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Effects of Piperine on Insulin Resistance and Lipid Accumulation in Palmitate- treated HepG2 Cells

Journal of Life Science 2019년 29권 9호 p.964 ~ 971
 ( Jung Hee-Jin ) - Pusan National University Longevity Life Science and Technology Institute

 ( Bang Eun-Jin ) - Pusan National University College of Pharmacy Department of Pharmacy
 ( Jeong Seong-Hoon ) - Pusan National University College of Pharmacy Department of Pharmacy
 ( Kim Byeong-Moo ) - Pusan National University College of Pharmacy Department of Pharmacy
 ( Chung Hae-Young ) - Pusan National University College of Pharmacy Department of Pharmacy


Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.


Insulin resistance; lipid accumulation; palmitate; piperine
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