Investigating the crosstalk between and in 3T3-L1 adipocyte differentiation.

INTRODUCTION

The plasma membrane-bound protein, multi-drug resistance-associated protein 4 (), has gained attention for its pivotal role in facilitating the efflux of a wide range of endogenous and xenobiotic molecules. Its significance in adipogenesis and fatty acid metabolism has been brought to light by recent studies. Notably, research on knockout ( ) mice has established a link between the absence of and the development of obesity and diabetes. Nevertheless, the specific contribution of within adipose tissue remains largely unexplored.

METHODS

To address this gap, we conducted a study to elucidate the role of the transporter in mature adipocytes, using siRNA constructs to silence its gene function.

RESULTS

The successful knockdown of significantly altered lipid status and adipogenic gene expression in mature 3T3-L1 adipocytes. Intriguingly, this knockdown also altered the gene expression patterns of other transporter family members in 3T3-L1 cells. The downregulation of expression was particularly noteworthy, suggesting potential crosstalk between transporters in mature adipocytes. Additionally, knocking down resulted in significantly higher adipogenic and lipogenic gene expression levels. Oil Red O staining confirmed increased lipid accumulation following the knockdown of and . Surprisingly, the simultaneous knockdown of both transporters did not show a cumulative effect on adipogenesis, rather it led to higher levels of intracellular cAMP and extracellular prostaglandin metabolite, both of which are essential signaling molecules in adipogenesis.

CONCLUSION

These results highlight the complex interplay between and transporters in adipocyte function and suggest their individual contributions toward obesity and related disorders.