Tetranectin Promotes Adipogenesis and Lipogenesis and is Negatively Regulated by Polyunsaturated Fatty Acids in Human Adipocytes

Abstract

Adipose tissues secrets factors, or adipokines, regulate body energy homeostasis. To search for novel adipokines, we employed 2‐D protein gel electropherosis and LC‐MS/MS to analyze human primary adipocyte culture medium, in which tetranectin (TN). We found that the mRNA expression of TN is positively correlated with the differentiation and lipid accumulation of human preadipocytes, as well as the body mass index. Overexpression and knockdown of TN in human primary adipocytes by lentivirus prove that TN increases the expression of adipogenic and lipogenic genes, such as peroxisome proliferator‐activated receptor gamma, lipoprotein lipase and fatty acid synthesis, but decreases those related to lipolysis, including hormone sensitive lipase, interleukin 6 and serum amyloid A along with altered profiles of proteins responsible primarily for lipid metabolism, as analyzed by quantitative proteomic analysis and quantitative real‐time PCR. In addition, treatments of polyunsaturated fatty acids (PUFA) suppressed TN expression. Taken together, our data suggest that not only TN potentially serves as a novel adipokine contributing to the regulation of energy homeostasis and lipid metabolism, but also components of the TN‐associated signaling pathways the therapeutic targets for treating obesity and associated metabolic diseases.

Docosahexaenoic Acid Suppresses Expression of Adipogenic Tetranectin through Sterol Regulatory Element-Binding Protein and Forkhead Box O Protein in Pigs

“…Our preliminary results [20] and other studies showed that, by 2-D LC-MS/MS or quantitative proteomics, conditioned media from adipocyte differentiation processes or mature adipocytes contain secreted TN in humans [40], mice [41][42][43], and rats [44]. This suggests that TN is an adipokine related to adipocyte adipogenesis, although one study showed that TN expression is downregulated after adipocyte differentiation [23].…”

“…This study revealed that TN expression in porcine adipose tissues and primary adipocytes is congruent with our previous preliminary results, indicating that TN is an adipokine that is secreted by human differentiated mature adipocytes, increased during adipogenesis of human adipocytes and positively correlated with body mass index of human subjects. TN is also increased in obese mice when fed a high-fat diet for 16 weeks, and overexpression of TN in human adipocytes results in lipid accumulation and elevated lipogenic gene expression [20]. Therefore, TN may play an important role in adipogenesis in humans, mice and pigs.…”

“…From our preliminary results, TN is an adipokine secreted by human adipocytes; it is increased during adipogenesis of human adipocytes, positively correlated with the body mass index of clinical subjects and upregulated by high-fat feeding in mice [20]. Therefore, the aim of this study was to investigate the nutritional modulation of TN expression by DHA in animal models and human cell lines.…”