Effect of Diphlorethohydroxycarmalol Isolated From Ishige okamurae on Apoptosis in 3 t3‐L1 Preadipocytes

Abstract

Obesity is an important issue in the world of public health and preventive medicine. Inhibition of proliferation of preadipocytes plays an important role in proposed antiobesity mechanisms. In this study, we investigated the effect of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae on the apoptotic pathway. The results showed that DPHC inhibited population growth in 3 T3-L1 preadipocytes as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometric analysis of 3 T3-L1 preadipocytes showed that the number of early and late apoptotic cells increases in a dose-dependent manner after exposure to DPHC, while the number of normal cells was reduced. Our findings indicate that the induction of apoptosis in 3 T3-L1 preadipocytes by DPHC is mediated through the activation of caspase-3, Bax, and caspase-9, and then through the cleavage of poly(ADP-ribose) polymerase and the down-regulation of Bcl-2. The data also indicated that treatment with DPHC inhibits histone deacetylase activity in 3 T3-L1 preadipocytes. These results show that DPHC efficiently induces apoptosis in 3 T3-L1 preadipocytes.

Di and tripeptides from marine sources can target adipogenic process and contribute to decrease adipocyte number and functions

“…This was already demonstrated by a number of natural products such as polyphenol compounds which were shown to inhibit preadipocytes proliferation and induce apoptosis. For example, quercetin and diphlorethohydroxycarmalol (DPHC) induced apoptosis in 3T3-L1 pre-adipocyte by decreasing mitochondria membrane potential, down-regulating poly (ADP-ribose) polymerase (PARP), Bcl-2 and activating caspase 3, Bax and Bak (Park et al, 2013;Rayalam et al, 2008). Kim et al (2006) suggested that adipocytes deletion by apoptosis could be a contributor to body fat loss.…”

“…These data demonstrate the urgency to establish effective strategies for prevention and treatment of obesity. Among ways to reduce obesity, the decrease of energy/food intake and the increase of energy expenditure (Park, Jeon, Kim, & Han, 2013) are of importance but targeting adipocyte physiology and cell cycle could also be a solution. Indeed, recent studies have examined how far inhibition of preadipocyte proliferation, differentiation, lipogenesis or promotion of lipolysis and fat oxidation (Wang & Jones, 2004) can reduce obesity.…”

“…Obesity is characterized at the cellular level by an increase in the number and size of adipocytes originating from fibroblastic preadipocytes in adipose tissues (Furuyashiki et al, 2004). Preadipocytes, which can then be differentiated into mature adipocytes and modulate body fat mass, play a key role in obesity (Park et al, 2013). At a molecular level, differentiation is a well-organized program characterized by the loss of pre-adipocyte markers and sequential changes in the expression of general and adipocytespecific genes that determine the specific adipocyte phenotype (Catalioto, Maggi, & Giuliani, 2009).…”

6,6′‐Bieckol inhibits adipocyte differentiation through downregulation of adipogenesis and lipogenesis in 3T3‐L1 cells

“…26 Additionally, Park et al reported an effect of diphlorethohydroxycarmalol isolated from Ishige okamurae on apoptosis in 3 T3-L1 preadipocytes, and then confirmed through a transcription factor such as fatty acid synthase. 27 ACC is another key enzyme in lipogenesis that is regulated by the transcription factor SREBP-1c. Given that the inhibition of ACC is a crucial step in the reduction of lipid accumulation, this enzyme and FAS should be targeted in anti-obesity research.…”

Marine Algae as a Potential Source for Anti-Obesity Agents

“…Phloroglucinol and eckol suppressed adipogenesis by down-regulating C/EBPα and PPARγ while dieckol acted by activating AMP activated protein kinase (AMPK) and inhibiting PPARγ [89]. Another phlorotannin, diphlorethohydroxycarmalol (DPHC), from Ishigeo kamurae, caused apoptosis of preadipocytes [90]. However, there have been no reports on studies on mature adipocytes.…”