Compromised epidermal barrier stimulates Harderian gland activity and hypertrophy in ACBP−/− mice

Bek, Signe; Neess, Ditte; Dixen, Karen; Bloksgaard, Maria; Marcher, Ann-Britt; Chemnitz, J.; Færgeman, Nils J.; Mandrup, Susanne

doi:10.1194/jlr.m060780

Cited by 7 publications

(2 citation statements)

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“…We have previously shown that ablation of ACBP in the skin diminishes very long-chain fatty acid levels in the stratum corneum, which are required for epidermal barrier function [10]. As a consequence of this, the sebaceous as well as the Harderian glands become hyperplastic and produce abnormal high levels of lipids, which are believed to be secreted to provide further insulation ( [13] and our unpublished results). The present findings show that ACBP -/and K14-ACBP -/mice in addition upregulate their energy expenditure to defend their body temperature when housed at room temperature.…”

Section: Discussionmentioning

confidence: 75%

“…Since transepidermal water loss (TEWL) is significantly increased in both full-body ACBP -/and K14-ACBP -/mice [13], we speculated that the increased energy expenditure in these mouse models is caused by the impaired epidermal barrier. To investigate this, we took advantage of another mouse model, the flaky tail mice (ma/ma Flg ft/ft ), which carry a frameshift mutation in the filaggrin gene and a mutation in the Tmem79 gene (matted, ma).…”

Section: Acbp In Keratinocytes Is Indispensable For Normal Systemic Ementioning

confidence: 99%

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The Epidermal Barrier is Indispensable for Systemic Energy Homeostasis

Neess

Kruse

Marcher

et al. 2020

Preprint

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ObjectivesHomeostatic regulation of body temperature is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and neuronal regulators. Although the skin is the largest sensory organ of the human body, and plays a fundamental role in regulating body temperature, it is surprising that adaptive alterations in skin functions and morphology only vaguely have been associated with physiological responses to cold stress or sensation of ambient temperatures.MethodsTo unravel the physiological responses to a compromised epidermal barrier in detail we have used animal models with either defects in skin lipid metabolism (ACBP-/- and skin-specific ACBP-/- knockout mice) or defects in skin structural proteins (ma/ma Flgft/ft). The primary objective was to clarify how defects in epidermal barrier function affect 1) energy expenditure by indirect calorimetry, 2) response to high fat feeding and a high oral glucose load and 3) expression of brown-selective gene programs by quantitative PCR in inguinal WAT (iWAT).ResultsWe show that mice with a compromised epidermal barrier function exhibit increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, is reversed by housing the mice at thermoneutrality (30°C) or by pharmacological β-adrenergic blocking. These findings show that a compromised epidermal barrier induces a β-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature.ConclusionOur findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis.HighlightsEnergy expenditure is significantly augmented in mice with impaired epidermal barrier.Mice with compromised barrier display increased food intake while maintaining normal bodyweight.Mice with an impaired epidermal barrier are resistant to diet-induced obesity and insulin resistance.Compromised barrier function induces expression of brown-selective gene programs in iWAT.Thermoneutral housing or blocking β-adrenergic signaling prevents induction of brite-selective genes in iWAT and reverses food intake.

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Section: Discussionmentioning

confidence: 75%

Section: Acbp In Keratinocytes Is Indispensable For Normal Systemic Ementioning

confidence: 99%

The Epidermal Barrier is Indispensable for Systemic Energy Homeostasis

Neess

Kruse

Marcher

et al. 2020

Preprint

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Genetically modified laboratory mice with sebaceous glands abnormalities

Ehrmann¹,

Schneider²

2016

Cell. Mol. Life Sci.

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Sebaceous glands (SG) are exocrine glands that release their product by holocrine secretion, meaning that the whole cell becomes a secretion following disruption of the membrane. SG may be found in association with a hair follicle, forming the pilosebaceous unit, or as modified SG at different body sites such as the eyelids (Meibomian glands) or the preputial glands. Depending on their location, SG fulfill a number of functions, including protection of the skin and fur, thermoregulation, formation of the tear lipid film, and pheromone-based communication. Accordingly, SG abnormalities are associated with several diseases such as acne, cicatricial alopecia, and dry eye disease. An increasing number of genetically modified laboratory mouse lines develop SG abnormalities, and their study may provide important clues regarding the molecular pathways regulating SG development, physiology, and pathology. Here, we summarize in tabulated form the available mouse lines with SG abnormalities and, focusing on selected examples, discuss the insights they provide into SG biology and pathology. We hope this survey will become a helpful information source for researchers with a primary interest in SG but also as for researchers from unrelated fields that are unexpectedly confronted with a SG phenotype in newly generated mouse lines.

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