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

Title
Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells
Authors
Kim, NamiNam, MisoKang, Mi SunLee, Jung OkLee, Yong WooHwang, Geum-SookKim, Hyeon Soo
Ewha Authors
황금숙
SCOPUS Author ID
황금숙scopusscopus
Issue Date
2017
Journal Title
SCIENTIFIC REPORTS
ISSN
2045-2322JCR Link
Citation
vol. 7
Publisher
NATURE PUBLISHING GROUP
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
This study characterizes the human metabolic response to piperine, a curcumin extract, and the details of its underlying molecular mechanism. Using H-1-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.
DOI
10.1038/srep41066
Appears in Collections:
자연과학대학 > 화학·나노과학전공 > Journal papers
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