Dataset Information

Epidermal Acyl-CoA-binding protein is indispensable for systemic energy homeostasis.

ABSTRACT:

Objectives

The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously found that loss of acyl-CoA-binding protein (ACBP) in keratinocytes upregulates lipolysis in white adipose tissue and alters hepatic lipid metabolism, suggesting a link between epidermal barrier functions and systemic energy metabolism.

Methods

To assess the physiological responses to loss of ACBP in keratinocytes in detail, we used full-body ACBP^-/- and skin-specific ACBP^-/- knockout mice to clarify how loss of ACBP affects 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). To further elucidate the role of the epidermal barrier in systemic energy metabolism, we included mice with defects in skin structural proteins (ma/ma Flg^ft/ft) in these studies.

Results

We show that the ACBP^-/- mice and skin-specific ACBP^-/- knockout mice exhibited increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, was reversed by housing the mice at thermoneutrality (30 °C) or pharmacological ?-adrenergic blocking. Interestingly, these findings were phenocopied in flaky tail mice (ma/ma Flg^ft/ft). Taken together, we demonstrate that a compromised epidermal barrier induces a ?-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature.

Conclusions

Our findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis. Thus, regulation of epidermal barrier functions warrants further attention to understand the regulation of systemic metabolism in further detail.

SUBMITTER: Neess D

PROVIDER: S-EPMC7797911 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Epidermal Acyl-CoA-binding protein is indispensable for systemic energy homeostasis.

Neess Ditte D Kruse Vibeke V Marcher Ann-Britt AB Wæde Mie Rye MR Vistisen Julie J Møller Pauline M PM Petersen Rikke R Brewer Jonathan R JR Ma Tao T Colleluori Georgia G Severi Ilenia I Cinti Saverio S Gerhart-Hines Zach Z Mandrup Susanne S Færgeman Nils J NJ

Molecular metabolism 20201218

<h4>Objectives</h4>The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously found that loss of acyl-CoA-binding protein (ACBP) in keratinocytes upregulates lipolysis in white adipose tissue and alters hepatic lipid metabolism, suggesting a link be ...[more]

PMID: 33346070

Similar Datasets

Project description:BACKGROUND:Lipid metabolism is pivotal for the growth of apicomplexan parasites. Lipid synthesis requires bulk carbon skeleton acyl-CoAs, the transport of which depends on the acyl-CoA binding protein (ACBP). In Neospora caninum, the causative agent of neosporosis, the FASII pathway is required for growth and pathogenicity. However, little is known about the fatty acid transport mechanism in N. caninum. METHODS:We have identified a cytosolic acyl-CoA binding protein, with highly conserved amino acid residues and a typical acyl-CoA binding domain in N. caninum. The recombinant NcACBP protein was expressed to verify the binding activities of NcACBP in vitro, and the heterologous expression of NcACBP in ?acbp yeast in vivo. Lipid extraction from ?NcACBP or the wild-type of N. caninum was analyzed by GC-MS or TLC. Furthermore, transcriptome analysis was performed to compare the gene expression in different strains. RESULTS:The NcACBP recombinant protein was able to specifically bind acyl-CoA esters in vitro. A yeast complementation assay showed that heterologous expression of NcACBP rescued the phenotypic defects in ?acbp yeast, indicating of the binding activity of NcACBP in vivo. The disruption of NcACBP did not perturb the parasite's growth but enhanced its pathogenicity in mice. The lipidomic analysis showed that disruption of NcACBP caused no obvious changes in the overall abundance and turnover of fatty acids while knockout resulted in the accumulation of triacylglycerol. Transcriptional analysis of ACBP-deficient parasites revealed differentially expressed genes involved in a wide range of biological processes such as lipid metabolism, posttranslational modification, and membrane biogenesis. CONCLUSIONS:Our study demonstrated that genetic ablation of NcACBP did not impair the survival and growth phenotype of N. caninum but enhanced its pathogenicity in mice. This deletion did not affect the overall fatty acid composition but modified the abundance of TAG. The loss of NcACBP resulted in global changes in the expression of multiple genes. This study provides a foundation for elucidating the molecular mechanism of lipid metabolism in N. caninum.

Dataset Information

Epidermal Acyl-CoA-binding protein is indispensable for systemic energy homeostasis.

Objectives

Methods

Results

Conclusions

Publications

Epidermal Acyl-CoA-binding protein is indispensable for systemic energy homeostasis.

Similar Datasets

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