Browse > Article
http://dx.doi.org/10.5483/BMBRep.2020.53.3.093

Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA/CREB signaling in brown adipocytes  

Hossain, Monir (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
Imran, Khan Mohammad (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
Rahman, Md. Shamim (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
Yoon, Dahyeon (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
Marimuthu, Vignesh (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
Kim, Yong-Sik (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
Publication Information
BMB Reports / v.53, no.3, 2020 , pp. 142-147 More about this Journal
Abstract
Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation-related genes such as Ucp1, Pgc-1α, and Prdm16. Furthermore, structural analysis and western blot revealed that SA upregulates protein kinase A (PKA) phosphorylation with competitive inhibition by a pan-PKA inhibitor, H89. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. PKA-cat-α1 gene-silencing experiments confirmed that SA activates the thermogenic program via a mechanism involving PKA and cyclic AMP response element-binding protein (CREB) signaling. Moreover, SA treatment promoted lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation.
Keywords
Brown adipocyte; Browning; Lipolysis; PKA; Sinapic acid; UCP1;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Barneda D, Frontini A, Cinti S and Christian M (2013) Dynamic changes in lipid droplet-associated proteins in the "browning" of white adipose tissues. Biochim Biophys Acta Mol Cell Biol Lipids 1831, 924-933
2 Corona JC and Duchen MR (2015) $PPAR{\gamma}$ and $PGC-1{\alpha}$ as therapeutic targets in Parkinson's. Neurochem Res 40, 308-316   DOI
3 Natarajan P, Swargam S, Hema K, Vengamma B and Umamaheswari A (2015) E-pharmacophore based virtual screening to identify agonist for $PKA-C{\alpha}$. Biochem Anal Biochem 4, doi:10.4172/2161-1009.1000222
4 Cho IJ, Woo NR, Shin IC and Kim SG (2009) H89, an inhibitor of PKA and MSK, inhibits cyclic-AMP response element binding protein-mediated MAPK phosphatase-1 induction by lipopolysaccharide. Inflamm Res 58, 863-872   DOI
5 Lochner A and Moolman J (2006) The many faces of H89: a review. Cardiovasc Drug Rev 24, 261-274   DOI
6 Delghandi MP, Johannessen M and Moens U (2005) The cAMP signalling pathway activates CREB through PKA, p38 and MSK1 in NIH 3T3 cells. Cell Signal 17, 1343-1351   DOI
7 Watt MJ and Cheng Y (2017) Triglyceride metabolism in exercising muscle. Biochim Biophys Acta Mol Cell Biol Lipids 1862, 1250-1259   DOI
8 Park JH, Kang HJ, Kang SI et al (2013) A multifunctional protein, EWS, is essential for early brown fat lineage determination. Dev Cell 26, 393-404   DOI
9 Rosenwald M, Perdikari A, Weber E and Wolfrum C (2013) Phenotypic analysis of BAT versus WAT differentiation. Curr Protoc Mouse Biol 3, 205-216   DOI
10 Schild L, Dombrowski F, Lendeckel U, Schulz C, Gardemann A and Keilhoff G (2008) Impairment of endothelial nitric oxide synthase causes abnormal fat and glycogen deposition in liver. Biochim Biophys Acta Mol Basis Dis 1782, 180-187   DOI
11 Morris GM, Huey R, Lindstrom W et al (2009) AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 30, 2785-2791   DOI
12 Rahman N, Jeon M and Kim YS (2016) Delphinidin, a major anthocyanin, inhibits 3T3-L1 pre-adipocyte differentiation through activation of Wnt/${\beta}2*$-catenin signaling. Biofactors 42, 49-59   DOI
13 Jeon M, Rahman N and Kim YS (2016) Wnt/${\beta}$-catenin signaling plays a distinct role in methyl gallate-mediated inhibition of adipogenesis. Biochem Biophys Res Commun 479, 22-27   DOI
14 Yoon D, Imran KM and Kim YS (2018) Distinctive effects of licarin A on lipolysis mediated by PKA and on formation of brown adipocytes from C3H10T1/2 mesenchymal stem cells. Toxicol Appl Pharmacol 340, 9-20   DOI
15 Trott O and Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31, 455-461   DOI
16 Uldry M, Yang W, St-Pierre J, Lin J, Seale P and Spiegelman BM (2006) Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab 3, 333-341   DOI
17 Vijgen GH, Sparks LM, Bouvy ND et al (2013) Increased oxygen consumption in human adipose tissue from the "brown adipose tissue" region. J Clin Endocrinol Metab 98, E1230-E1234   DOI
18 Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A and Cannon B (2001) UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta Bioenerg 1504, 82-106   DOI
19 Chondronikola M, Volpi E, Borsheim E et al (2014) Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes 63, 4089-4099   DOI
20 Saito M, Yoneshiro T and Matsushita M (2016) Activation and recruitment of brown adipose tissue by cold exposure and food ingredients in humans. Best Pract Res Clin Endocrinol Metab 30, 537-547   DOI
21 Xue R, Wan Y, Zhang S, Zhang Q, Ye H and Li Y (2013) Role of bone morphogenetic protein 4 in the differentiation of brown fat-like adipocytes. Am J Physiol Endocrinol Metab 306, E363-E372
22 Kajimura S, Seale P and Spiegelman BM (2010) Transcriptional control of brown fat development. Cell Metab 11, 257-262   DOI
23 Seale P, Kajimura S, Yang W et al (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6, 38-54   DOI
24 Yuan X, Wei G, You Y et al (2016) Rutin ameliorates obesity through brown fat activation. FASEB J 31, 333-345   DOI
25 Zimmermann R, Lass A, Haemmerle G and Zechner R (2009) Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochim Biophys Acta Mol Cell Biol Lipids 1791, 494-500
26 Imran KM, Rahman N, Yoon D, Jeon M, Lee BT and Kim YS (2017) Cryptotanshinone promotes commitment to the brown adipocyte lineage and mitochondrial biogenesis in C3H10T1/2 mesenchymal stem cells via AMPK and p38-MAPK signaling. Biochim Biophys Acta Mol Cell Biol Lipids 1862, 1110-1120
27 Sell H, Deshaies Y and Richard D (2004) The brown adipocyte: update on its metabolic role. Int J Biochem Cell Biol 36, 2098-2104   DOI
28 Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E and Sul HS (2007) Regulation of lipolysis in adipocytes. Annu Rev Nutr 27, 79-101   DOI
29 Niciforovic N and Abramovic H (2014) Sinapic acid and its derivatives: natural sources and bioactivity. Compr Rev Food Sci Food Saf 13, 34-51   DOI
30 Imran KM, Yoon D, Lee TJ and Kim YS (2018) Medicarpin induces lipolysis via activation of Protein Kinase A in brown adipocytes. BMB Rep 51, 249-254   DOI
31 Song NJ, Chang SH, Li DY, Villanueva CJ and Park KW (2017) Induction of thermogenic adipocytes: molecular targets and thermogenic small molecules. Exp Mol Med 49, e353   DOI
32 Watt MJ, Holmes AG, Pinnamaneni SK et al (2006) Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Am J Physiol Endocrinol Metab 290, E500-E508   DOI
33 Anthonsen MW, Ronnstrand L, Wernstedt C, Degerman E and Holm C (1998) Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. J Biol Chem 273, 215-221   DOI