ALOX5AP overexpression in adipose tissue leads to LXA<inf>4</inf> production and protection against diet-induced obesity and insulin resistance

Ivet Elias, Tura Ferré, Laia Vilà, Sergio Muñoz, Alba Casellas, Miquel Garcia, Maria Molas, Judith Agudo, Carles Roca, Jesús Ruberte, Fatima Bosch, Sylvie Franckhauser

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

Abstract

© 2016 by the American Diabetes Association. Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation and insulin resistance, LXA4 may exert anti-inflammatory effects and alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase-activating protein (ALOX5AP), are involved. ALOX5 and ALOX5AP expression is increased in humans and rodents with obesity and insulin resistance. We found that transgenicmice overexpressing ALOX5AP in adipose tissue had higher LXA4 rather than higher LTB4 levels, were leaner, and showed increased energy expenditure, partly due to browning of white adipose tissue (WAT). Upregulation of hepatic LXR and Cyp7a1 led to higher bile acid synthesis, which may have contributed to increased thermogenesis. In addition, transgenic mice were protected against dietinduced obesity, insulin resistance, and inflammation. Finally, treatment of C57BL/6J mice with LXA4, which showed browning of WAT, strongly suggests that LXA4 is responsible for the transgenic mice phenotype. Thus, our data support that LXA4 may hold great potential for the future development of therapeutic strategies for obesity and related diseases.
Original languageEnglish
Pages (from-to)2139-2150
JournalDiabetes
Volume65
Issue number8
DOIs
Publication statusPublished - 1 Aug 2016

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