Love Sharma, Rachel M Knott and Tasduq Abdullah
Robert Gordon University, UK
CSIR-Indian Institute of Integrative Medicine, India
Academy of Scientific and Innovative Research, India
Posters & Accepted Abstracts: J Diabetes Metab
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with type 2 diabetes mellitus (T2DM). Trigoneline (TE), a plant alkaloid known for its anti-oxidant and normoglycameic properties, was analyzed for its anti-steatotic effects. AML-12 hepatocytes and sodium palmitate (SP) were employed as an in-vitro model. AML-12 cells were pretreated with 25 μM and 50 μM doses of TE 4 hours before, exposure to 0.25 mM of SP for 24 hours. Key events related to lipo-toxicity and lipid droplet accumulation (via Nile red staining) were analyzed. In-vivo, C57BL/6J male mice (n=6), were divided into four groups as follows: 1) Standard chow (SC); 2) high fructose and high cholesterol diet (HF-HC), 3) HF+HC & TE (50 mg/kg, thrice a week) 4) SC & TE (50 mg/kg, thrice a week).The mice were provided respective diets and TE treatment for 16 weeks. TE treatment in AML-12 cells, prevented SP induced cell death, [34% (SP 0.25mM + TE 0 μM), 21% (SP 0.25mM+TE 25 μM/50 μM)], further evidenced by changes in protein levels (Bcl-2, Bax, cl-PARP and MMP-1). TE reduced SP promoted lipid droplet accumulation and reduced the expression of perillipin analyzed via immunocytochemistry. TE prevented upregulation of PPAR-γ, SREBP1c, m-TOR, p-mTOR, p-AKT, induced by SP. In-vivo, Group 2 mice were significantly overweight (45±2.4 g), as compared to Group 3 mice (33±2.1 g, p<0.01). The level of glucose (355±47.3 mg/dl), insulin (5.3±0.3 ng/ ml), triglycerides (146±19.5 mg/dl), and cholesterol (351±51 mg/dl) were significantly high in Group 2 mice as compared to all other groups. Group 1 and Group 4 were not statistically different in any of the measured values. Hence, our results indicate that TE potentially prevents lipid droplet accumulation and lipotoxicity in liver cells, and it may be suitable as a therapeutic agent to combat NAFLD.
Love Sharma is a Senior Research Fellow (PhD scholar) at CSIR-IIIM, Jammu. Currently, he is on short term research project (Under Newton-Bhabha Scheme) at School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen. His area of research includes the metabolic syndrome, therapeutic interventions for non-alcoholic fatty liver disease including in-vitro and in-vivo model development.
