A new therapeutic approach to treat psoriasis by inhibition of fatty acid oxidation by Etomoxir

Caspary, F.; Elliott, Graham R.; Navé, Barbara T.; Verzaal, Perry; Rohrbach, Martin; Das, Pranab Kumar; Nagelkerken, Lex; Nieland, John D.

doi:10.1111/j.1365-2133.2005.06811.x

Cited by 25 publications

(28 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional evidence for the importance of fatty acid metabolism in the skin is the increased activity of the fatty acid enzyme CPT1 in psoriasis. Blocking CPT1 activity, key for b-oxidation, reduces keratinocyte differentiation and proliferation in psoriatic skin (Caspary et al 2005). These findings support a role for fatty acid metabolism in fueling cellular processes in the skin and its appendages.…”

Section: Potential Additional Roles Of Adipocytes In the Skinsupporting

confidence: 58%

Adipocytes in Skin Health and Disease

Rivera-Gonzalez

Shook

Horsley

2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

Adipocytes are intimately associated with the dermal compartment of the skin, existing in a specialized dermal depot and displaying dynamic changes in size during tissue homeostasis. However, the roles of adipocytes in cutaneous biology and disease are not well understood. Traditionally, adipocytes within tissues were thought to act as reservoirs of energy, as thermal, or as structural support. In this review, we discuss recent studies revealing the cellular basis of the dynamic development and regenerative capacity of dermal adipocytes associated with the hair cycle and following injury. We discuss and speculate on potential roles of dermal adipocytes in cutaneous biology with an emphasis on communication during hair follicle growth and wound healing. Finally, we explore how alterations in the dermal adipose tissue may support clinical manifestations of cutaneous diseases such as lipodystrophy, obesity, and alopecia. ADIPOCYTE DEVELOPMENT AND HOMEOSTASIS IN THE SKIN

show abstract

Section: Potential Additional Roles Of Adipocytes In the Skinsupporting

confidence: 58%

Adipocytes in Skin Health and Disease

Rivera-Gonzalez

Shook

Horsley

2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

show abstract

“…It has also been suggested that epidermal fatty acid-binding protein contributes to the pathogenesis of psoriasis through activation of the NF-kB signalling pathway 63 , a powerful transcriptional regulator of pro-inflammatory genes. Furthermore, etomoxir-mediated b-oxidation inhibition is beneficial in the treatment of psoriasis 64 . We provide a mechanistic link connecting enhanced fatty acid b-oxidation within epidermal cells to their immune function that acts to direct leukocyte recruitment.…”

Section: Discussionmentioning

confidence: 99%

Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production

et al. 2014

View full text Add to dashboard Cite

In addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. To date, such cell-intrinsic metabolic-immunologic cross-talk has only been described operating in cells of the immune system. Here we show that epidermal cells utilize fatty acid b-oxidation to fuel their contribution to the immune response during cutaneous inflammation. By live imaging metabolic and immunological processes within intact zebrafish embryos during cutaneous inflammation, we uncover a mechanism where elevated b-oxidation-fuelled mitochondria-derived reactive oxygen species within epidermal cells helps guide matrix metalloproteinase-driven leukocyte recruitment. This mechanism requires the activity of a zebrafish homologue of the mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the first example of metabolic reprogramming operating within a non-immune cell type to help control its contribution to the immune response. Targeting of this metabolic-immunologic interface within keratinocytes may prove useful in treating inflammatory dermatoses.

show abstract

“…Etomoxir has been shown to irreversibly inhibit the activity of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme of FAO ( Fig. 1 ), in primary human fi broblasts ( 40 ). In our experiments, pretreatment of cells with etomoxir resulted in a concentrationdependent reduction of the abundance of FAO metabolites directly derived from enzymatic conversions within the palmitate ␤ -oxidation ( Fig.…”

Section: Application Potential Of the Assaymentioning

confidence: 66%

In situ assay of fatty acid β-oxidation by metabolite profiling following permeabilization of cell membranes

Ensenauer

Fingerhut

Schriever

et al. 2012

Journal of Lipid Research

View full text Add to dashboard Cite

The mitochondrial FA ␤ -oxidation (FAO) pathway is a major contributor to cellular energy production and homeostasis, particularly once glycogen stores are depleted owing to fasting ( 1 ). Substantial amounts of energy are provided by FAO for heart, skeletal muscle, and liver function. In monogenetic defi ciencies of FAO or the carnitine shuttle system, accumulation of acyl-CoA intermediates and depletion of energy and free carnitine occur, specifically at times of increased energy demands, including fever and impaired food supply ( 2 ). Altered FA catabolism is considered key in the development of obesity-induced insulin resistance, because cellular overload with long-chain FAs is thought to exert a disastrous effect on mitochondrial function ( 3, 4 ). Cytoprotective mechanisms against FA lipotoxicity include channelling of FAs into triglyceride pools and enhancement of FA degradation via mitochondrial ␤ -oxidation ( 4 ).Thus, quantitative analysis of FAO has become increasingly important in assessing lipid-induced metabolic impairment and evaluating potential pharmacologic strategies designed to improve ␤ -oxidation fl ux ( 4 ). The most commonly applied method to assess functional FAO in cellular models has been the analysis of total FAO fl ux following incubation of intact cells with 14 C-or 3 H-labeled

show abstract

A new therapeutic approach to treat psoriasis by inhibition of fatty acid oxidation by Etomoxir

Abstract: We conclude that fatty acid metabolism and in particular CPT-1 may be an excellent target for treatment of psoriasis.

Cited by 25 publications

References 23 publications

Adipocytes in Skin Health and Disease

Adipocytes in Skin Health and Disease

Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production

In situ assay of fatty acid β-oxidation by metabolite profiling following permeabilization of cell membranes

Contact Info

Product

Resources

About