Open AccessOmega‐3 multiple effects increasing glucocorticoid‐induced muscle atrophy: autophagic, AMPK and UPS mechanisms
Author(s) -
Fappi Alan,
Neves Juliana de C.,
Kawasaki Karine A.,
Bacelar Luana,
Sanches Leandro N.,
P. da Silva Felipe,
LarinaNeto Rubens,
Chadi Gerson,
Zanoteli Edmar
Publication year - 2019
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13966
Subject(s) - muscle atrophy , endocrinology , ampk , medicine , autophagy , atrophy , myostatin , glucocorticoid , chemistry , skeletal muscle , protein kinase a , kinase , biochemistry , apoptosis
Muscle atrophy occurs in many conditions, including use of glucocorticoids. N‐3 (omega‐3) is widely consumed due its healthy properties; however, concomitant use with glucocorticoids can increase its side effects. We evaluated the influences of N‐3 on glucocorticoid atrophy considering IGF ‐1, Myostatin, MEK / ERK , AMPK pathways besides the ubiquitin‐proteasome system ( UPS ) and autophagic/lysosomal systems. Sixty animals constituted six groups: CT , N‐3 ( EPA 100 mg/kg/day for 40 days), DEXA 1.25 ( DEXA 1.25 mg/kg/day for 10 days), DEXA 1.25 + N3 ( EPA for 40 days + DEXA 1.25 mg/kg/day for the last 10 days), DEXA 2.5 ( DEXA 2.5 mg/kg/day for 10 days), and DEXA 2.5 + N3 ( EPA for 40 days + DEXA 2.5 mg/kg/day for 10 days). Results: N‐3 associated with DEXA increases atrophy (fibers 1 and 2A), FOXO 3a, P‐ SMAD 2/3, Atrogin‐1/ MAF bx ( mRNA ) expression, and autophagic protein markers ( LC 3 II , LC 3 II / LC 3I, LAMP ‐1 and acid phosphatase). Additionally, N‐3 supplementation alone decreased P‐ FOXO 3a, PGC 1‐alpha, and type 1 muscle fiber area. Conclusion: N‐3 supplementation increases muscle atrophy caused by DEXA in an autophagic, AMPK and UPS process.