Purpose: Skeletal muscle-adipose tissue crosstalk is important for maintaining metabolic homeostasis. Myokine plays an indispensable role in the skeletal muscle-adipose tissue crosstalk. This study was conducted to elucidate the association between Omega-3 polyunsaturated fatty acids (n-3 PUFAs) and myokine and figure out the role of n-3 PUFAs in the skeletal muscle-adipose tissue crosstalk.
Methods: The mRNA expression of myokines, including IL-6, Irisin, IL-15, myostatin, FGF21, adiponectin, leptin and TNF-α, in myotube cells incubated with ALA, DHA, EPA, and DHA/EPA mixture for 24 h were evaluated. 3T3-L1 adipocytes were treated with the culture supernatant of myotube cells incubated with the DHA/EPA mixture, and the mRNA levels of genes associated with lipid metabolism and browning were evaluated. Moreover, the level of p-AMPK and PGC-1α were evaluated to determine whether AMPK signaling was involved in the process of n-3 PUFAs regulating myokines expression.
Results: Different forms of n-3 PUFAs increased the expression of multiple myokines in C2C12 myotubes. The expression of p-AMPK and PGC-1α in C2C12 myotubes were up-regulated by DHA/EPA mixture and Metformin. Except Irisin, the expression of other myokines was further up-regulated after inhibiting AMPK. The culture supernatant of myotube cells incubated with the DHA/EPA mixture regulated the lipid metabolism-related genes and stimulated browning in adipocytes.
Conclusions: n-3 PUFAs play roles in the skeletal muscle-adipose tissue crosstalk by regulating the expression and release of myokines associated with lipid metabolism and browning. Part of the mechanism of this process should be attributed to DHA/EPA activating AMPK signaling in C2C12 myotube.