β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats
Selvaraj Jayaraman,
Nalini Devarajan,
Ponnulakshmi Rajagopal,
Shyamaladevi Babu,
Senthil Kumar Ganesan,
Vishnu Priya Veeraraghavan,
Chella Perumal Palanisamy,
Bo Cui,
Vijayalakshmi Periyasamy,
Kirubhanand Chandrasekar
Affiliations
Selvaraj Jayaraman
Department of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai, Tamil Nadu 600077, India
Nalini Devarajan
Central Research Laboratory, Meenakshi Ammal Dental College, Meenakshi Academy of Higher Education and Research, Maduravoyal, Chennai, Tamil Nadu 600095, India
Ponnulakshmi Rajagopal
Central Research Laboratory, Meenakshi Academy of Higher Education and Research, Chennai, Tamil Nadu 600078, India
Shyamaladevi Babu
Department of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai, Tamil Nadu 600077, India
Senthil Kumar Ganesan
Structural Biology & Bioinformatics Division, TRUE Campus, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Vishnu Priya Veeraraghavan
Department of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai, Tamil Nadu 600077, India
Chella Perumal Palanisamy
State Key Laboratory of Biobased Materials and Green Papermaking, College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Science, Jinan 250353, China
Bo Cui
State Key Laboratory of Biobased Materials and Green Papermaking, College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Science, Jinan 250353, China
Vijayalakshmi Periyasamy
Department of Biotechnology and Bioinformatics, Holy Cross College, Trichy, Tamil Nadu 620002, India
Kirubhanand Chandrasekar
Department of Anatomy, All India Institute of Medical Sciences, Nagpur, Maharashtra 440025, India
β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.
