ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P583 | DOI: 10.1530/endoabs.63.P583

Metabolic effects of a novel myokine, Follistatin like protein 1 (FSTL1), in human primary adipocytes

Jung Hye Kim1, Arim Choi1, Kahui Park1, Sang Bae Lee1, YuSik Kim2, Ji Sun Nam1, Shinae Kang1, Jong Suk Park1 & Chul Woo Ahn1

1Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Republic of Korea.

Object: FSTL1, an extracellular glycoprotein, is a novel myokine that is secreted by skeletal muscle. However, its functions in metabolism remain unclear, Adipose tissue is one of the important organs for maintaining energy homeostasis. FSTL1 is known to induce inflammatory response and inhibit insulin-mediated Akt signaling pathway, we aimed to investigate whether FSTL1 play metabolic roles in human adipose tissue. We hypothesized that FSTL1 increases lipolysis through its putative receptor DIP2A (Disco interacting protein 2 homolog A).

Methods: Human primary adipocytes were treated with recombinant FSTL1 in dose and time dependent manner. To determine its lipolytic activity, pHSL ser563,565,660, perilipin, AMPK, PKA were determined by western blot and the rate of free fatty acid was assessed. Expression of DIP2A was determined by PCR and western blot. DIP2A was knocked-down to examine whether it mediates metabolic effects of FSTL1.

Results: FSTL1 did not affect catecholamine-induced lipolysis via PKA. FSTL1, however, increased lipolysis through AMPK activation and, subsequently, HSL ser565 phosphorylation in dose dependent manner. It was found that DIP2A expression did not change during differentiation of human primary adipocyte, suggesting that it is not involoved in adipocyte maturation.

Conclusion: FSTL1 increased basal lipolysis through AMPK activation. AMPK is well known sensor of the intracellular energy state and serves to regulate various signals. Its activation provides ATP by FA oxidation. Therefore, FSTL1 may play an important in the regulation of energy homeostasis. FSTL1 also has effect through DIP2A. These findings suggest that DIP2A plays important roles in FSTL1 mediated lipolysis.

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