Abstract
BackgroundThe postprandial regulation of angiopoietin-like proteins (Angptls) and their expression in adipocytes is poorly characterized.ObjectiveCirculating Angptl3 and 4 were analyzed in healthy individuals undergoing either an oral lipid tolerance test (OLTT; n = 98) or an oral glucose tolerance test (OGTT; n = 99). Venous blood was drawn after 0, 2, 4, and 6 h during OLTT and after 0, 1, and 2 h during OGTT. Anthropometric and laboratory parameters were assessed and concentrations of Angptls were quantified by enzyme-linked immunosorbent assay. Angptl gene expression in 3T3-L1 adipocytes and in murine adipose tissues and cellular fractions was analyzed by quantitative real-time PCR.ResultsAngptl3 concentrations significantly decreased while Angptl4 levels continuously increased during OLTT. Both proteins remained unaffected during OGTT. Angptl3 and Angptl4 were expressed in murine subcutaneous and visceral AT with higher mRNA levels in mature adipocytes when compared to the stroma-vascular cell fraction. Both proteins were strongly induced during 3T3-L1 adipocyte differentiation and they were unresponsive to glucose in mature fat cells. Adipocyte Angptl3 (but not Angptl4) mRNA expression was inhibited by the polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid, whereas nine types of dietary fatty acids remained without any effect.ConclusionsThere is evidence of short-time regulation of Angptl3/4 levels upon metabolic stress. Angptl4 expression is high and Angptl3 expression is low in AT and restricted mainly to mature adipocytes without any differences concerning fat compartments. Whereas dietary fatty acids and glucose are without any effect, omega-3/-6-polyunsaturated fatty acids inhibited Anptl3 expression in adipocytes.
Highlights
Besides its “classical” function in energy storage/release and as an isolating and structural tissue, investigations during the last three decades have led to an understanding of the adipose tissue as an active endocrine gland and an immunological organ substantially involved in inter-organ and inter-cellular communication [1,2,3,4,5]
It has an important role in the regulation of adipose tissue lipid metabolism and plasma free fatty acid levels (FFA), thereby acting as an hepatokine inducing lipolysis in adipocytes [17, 18]
A clinical trial investigating the effect of ethinyl estradiol-cyproterone acetate in adolescent girls with androgen excess reported that the expression of Angptl4 in subcutaneous adipose tissue significantly increased upon hormonal treatment [45]
Summary
Besides its “classical” function in energy storage/release and as an isolating and structural tissue, investigations during the last three decades have led to an understanding of the adipose tissue as an active endocrine gland and an immunological organ substantially involved in inter-organ and inter-cellular communication [1,2,3,4,5] These pleiotropic effects are mainly mediated by so-called adipokines, including a plethora of diverse adipocyte-secreted proteins and peptides exerting endocrine, paracrine, and autocrine effects [6,7,8]. Results Angptl concentrations significantly decreased while Angptl levels continuously increased during OLTT Angptl and Angptl were expressed in murine subcutaneous and visceral AT with higher mRNA levels in mature adipocytes when compared to the stroma-vascular cell fraction Both proteins were strongly induced during 3T3-L1 adipocyte differentiation and they were unresponsive to glucose in mature fat cells. Whereas dietary fatty acids and glucose are without any effect, omega-3/-6-polyunsaturated fatty acids inhibited Anptl expression in adipocytes
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