lipid Metabolism in Whole-Body Physiology

Cited by 38 publications

References 94 publications

New strains for tissue-specific RNAi studies in Caenorhabditis elegans

New strains for tissue-specific RNAi studies in Caenorhabditis elegans

Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis

Contrasting recruitment of skin-associated adipose depots during cold challenge of mouse and human

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