Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells

Citations Over TimeTop 11% of 2017 papers

Abstract

This study characterizes the human metabolic response to piperine, a curcumin extract, and the details of its underlying molecular mechanism. Using 1H-NMR-based metabolome analysis, we showed the metabolic effect of piperine on skeletal muscle and found that piperine increased the level of intracellular lactate, an important metabolic intermediate that controls expression of several genes involved in mitochondrial activity. Piperine also induced the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target, acetyl-CoA carboxylase (ACC), while additionally stimulating glucose uptake in an AMPK dependent manner. Piperine also stimulates the p38 mitogen-activated protein kinase (p38 MAPK), an effect that was reversed by pretreatment with compound C, an AMPK inhibitor. Inhibition of p38 MAPK resulted in no piperine-induced glucose uptake. Increased level of lactate resulted in increased expression of mitochondrial uncoupling protein 1 (UCP1), which regulates energy expenditure, thermogenesis, and fat browning. Knock-down of AMPK blocked piperine-induced UCP1 up-regulation, demonstrating the required role of AMPK in this effect. Taken together, these results suggest that piperine leads to benign metabolic effects by activating the AMPK-p38 MAPK signaling pathway and UCP1 expression by activating intracellular lactate production in skeletal muscle.

Related Papers

• → Homogenous Fluorescent Assays for Characterizing Small-Molecule Activators of AMP-Activated Protein Kinase (AMPK)(2008)2 cited
• New findings in AMP-activated protein kinase(2014)
• 돌외 추출물로부터 순수 분리된 saponin 계열의 화합물인 Damulin B에 의한 AMP-activated protein kinase (AMPK)의 활성화 기작에 대한 연구(2011)
• Coptidis Rhizoma Water Extract Stimulates 5＇-AMP-Activated Protein Kinase in Rat Skeletal Muscle(2011)
• → Faculty Opinions recommendation of AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise.(2012)