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Signal transducer and activator of transcription 5 negatively regulates CD36, a potential diagnostic and therapeutic target for hepatic lipid metabolism

Dear Editor, We read with great interest the recently published research article “Signal transducer and activator of transcription 5 plays a crucial role in hepatic lipid metabolism through regulation of CD36 expression” in Hepatology Research. The study showed that liver-specific signal transducer and activator of transcription 5 knockout (STAT5KO) mouse showed fat accumulation in the liver and this excess fat deposit was mostly or partially caused by increased expression of hepatic CD36 according to findings from CD36/STAT5 double-KO mice. In addition, liver-specific STAT5KO mice display severe fatty liver, with an increase in hepatic triglyceride (TG). Forced expression of hepatic CD36 was associated with significant increases in hepatic fatty acid uptake and TG deposits. Their results are of great importance, because they revealed that STAT5 and CD36 play a pivotal role in alleviating dysregulation of lipid metabolism. Recent studies have revealed that CD36/fatty acid translocase is specifically overexpressed in STATKO mice, and hepatic fatty acid uptake, mediated by CD36, plays an important role in steatosis. Deficiency of STAT5 in hepatocytes resulted in fat accumulation in the liver through CD36 upregulation, and this upregulation of CD36 is regulated by peroxisome proliferator activated receptor (PPAR)-γ and microRNA (miR)-20b. CD36 is composed of 472 amino acids and mediates fatty acid uptake, including the regulation of fatty acid uptake and indirect regulation of subsequent fatty acid oxidation. In addition, several studies suggested that CD36 expression is associated with high fat diet-induced liver steatosis and a high level of hepatic TG, as well as with unfavorable prognosis and short overall survival in chronic liver diseases. Therefore, CD36 clearly represents a relevant molecular target in hepatic steatosis. Chen et al. reported that the initiating event in GH signaling is the binding of hormone to receptor, and this activates Janus kinase 2 (JAK2). Those events activate the STAT5 signaling pathway. Thus, liver-specific deletion of STAT5-inhibited GH–JAK2–STAT5 signal transduction causes fatty liver. Zhang et al. validated that CD36 was one of the lipogenic genes induced by PPAR-γ, which is known to promote adipocyte differentiation and hepatic steatosis. In addition, it was the first time that miR-20b was identified to play a crucial role in lipid metabolism. In conclusion, STAT5 regulation of CD36 expression may be a potential therapeutic target for lipid metabolism. Although these data have conveyed much information on the association of STAT5 and CD36 with lipid metabolism, further studies are still needed to identify the mechanisms of its pathogenesis and provide more promising strategies for exploring efficient therapies.