Chloroquine modulates the sulforaphane anti-obesity mechanisms in a high-fat diet model: Role of JAK-2/ STAT-3/ SOCS-3 pathway

Abstract

The phytochemical sulforaphane (SFN) has been studied for its potential anti-obesity effect, but neither its molecular targets nor its interaction with the antimalarial drug chloroquine (CQ) has been fully delineated. Therefore, high-fat diet (HFD) obese rats were randomly allocated into one of five groups and were left untreated or gavaged orally with SFN (0.5 or 1 mg/kg), CQ (5 mg/kg), or their combination (0.5/5 mg/kg) for six successive weeks to assess their potential interaction and the enrolled mechanisms. SFN effectively reduced the HFD-induced weight gain, blood glucose, and serum leptin levels, and improved lipid profile. On the molecular level, SFN inhibited the lipogenesis-related enzymes, namely sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in both liver and visceral white adipose tissue (vWAT) of HFD obese rats. SFN also turned off the inflammatory pathway conserved Janus kinase/signaling transducers and activators of transcription/suppressor of cytokine signaling (JAK-2/STAT-3/SOCS-3) in these tissues, as well as the inflammatory markers nuclear factor-kappa (NF-κ) B and interleukin (IL)-22 in serum. In contrast, SFN downregulated the gene expression of microRNA (miR-200a), while significantly increasing the autophagic parameters; viz., beclin-1, autophagy-related protein (ATG)-7, and microtubule-associated protein 2 light chain 3 (LC3-II) in both liver and vWAT. On most of the parameters mentioned above, treatment with CQ solely produced a satisfactory effect and intensified the low dose of SFN in the combination regimen. These findings demonstrated the beneficial effects of using CQ as an add-on anti-obesity medicine to SFN.