Lipid Inhibitory Effect of (−)-loliolide Isolated from Sargassum horneri in 3T3-L1 Adipocytes: Inhibitory Mechanism of Adipose-Specific Proteins

Abstract

Sargassum horneri (S. horneri) is a well-known brown seaweed widely distributed worldwide. Several biological activities of S. horneri have been reported. However, its effects on lipid metabolism and the underlying mechanisms remain elusive. In the present study, we examined the inhibitory effect of the active compound “(−)-loliolide ((6S,7aR)-6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydro-1-benzofuran-2(4H)-one (HTT))” from S. horneri extract on lipid accumulation in differentiated adipocytes. MTT assays demonstrated that (−)-loliolide is not toxic to 3T3-L1 adipocytes in a range of concentrations. (−)-loliolide significantly reduced intracellular lipid accumulation in the differentiated phase of 3T3-L1 adipocytes as shown by Oil Red O staining. Western blot analysis revealed that (−)-loliolide increased the expression of lipolytic protein phospho-hormone-sensitive lipase (p-HSL) and thermogenic protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1). Additionally, (−)-loliolide decreased expression of adipogenic and lipogenic proteins, including sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid-binding protein 4 (FABP4) in 3T3-L1 adipocytes. These results indicate that (−)-loliolide from S. horneri could suppress lipid accumulation via regulation of antiadipogenic and prolipolytic mechanisms in 3T3-L1 cells. Considering the multifunctional effect of (−)-loliolide, it can be useful as a lipid-lowering agent in the management of patients who suffer from obesity.

The Marine Alga Sargassum horneri Is a Functional Food with High Bioactivity

“…We found that the S. horneri water extract component enhanced the insulin-stimulated differentiation of bone marrow stem cells into osteoblasts and suppressed the formation of adipocytes [35]. S. horneri extract also has inhibitory effects on lipid metabolism in 3T3-L1 adipocytes in vitro [36]. Thus, the S. horneri component may have the effect of suppressing the differentiation of bone marrow cells into adipocytes.…”

Centranthus ruber (L.) DC. and Tropaeolum majus L.: Phytochemical Profile, In Vitro Anti-Denaturation Effects and Lipase Inhibitory Activity of Two Ornamental Plants Traditionally Used as Herbal Remedies

“…Cinnamic acid, detected in both samples, interestingly showed in vivo anti-obesity activity in high fat diet-fed rats [48]. The monoterpene lactone loliolide was demonstrated to significantly reduce the intracellular lipid accumulation in 3T3-L1 adipocytes [49].…”

Anti-Adipogenic Activity of Secondary Metabolites Isolated from Smilax sieboldii Miq. on 3T3-L1 Adipocytes

“…Thus, this cell line is a suitable screening model for obesity-related adipose tissue biology. Some natural products and plant extracts, such as Abelmoschus manihot [12], Albizia julibrissin [13], Amomum tsao-ko [14], indole derivatives [15], (−)loliolide [16], kaempferol [17], Salix pseudolasiogyne [18], and shrimp oil [19], are known to prevent the lipid accumulation or the differentiation of adipocytes in 3T3-L1 cells.…”

“…In our present research, we conducted investigations to identify potential bioactive phytochemicals in the ethyl acetate (EtOAc) and methylene chloride (CH 2 Cl 2 ) fraction of the S. sieboldii EtOH extract. We included chromatographic purification and structural identification of one undescribed α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18), which were isolated along with additional known constituents (1-15 and 19). The structure of the novel constituents was characterized using various spectral experiments (1D/2D NMR and HR-MS) and specific optical rotation analyses.…”