Abstract
Lysophosphatidic acid (LPA) is a bioactive phospholipid that activates cell proliferation, differentiation and migration via the activation of its membrane-bound receptors (LPAR 1 to 6) expressed in various tissues and organs. Adipose tissue produces LPA, which, in turn, increases preadipocyte proliferation, mainly through the stimulation of LPA1R. However, while LPA plasma levels increase with obesity, only few studies have investigated the acute autocrine properties of LPA on mature adipocytes. We therefore assessed the lipolytic and antilipolytic effects of LPA on human adipocytes. Here, we show that, in human subcutaneous adipocytes, LPA (0.1–10 µM) did not mimic insulin effects in human adipocytes, i.e. lipolysis inhibition and glucose uptake activation. By contrast, supramicromolar doses of the phospholipid slightly activated lipolysis, and the effect of 100 µM LPA was additive to the β-adrenergic stimulation of lipolysis by isoprenaline. Moreover, LPA did not alter the activity of primary amine oxidase, an enzyme highly expressed in human adipose cells. Our observations indicate that, although rapid and direct, LPA impact on triglyceride storage in mature adipocytes is less pronounced than its ability to stimulate proliferation in preadipocytes.
Highlights
Among the bioactive phospholipids, lysophosphatidic acid (LPA) is considered as a remarkable growth factor in regards to its capacity to activate specific G-protein-coupled receptors named LPA1R to LPA6R [1,2] in various tissues
These observations reported in animal models of obesity and morbid obese patients are in agreement with in vitro approaches demonstrating that activation of LPA1R, the most abundant Lysophosphatidic acid (LPA)-receptor subtype expressed in adipose tissue, stimulates preadipocyte proliferation while it inhibits their differentiation into adipocytes [9,10]
The chosen dose of isoprenaline to combine with LPA was 10 nM since it was submaximal and increased basal lipolysis by a three-fold factor, allowing the detection of any further activation or inhibition elicited by a tested agent
Summary
Lysophosphatidic acid (LPA) is considered as a remarkable growth factor in regards to its capacity to activate specific G-protein-coupled receptors named LPA1R to LPA6R [1,2] in various tissues. These membrane receptors are known as endothelial differentiation G-protein-coupled receptors (EDG receptors) according to a previous nomenclature. The precursor form of this circulating activity, namely the tissue-bound ATX, is synthesized in numerous organs, including brain, lymph nodes and adipose tissue In the latter, the glycosylated enzyme ATX is released from adipocytes, catalyzes lysophosphatidic acid synthesis, which induces preadipocyte proliferation. These LPA1R-KO mice were less sensitive than WT to a high-fat diet obesogenic challenge, and diverse underlying mechanisms were proposed to explain this phenotype such as a role of LPA on food intake regulation through the modulation of leptin production and/or action
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