AAV-mediated skeletal muscle specific irisin expression does not contribute to weight loss in mice.

Autor: Bagon BB; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea., Lee J; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea., Matienzo ME; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea., Lim S; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea., Park JI; Gwangju Center, Korea Basic Science Institute (KBSI), Gwangju, 61751, South Korea., Kang S; Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea., Kim K; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea., Lee CM; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea; Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea., Moon C; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea; Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea., Kim DI; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, South Korea. Electronic address: kimdi@chonnam.ac.kr., Park MJ; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, South Korea. Electronic address: mjpark@chonnam.ac.kr.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 Nov 19; Vol. 682, pp. 111-117. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1016/j.bbrc.2023.10.004
Abstrakt: Obesity, a chronic disease, significantly increases the risk of various diseases, including diabetes, cardiovascular diseases, and cancers. Exercise is crucial for weight management not only through energy expenditure by muscle activity but also through stimulating the secretion of myokines, which affect various tissues. Irisin, derived from the proteolytic processing of fibronectin type III domain-containing protein 5 (Fndc5), is a well-studied myokine with beneficial effects on metabolism. This study explored the feasibility of adeno-associated virus (AAV)-mediated Fndc5 gene therapy to treat obesity in a mouse model using the AAV-DIO system to express Fndc5 specifically in skeletal muscle, and investigated its anti-obesity effect. Although Fndc5 was specifically expressed in the muscle, no significant impact on body weight under normal chow or high-fat diets was observed, and no change in thermogenic gene expression in inguinal white adipose tissue was detected. Notably, Fndc5 transduction did affect bone metabolism, consistent with previous reports. These findings suggest that AAV-mediated Fndc5 gene therapy may not be an efficient strategy for obesity, contrary to our expectations. Further research is needed to elucidate the complex mechanisms involved in irisin's role in obesity and related disorders.
Competing Interests: Declaration of competing interest The authors have no competing interests.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE