Seong-Il Kang

Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes.

Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPARγ, C/EBPα, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

p-Coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase in L6 skeletal muscle cells.

p-Coumaric acid (3-[4-hydroxyphenyl]-2-propenoic acid) is a ubiquitous plant metabolite with antioxidant, anti-inflammatory, and anticancer properties. In this study, we examined whether p-coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase (AMPK) in L6 skeletal muscle cells. p-Coumaric acid increased the phosphorylation of AMPK in a dose-dependent manner in differentiated L6 skeletal muscle cells. It also increased the phosphorylation of acetyl-CoA carboxylase (ACC) and the expression of CPT-1 mRNA and PPARα, suggesting that it promotes the β-oxidation of fatty acids. Also, it suppressed oleic acid-induced triglyceride accumulation, and enhanced 2-NBDG uptake in differentiated L6 muscle cells. Pretreatment with compound C inhibited AMPK activation, reduced ACC phosphorylation and 2-NBDG uptake, and increased triglyceride accumulation. However, p-coumaric acid counterbalanced the inhibitory effects of compound C. Taken together, these results suggest that p-coumaric acid modulates glucose and lipid metabolism via AMPK activation in L6 skeletal muscle cells and that it has potentially beneficial effects in improving or treating metabolic disorders.

Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinase.

In this study, we investigated the antiobesity properties of Petalonia binghamiae extract (PBE) in mice in which obesity was induced with a high-fat diet (HFD). PBE administration (150 mg/kg/day) for 70 days decreased body weight gain, adipose tissue weight, and the serum triglyceride level in mice fed a HFD. PBE reduced serum levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as the accumulation of lipid droplets in the liver. PBE restored the HFD-induced decrease in phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. PBE increased the phosphorylation of AMPK and ACC and decreased the expression of SREBP1c in mature 3T3-L1 adipocytes. In addition, we further explored the active compound responsible for AMPK activation by PBE in 3T3-L1 adipocytes. Fucoxanthin isolated from PBE increased the phosphorylation of AMPK and ACC with increasing LKB1 phosphorylation in mature 3T3-L1 adipocytes. Taken together, these data suggest that PBE (or fucoxanthin) exert improving effects on HFD-induced obesity by promoting β-oxidation and reducing lipogenesis.

A water-soluble extract of Petalonia binghamiae inhibits the expression of adipogenic regulators in 3T3-L1 preadipocytes and reduces adiposity and weight gain in rats fed a high-fat diet

We previously showed that an ethanolic extract of the edible brown algae Petalonia binghamiae promotes the differentiation of 3T3-L1 preadipocytes and decreases hyperglycemia in streptozotocin-induced diabetic mice. Here, we report that a water-soluble extract of P. binghamiae thalli, prepared by enzymatic digestion, inhibits preadipocyte differentiation and adipogenesis in a dose-dependent manner. In differentiating 3T3-L1 preadipocytes, the extract (designated PBEE) decreased the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding proteins α and β, and fatty acid-binding protein aP2. It also inhibited the mitotic clonal expansion process of adipocyte differentiation, and it inhibited insulin-stimulated uptake of glucose into mature 3T3-L1 adipocytes by reducing phosphorylation of insulin receptor substrate-1. In rats with high-fat diet (HFD)-induced obesity, PBEE exhibited potent anti-obesity effects. In this animal model, increases in body weight and fat storage were suppressed by the addition of PBEE to the drinking water at 500 mg/L for 30 days. PBEE supplementation reduced serum levels of glutamic pyruvic and glutamic oxaloacetic transaminases and increased the serum level of high-density lipoprotein cholesterol. Moreover, it significantly decreased the accumulation of lipid droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Taken together, these data demonstrate that PBEE inhibits preadipocyte differentiation and adipogenesis in cultured cells and in rodent models of obesity.

Sasa quelpaertensis Nakai extract and its constituent p-coumaric acid inhibit adipogenesis in 3T3-L1 cells through activation of the AMPK pathway.

In this study, we investigated the effects of Sasa quelpaertensis Nakai extract (SQE) and its main constituent, p-coumaric acid, on adipogenesis in 3T3-L1 cells. SQE markedly inhibited adipogenesis by downregulating the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP-1c), and aP2. It also decreased the expression of fatty acid synthase (FAS) and adiponectin mRNAs in differentiating adipocytes. SQE increased AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation during the early phase of MDI-induced differentiation, suggesting that SQE exerted its anti-adipogenic effect via AMPK activation at an early stage of the differentiation process. p-Coumaric acid suppressed adipogenesis by attenuating the expression of C/EBPα, PPARγ, and SREBP-1c during the late phase of MDI-induced differentiation. In addition, p-coumaric acid increased the phosphorylation of AMPK and ACC, and the expression of carnitine palmitoyl transferase-1 (CPT-1) mRNA, in fully differentiated adipocytes, indicating that it promotes fatty acid β-oxidation via AMPK signaling. Taken together, our data suggest that SQE and p-coumaric acid might have the anti-obesitic effects via AMPK pathway in 3T3-L1 cells.

Anti-Obesity Properties of a Sasa quelpaertensis Extract in High-Fat Diet-Induced Obese Mice

This study explores the anti-obesity properties of a Sasa quelpaertensis leaf extract (SQE) in high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. SQE administration with HFD for 70 d significantly decreased the body weight gain, adipose tissue weight, and serum total cholesterol and triglyceride levels in comparison with the HFD group. SQE administration also reduced the serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate dehydrogenase, and the accumulation of lipid droplets in the liver, suggesting a protective effect against HFD-induced hepatic steatosis. SQE administration restored the HFD-induced decreases with phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. SQE also induced AMPK phosphorylation in mature 3T3-L1 adipocytes. These results suggest that SQE exerted an anti-obesity effect on HFD-induced obese mice by activating AMPK in adipose tissue and reducing lipid droplet accumulation in the liver.

Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor gamma (PPARgamma) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARgamma luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.

Sasa quelpaertensis and p-Coumaric Acid Attenuate Oleic Acid-Induced Lipid Accumulation in HepG2 Cells

In this study, we examined the effects of Jeju dwarf bamboo (Sasa quelpaertensis Nakai) extract (JBE) and p-coumaric acid (CA) on oleic acid (OA)-induced lipid accumulation in HepG2 cells. JBE and CA increased the phosphorylation of AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC) and the expression of carnitine palmitoyl transferase 1a (CPT1a) in OA-treated HepG2 cells. Additionally, these compounds decreased sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and OA-induced lipid accumulation, suggesting that JBE and CA modulate lipid metabolism in HepG2 cells via the AMPK activation pathway.

Effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.

Sinensetin is a rare polymethoxylated flavone found in certain citrus fruits. In this study, we investigated the effects of sinensetin on lipid metabolism in mature 3T3‐L1 adipocytes. Sinensetin decreased the expression of sterol regulatory element‐binding protein 1c (SREBP1c), suggesting its antiadipogeneic property via downreguation of SREBP1c. Also, sinensetin increased the phosphorylation of protein kinase A and hormone‐sensitive lipase, indicating its lipolytic property via a cAMP‐mediated signaling pathway. Moreover, sinensetin inhibited insulin‐stimulated glucose uptake by decreasing the phosphorylation of insulin receptor substrate and Akt. Furthermore, sinensetin increased the phosphorylation of AMP‐activated protein kinase (AMPK) and acetyl‐CoA carboxylase. It also upregulated mRNA expression of carnitine palmitoyltransferase‐1a, suggesting that sinensetin enhances fatty acid β‐oxidation through the AMPK pathway. Taken together, these results suggest that sinensetin may have potential as a natural agent for prevention/improvement of obesity. Copyright

Sinensetin attenuates LPS-induced inflammation by regulating the protein level of IκB-α.

Sinensetin is one of the polymethoxyflavones (PMFs) having five methoxy groups on the basic benzo-γ-pyrone skeleton with a carbonyl group at the C4 position. We investigated in this study the anti-inflammatory activity of sinensetin in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Sinensetin showed anti-inflammatory activity by regulating the protein level of inhibitor κB-α (IκB-α).