Irisin exerts dual effects on browning and adipogenesis of human white adipocytes

Yuan Zhang, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida; Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan, China;
Chao Xie, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;
Hai Wang, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;
Robin M. Foss, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;
Morgan Clare, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;
Eva Vertes George, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;
Shiwu Li, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;
Adam Katz, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida;
Henrique Cheng, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana;
Yousong Ding, Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery, and Development, College of Pharmacy, University of Florida, Gainesville, Florida; and.
Dongqi Tang, Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan, China;
Westley H. Reeves, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida.
Li-Jun Yang, Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida; yanglj@pathology.ufl.edu.

Document Type

Article

Publication Date

8-1-2016

Abstract

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes "browning" of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.

Publication Source (Journal or Book title)

American journal of physiology. Endocrinology and metabolism

First Page

E530

Last Page

41

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