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Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes

Authors
Kim, YejinKim, Hyun KyungKang, SuminKim, HayoonGo, Gwang-woong
Issue Date
Sep-2023
Publisher
KOREAN SOCIETY FOOD SCIENCE & TECHNOLOGY-KOSFOST
Keywords
Rottlerin; Adipogenesis; De novo lipogenesis; The nutrient-sensing mTOR pathway
Citation
FOOD SCIENCE AND BIOTECHNOLOGY, v.32, no.10, pp.1445 - 1452
Indexed
SCIE
SCOPUS
KCI
Journal Title
FOOD SCIENCE AND BIOTECHNOLOGY
Volume
32
Number
10
Start Page
1445
End Page
1452
URI
https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/188410
DOI
10.1007/s10068-023-01339-5
ISSN
1226-7708
Abstract
Rottlerin is isolated from Mallotus japonicus, a plant rich in polyphenols. Rottlerin is a selective PKC & delta;-inhibitor and is also known as an uncoupler of oxidative phosphorylation and anti-neoplastic agent. However, its anti-obesity effect is yet to be established. Therefore, this study tested whether rottlerin inhibits adipogenesis and de novo lipogenesis via the LRP6/mTOR/SREBP1C pathway in 3T3-L1 adipocytes. Rottlerin dramatically decreased lipid accumulation assessed by Oil Red O as evidence to support the cellular phenotype (p < 0.001). Pivotal messenger RNA and protein expressions associated with de novo lipogenesis (SREBP1C, ACC1, FAS, and SCD1) and adipogenesis (PPAR & gamma; and C/EBP & alpha;) were subsequentially verified by rottlerin in a dose-dependent manner (p < 0.05). Further investigation revealed that rottlerin reduced the AKT/mTOR pathway via diminished total protein of LRP6 (p < 0.05). Collectively, these findings establish a causal link between rottlerin, LRP6, and the altered nutrient-sensing mTOR pathway, in which rottlerin regulates de novo lipogenesis and adipogenesis in white adipocytes.
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COLLEGE OF HUMAN ECOLOGY (DEPARTMENT OF FOOD & NUTRITION)
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