?MSH inhibits adipose inflammation via reducing FoxOs transcription and blocking Akt/JNK pathway in mice.

ABSTRACT: Alpha melanocyte stimulating hormone (?MSH) abates inflammation in multiple tissues, while Forkhead box proteins O (FoxOs) stimulate inflammatory cascade. However, the relationship between ?MSH and FoxOs in adipose inflammation remains unclear. In this study, we used LPS-induced inflammation model, attempted to interpret the function of ?MSH in inflammation and the interactions with FoxOs. Results indicated that upon inflammatory situation, the secretion of ?MSH and the expression of its receptor MC5R were greatly decreased, but FoxOs expressions were elevated. After the treatment with ?MSH, LPS-induced adipose inflammation together with FoxOs expressions was significantly reduced. Conversely, when Foxo1, Foxo3a or Foxo4 overexpressed in ?MSH treated inflammatory mouse model, all the anti-inflammatory impacts of ?MSH were found disappeared. We further studied the mechanisms by which ?MSH exerts its anti-inflammatory impacts and how FoxOs reverse ?MSH's function. Foxo4 was found as a negative regulator for MC5R transcription in ?MSH inhibited inflammation. Moreover, a negative role was found of ?MSH in regulating both Akt and JNK signal pathways by observing the enhanced the anti-inflammatory impacts of pathway-specific inhibitors with ?MSH treatment. Our findings demonstrate ?MSH plays a key role in the prevention of adipose inflammation and inflammatory diseases by down-regulating Akt/JNK signal pathway and negatively interacting with FoxOs, which brings up ?MSH as a novel candidate factor in the adipose anti-inflammation process in obesity.

SUBMITTER: Liu G 

PROVIDER: S-EPMC5564594 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature