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Abstract
Suppressor of cytokine signaling 2 (SOCS2) plays an important role in fat deposition, skeletal muscle, central nervous system development, and mitochondria biogenesis. Nevertheless, the regulatory mechanisms of SOCS2 on mitochondrial fatty acid oxidation (FAO) remain unclear. Leptin could inhibit food intake and increase thermogenesis through leptin receptor (LepR), which was present in the hypothalamus and certain peripheral organs, including adipose tissue. With strong interest, we focused on the connection between leptin and SOCS2 and their effect on FAO in adipocytes. In our study, we found that the mRNA level of SOCS2 and the protein levels of PGC-1α, CPT-1b, FAT, and p-ACC were elevated by leptin in the inguinal adipose tissue of mice. On the contrary, the protein levels of FABP4, FATP1, and FAS were declined. The genes related to fatty acid oxidation such as PGC-1α, NRF-1, TFAM, CPT-1b, AOX1, COX2, and UCP2 were attenuated by SOCS2, but elevated by leptin. Moreover, fatty acid oxidation enzyme MCAD, LCAD, and Cyt C levels were reduced in response to SOCS2. These reductions correspond well with the reduced release of free fatty acid and the reduction of mitochondrial complexes I and III by SOCS2. Furthermore, JAK2/AMPK pathway-specific inhibitors could block the mitochondrial FAO; hence, this pathway was implied to have a potential impact on FAO. Together, these studies suggested that SOCS2 had a negative effect on mitochondrial fatty acid oxidation, and the LepR/JAK2/AMPK pathway played a crucial role in this process.
Highlights
The suppressor of cytokine signaling (SOCS), as an inhibitor of cytokine signaling pathways, downregulates the signal pathway Janus kinase/signal transducers and activators of transcription (JAK/STAT) in several interconnected mechanisms [1]
Our previous research showed that Suppressor of cytokine signaling 2 (SOCS2) was an important negative regulator of GH signaling in porcine adipocytes and inhibited mitochondria biogenesis in C2C12 cells [2, 6]
Fatty acidbinding protein 4 (FABP4) protein level was reduced after leptin treatment (P < 0:05, Figure 1(e))
Summary
The suppressor of cytokine signaling (SOCS), as an inhibitor of cytokine signaling pathways, downregulates the signal pathway Janus kinase/signal transducers and activators of transcription (JAK/STAT) in several interconnected mechanisms [1]. SOCS3 is demonstrated as a major negative regulator of both leptin and insulin signaling, and SOCS3 overexpression in muscle suppresses leptin-regulated genes involved in fatty acid oxidation and mitochondrial functions [15, 16]. Leptin activates the AMPK pathway and stimulates fatty acid oxidation by blocking the effect of acetyl-CoA carboxylase (ACC) in the skeletal muscle [21]. We contrasted the different roles of SOCS2 and leptin in fatty acid oxidation and further investigated the mechanism of SOCS2 on mitochondrial fatty acid oxidation in mouse adipocytes. These data were devoted to contributing to fundamental research of energy homeostasis and the prevention and treatment of related metabolic diseases
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