Open AccessPiperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells
Author(s) -
Nami Kim,
Miso Nam,
Mi Sun Kang,
Jung Ok Lee,
Yong Woo Lee,
Gwi Seo Hwang,
Hyeon Soo Kim
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep41066
Subject(s) - piperine , ampk , protein kinase a , amp activated protein kinase , skeletal muscle , chemistry , glucose uptake , p38 mitogen activated protein kinases , intracellular , biochemistry , phosphorylation , microbiology and biotechnology , biology , endocrinology , insulin , organic chemistry
This study characterizes the human metabolic response to piperine, a curcumin extract, and the details of its underlying molecular mechanism. Using 1 H-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.