Impact of myokines on AMPK activity in obesity-induced chronic kidney disease

The growing increase of obesity intensifies incidence of chronic kidney disease (CKD) across the world. Our group demonstrated that the AMP-activated protein kinase (AMPK) dysregulation is a key driver of the obesity-induced CKD progression. Moreover, we showed that endurance exercise training (EET) mediates improvements in renal function in obese mice though the restoration of AMPK activity. Thus, we hypothesize that myokines produced during exercise are involved in the beneficial effects of EET on renal impairments. Among myokines, irisin has been recently highlighted to have beneficial effect on kidney. Therefore, here, the impact of irisin on the AMPK activity and renal metabolic adaptation to lipotoxicity was investigated in primary proximal tubular epithelial cells (PTEC) to identify its benefit in CKD treatment.

To do so, PTEC were isolated from mouse kidneys (mPTEC). The functional characteristics of mPTEC was validated using the BSA-uptake assay, highlighting the absorptive ability of these cells. To mimic the obesity setting, cultured cells were treated with palmitic acid (PA) or its vehicle in presence or not of irisin, during 24 h.
We first confirmed that lipid overload in mPTEC alters their function of protein reabsorption and induces significant lipid droplet accumulation. These changes were associated to an increase in PPAR-gamma transcription factor and its targeted gene, CD36. Interestingly, irisin seems to prevent the lipid accumulation along to preventing PPAR-gamma and CD36 gene expression. In addition, mRNA expression of key players in lipogenesis and beta oxidation were investigated. While PA treatment induces an increase in β-oxidation gene expression and a reduction of lipogenesis gene expression, irisin did not prevent these changes.
Our data showed beneficial impact of irisin on renal lipotoxicity. This might be linked to a better mitochondrial fitness. Therefore, it will be interesting to deeper investigate mitochondrial biogenesis, dynamic and function.