Triglyceride Accumulation In 3T3-L1 Cells Research Articles

Comparative evaluation of Brassica oleracea, Ocimum basilicum, and Moringa oleifera leaf extracts on lipase inhibition and adipogenesis in 3T3-L1 adipocytes.

The anti-adipogenic effects of alcohol extract of Brassica oleracea (BO), Ocimum basilicum (OB), and Moringa oleifera (MO) leaves on 3T3-L1 pre-adipocyte as well as their lipase inhibitory properties were comparatively evaluated. The polyphenol-rich extracts of MO, BO, and OB leaves were profiled for major bioactive compounds using UPLC-HRMS/MS analysis. Among the three plant extracts, BO had the highest flavonoid content with stronger radical scavenging activity. All extracts exhibited lipase inhibitory activities, dose-dependently and a non-competitive type of inhibition with altered kinetic parameters was observed. In cell culture studies, these plant extracts remarkably inhibited the intracellular triglyceride accumulation in 3T3-L1 cells and the effect was in the decreasing order of BO > OB > MO. The extracts also down-regulated the key transcription factors of adipogenesis (PPARγ, C/EPB-α, PI3k, p-Akt, and FAS enzyme) as well as modulated the release profile of leptin and adiponectins. Overall, BO extract showed an exceptional inhibitory potential against both adipogenesis and lipase activities among the evaluated plants. PRACTICAL APPLICATIONS: The present study highlights the anti-adipogenic potential of three local edible plants and herbs, that is, Brassica oleracea (BO), Ocimum basilicum (OB), and Moringa oleifera (MO) leaves, using in vitro models. The results revealed that the BO extract had remarkable activity against adipogenesis in the 3T3-L1 pre-adipocyte differentiation model as well as lipase inhibitory properties. This study elucidates the prospects of natural plant-derived compounds in managing obesity-related health issues. The outcomes of this study would be useful in developing alternative or complementary therapies that are being preferred and largely sought over pharmacological treatments and procedures for controlling and treating abnormal weight gain in humans.

Evaluation of the antidiabetic potential of Psidium guajava L. (Myrtaceae) using assays for α-glucosidase, α-amylase, muscle glucose uptake, liver glucose production, and triglyceride accumulation in adipocytes

Ethnopharmacological relevancePsidium guajava L. (Myrtaceae) leaves are used as an herbal antidiabetic remedy in several parts of the world. On Madagascar, both the bark and leaves are used for treatment of diabetes. Materials and methodsDilution series of ethanolic extracts of P. guajava leaves and bark were used for determining inhibitory activities against yeast α-glucosidase and porcine α-amylase. Skeletal muscle glucose uptake was measured using 2-deoxy-D-(1–3H)-glucose in murine C2C12 skeletal muscle cells. Hepatic glucose-6-phosphatase activity in rat hepatoma H4IIE cells and triglyceride accumulation in murine 3T3-L1 adipocyte-like cells were assessed using Wako AutoKit Glucose assays and AdipoRed reagent, respectively. Cells were incubated for 18 h with the maximal non-toxic concentrations of the plant extracts determined by the lactate dehydrogenase cytotoxicity assay. ResultsEthanolic extracts of P. guajava leaf and bark inhibited α-glucosidase with IC50 values of 1.0 ± 0.3 and 0.5 ± 0.01 μg/mL, respectively. In the α-amylase inhibition assay, the ethanolic extract of bark of P. guajava showed an IC50 value of 10.6 ± 0.4 μg/mL. None of the extracts were able to reduce glucose-6-phosphatase activity in rat hepatoma H4IIE cells. In contrast, P. guajava leaf extract significantly increased 2-deoxy-D-[1–3H]-glucose uptake in C2C12 muscle cells (161.4 ± 10.1%, p = 0.0015) in comparison to the dimethyl sulfoxide (DMSO) vehicle control, as did the reference compounds metformin (144.0 ± 7.7%, p = 0.0345) and insulin (141.5 ± 13.8%, p = 0.0495). Furthermore, P. guajava leaf and bark extracts, as well as the reference compound rosiglitazone, significantly enhanced triglyceride accumulation in 3T3-L1 cells (252.6 ± 14.2%, p < 0.0001, 211.1 ± 12.7%, p < 0.0001, and 201.1 ± 9.2%, p < 0.0001, respectively) to levels higher than the DMSO vehicle control. Moreover, P. guajava leaf extract significantly enhanced the triglyceride accumulation in 3T3-L1 cells compared to rosiglitazone. ConclusionThe results demonstrated that P. guajava leaf and bark extracts can be used as a natural source of α-glucosidase inhibitors. In addition, the bark extract of P. guajava was an effective α-amylase inhibitor. Moreover, P. guajava leaf extract improved glucose uptake in muscle cells, while both leaf and bark extracts enhanced the triglyceride content in adipocytes in culture. P. guajava leaf and bark extracts may thus hypothetically have future applications in the treatment of type 2 diabetes.

An in vitro approach to evaluate the anti-adipogenic effect of Myrica nagi Thunb. Fruit extract on 3T3-L1 adipocyte cell line

BackgroundObesity involves excess accumulation of body fat, leading to metabolic disorders. Although genetic factors involved in obesity have been identified, the influence of phytochemicals on the genes remains to be elucidated. AimsWe aimed to (1) screen extracts of Myrica nagi Thunb. (Myricaceae) by estimating flavonoid, phenol, and tanin content; (2) evaluate enzyme inhibitory activities of the extracts; and (3) analyze the anti-adipogenic activity of the extracts in 3T3L1 cells. MethodsWe evaluated five extracts of M. nagi for their anti-obesity effect by phytochemical screening and enzyme inhibition assays. Furthermore, the extract with the highest inhibitory effect was characterized for its role in adipogenesis using 3T3-L1 cells. ResultsThe methanolic extract of M. nagi (MEMN) showed the highest inhibitory activity against lipase, α-amylase, and α-glucosidase (IC50 values = 91 ± 1.0, 60 ± 4.25, and 100 ± 0.74 μg/mL, respectively). The flavonoid, phenol, and tanin content was highest in the MEMN, with 22.85 ± 1.20, 139.7 ± 11.53, and 1.79 ± 0.12 μg/mL, respectively. The extract also showed anti-oxidant activity with IC50 of 162.22 ± 0.65 μg/mL. Additionally, MEMN did not exert cytotoxicity against 3T3-L1cells; it inhibited adipogenesis and promoted lipolysis of 3T3-L1cells. MEMN at 160 μg/mL concentration reduced triglyceride accumulation in 3T3-L1 cells. Moreover, the extract downregulated PPAR-γ expression. ConclusionsOverall, MEMN possesses potent anti-adipogenic and anti-obesity effects, and thus, can be an alternative herbal treatment for obesity.

Potential Antidiabetic Fumiquinazoline Alkaloids from the Marine-Derived Fungus Scedosporium apiospermum F41-1.

Fumiquinazoline alkaloids have attracted much attention from medicinal and natural product chemists due to their interesting structures and biological potential. In this study, three new and 12 known fumiquinazoline alkaloids were isolated and characterized from the marine fungus Scedosporium apiospermum F41-1. The structures of the new compounds and their absolute configurations were determined using NMR spectroscopy, ECD, and OR calculations. The compounds were evaluated for their antidiabetic potential by determining their triglyceride-promoting activity using 3T3-L1 adipocytes. One of the new compounds, scequinadoline J (14), as well as scequinadolines D (9) and E (10), was found to promote triglyceride accumulation in 3T3-L1 cells. Scequinadoline D (9) demonstrated the most potent activity, with an EC50 value of 0.27 ± 0.03 μM. Quantitative polymerase chain reaction experiments suggested that scequinadoline D (9) acts through activation of the PPARγ pathway. It stimulated the mRNA expression of PPARγ, AMPKα, C/EBPα, LXRα, SCD-1, and FABP4. In addition, its triglyceride-promoting efficacy could be blocked by a double dose of the PPARγ antagonist GW9662. These results indicated that scequinadoline D (9) is a potent insulin sensitizer that targets adipocytes and may be useful for the treatment of type 2 diabetes mellitus after further investigation.

Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

4',6-dimethoxyisoflavone-7-O-β-D-glucopyranoside (wistin) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist that stimulates adipocyte differentiation.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor that directly activates the expression of adipocyte-specific genes, and is universally accepted as the master regulator for adipocyte differentiation. Using a PPARγ luciferase reporter assay system, we showed that 4',6-dimethoxyisoflavone-7-O-β-D-glucopyranoside (wistin) dose-dependently activates PPARγ. Treatment with wistin enhanced the marker of adipocyte differentiation, such as triglyceride accumulation in 3T3-L1 cells. Real-time quantitative polymerase chain reaction showed that wistin increased the expression of PPARγ2 messenger RNA. Moreover, the addition of wistin upregulated the expression of PPARγ-target genes, aP2 and adiponectin in 3T3-L1 cells. To our knowledge, wistin is the first isoflavonoid O-glycoside that exhibits PPARγ agonist activity.

Effects of high glucose on caveolin-1 and insulin signaling in 3T3-L1 adipocytes

ABSTRACTAdipocytes exposed to high glucose concentrations exhibit impaired metabolic function, including an increase of oxidative and proinflammatory factors that might favor the development of insulin resistance. Caveolin-1 (Cav-1) is a key mediator of the insulin transduction pathway whose expression is significantly enhanced during adipocyte differentiation. In this work, we studied the effects of high glucose concentration on the regulation of Cav-1 expression and activation and its relation to the insulin signaling pathway during the adipogenic process and in long-term differentiated adipocytes. Both, long-term high glucose exposure during adipogenesis and short-term glucose incubation of mature adipocytes, promoted triglyceride accumulation in 3T3-L1 cells. The short-term exposure of mature adipocytes to high glucose significantly reduced the sensitivity to insulin of Cav-1, insulin receptor (IR) and potein kinase B (AKT-2) phosphorylation, as well as insulin-induced deoxyglucose uptake. Adipocytes differentiated in the presence of high glucose lost Cav-1 and IR response to insulin-stimulated phosphorylation, but maintained the insulin sensitivity of AKT-2 phosphorylation and deoxyglucose uptake. Although long-term high glucose exposure increased DNA methylation in Cav-1 promoter, Cav-1 expression was not affected. Moreover, these cells showed an increase of Cav-1, IR and AKT-2 protein content, pointing to an adaptive response induced by the long-term high glucose exposure.

Sea cucumber and blue mussel: new sources of phospholipid enriched omega-3 fatty acids with a potential role in 3T3-L1 adipocyte metabolism.

Omega (n)-3 polyunsaturated fatty acids (PUFA), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to reduce the risk of insulin resistance and ameliorate obesity-associated disorders. DHA and EPA structured in the phospholipid form possess superior biological effects compared to the triglyceride form available in fish oil. In this study, we have found that sea cucumber (SC) and blue mussel (BM) from Newfoundland and Labrador are rich sources of n-3 PUFA structured in the phospholipid form. Treatment with SC and BM methanolic extracts (250 and 100 μg mL(-1), respectively) significantly (p < 0.01) increased triglyceride accumulation in 3T3-L1 adipocytes, along with an increase in the mRNA expression of the peroxisome proliferator-activated receptor-γ (37 and 39%, respectively) and adiponectin (57 and 56%, respectively) compared with control cells (p < 0.05). Only SC extracts (250 μg mL(-1)) increased the mRNA expression of sterol regulatory element-binding protein-1 (SREBP-1). Treatment with higher concentrations of SC and BM extracts (500 and 750 μg mL(-1), respectively) significantly (p < 0.01) decreased triglyceride accumulation in 3T3-L1 cells as opposed to an increase in triglyceride accumulation at lower concentrations. This was due to inhibition of acetyl-CoA carboxylase-1 and SREBP-1 mRNA expression compared to control cells (p < 0.05). There was no effect of the extracts on the mRNA expression of hormone sensitive lipase or lipolysis, suggesting that the decrease in triglyceride accumulation at higher concentrations is not due to breakdown and release of fat. This is the first report to show that SC and BM are new sources of phospholipid bonded n-3 PUFA, with the potential to target insulin resistance and obesity.

Inhibitory effect of chemical constituents from Artemisia scoparia Waldst. et Kit. on triglyceride accumulation in 3T3-L1 cells and nitric oxide production in RAW 264.7 cells

We investigated the anti-obesity effect of the aerial part of Artemisia scoparia Waldst. et Kit. (Compositae). An 80 % aqueous EtOH extract of the aerial part inhibited triglyceride (TG) accumulation and the nitric oxide (NO) production activity. A new chromane derivative was isolated from the aerial part of A. scoparia Waldst. et Kit. along with 18 known compounds. The structure of the new chromane, scopariachromane (1), was elucidated by spectroscopic analyses. The inhibitory effects of the compounds on TG accumulation activity were examined. Among these, cirsiliol (11) inhibited TG accumulation in 3T3-L1 preadipocytes. Jaceosidin (12) inhibited NO production in a murine macrophage-like cell line (RAW 264.7). These results indicate that the 80 % aqueous EtOH extract and compounds isolated from the aerial part of A. scoparia Waldst. et Kit. may improve obesity-related insulin resistance.

Platycodin D inhibits adipogenesis of 3T3‐L1 cells by modulating kruppel‐like factor 2 and peroxisome proliferator‐activated receptor γ

In this study, platycodin D was found to inhibit intracellular triglyceride accumulation in 3T3-L1 cells with an IC(50) of 7.1 microM. The expression levels of genes involved in lipid metabolism such as fatty-acid-binding protein 4 and lipoprotein lipase were significantly downregulated following treatment with platycodin D. Treatment with platycodin D also resulted in a reduction of Peroxisome proliferator-activated receptor(PPAR)gamma expression and its binding to target DNA sequence. Among the various upstream regulators of PPARgamma, the expression of Kruppel-like factor(KLF)2, an anti-adipogenic factor, was significantly upregulated following platycodin D treatment. When the upregulation of KLF2 was inhibited by KLF2 siRNA, the expression and binding of PPARgamma to its target sequence were significantly recovered under these conditions. The results of this study suggested that anti-adipogenic effect of platycodin D involves the upregulation of KLF2 and subsequent downregulation of PPARgamma.

Effect of trans8, cis10+cis9, trans11 Conjugated Linoleic Acid Mixture on Lipid Metabolism in 3T3‐L1 Cells

Evidence suggests that minor isomers of conjugated linoleic acid (CLA), such as trans8, cis10 CLA, can elicit unique biological effects of their own. In order to determine the effect of a mixture of t8, c10+c9, t11 CLA isomers on selected aspects of lipid metabolism, 3T3-L1 preadipocytes were differentiated for 8 days in the presence of 100 microM linoleic acid (LA); t8, c10+c9, t11 CLA; t10, c12+c9, t11 CLA or purified c9, t11 CLA. Whereas supplementation with c9, t11 and t10, c12+c9, t11 CLA resulted in cellular triglyceride (TG) concentrations of 3.4 +/- 0.26 and 1.3 +/- 0.11 microg TG/microg protein, respectively (P < 0.05), TG accumulation following treatment with CLA mixture t8, c10+c9, t11 was significantly intermediate (2.5 +/- 0.22 microg TG/microg protein, P < 0.05) between the two other CLA treatments. However, these effects were not attributable to an alteration of the Delta(9) desaturation index. Adiponectin content of adipocytes treated with t8, c10+c9, t11 mixture was similar to the individual isomer c9, t11 CLA, and both the t8, c10+c9, t11 and c9, t11 CLA groups were greater (P < 0.05) than in the t10, c12+c9, t11 CLA group. Overall, these results suggest that t8, c10+c9, t11 CLA mixture affects TG accumulation in 3T3-L1 cells differently from the c9, t11 and t10, c12 isomers. Furthermore, the reductions in TG accumulation occur without adversely affecting the adiponectin content of these cells.

Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals

Human adenovirus-36 (Ad-36) increases adiposity in chickens, mice, and nonhuman primates and is associated with human obesity. Ad-36 paradoxically reduces serum cholesterol and triglycerides in animal models. Ad-36 increases adipocyte differentiation and triglyceride accumulation in 3T3-L1 cells in vitro. This study evaluated whether three other human adenoviruses increase adiposity in chickens and in 3T3-L1 cells in vitro. We inoculated chickens with human Ad-2, Ad-31, Ad-37, or media at age 3 wk. Food intake and weights were recorded for 3.5 wk, and then chickens were killed and visceral fat, body composition, serum lipids, and viral antibody status were determined. Visceral fat and total body fat were significantly elevated (P < 0.001) in the Ad-37 group compared with all other groups. Final body weights were higher in chickens inoculated with Ad-37 compared with Ad-2, but not significantly higher than in control or Ad-31 groups. Food intake did not differ among groups. Serum cholesterol was elevated in Ad-37 chickens compared with control (P < 0.01) but was not affected by other viruses. Triglycerides were reduced in Ad-37 chickens (P < 0.0001) but were not affected by other viruses. In 3T3-L1 cells in vitro, Ad-31, Ad-36, and Ad-37, but not Ad-2, increased adipocyte differentiation and triglycerides accumulation. In summary, Ad-37 is another human adenovirus that increases adiposity and reduces serum triglycerides in an animal model. However, the response of serum cholesterol is opposite that of Ad-36. Evaluation of other human adenoviruses to determine their effects on adiposity and serum lipids is warranted, but in vitro assays may not be definitive for this purpose.

Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid β-oxidation and glucose

Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype observed in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the molecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity is still poorly understood. Here, we found that preadipocytes incubated with inhibitors of mitochondrial respiration such as antimycin A (AA) accumulate TG vesicles but do not acquire specific markers of adipocytes. Although the uptake of TG precursors is not stimulated in 3T3-L1 cells with impaired mitochondrial activity, we found a strong stimulation of glucose uptake in AA-treated cells mediated by calcium and phosphatidylinositol 3-kinase/Akt1/glycogen synthase kinase 3beta, a pathway known to trigger the translocation of glucose transporter 4 to the plasma membrane in response to insulin. TG accumulation in AA-treated cells is mediated by a reduced peroxisome proliferator-activated receptor gamma activity that downregulates muscle carnitine palmitoyl transferase-1 expression and fatty acid beta-oxidation, and by a direct conversion of glucose into TGs accompanied by the activation of carbohydrate-responsive element binding protein, a lipogenic transcription factor. Taken together, these results could explain how mitochondrial impairment leads to the multivesicular phenotype found in some mitochondria-originating diseases associated with a dysfunction in fat metabolism.

Synthesis and Biological Activity of Novel Substituted Pyridines and Purines Containing 2,4‐Thiazolidinedione.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and biological activity of novel substituted pyridines and purines containing 2,4-thiazolidinedione

A series of substituted pyridines and purines containing 2,4-thiazolidinedione were designed and synthesized from their corresponding pyridines and purines. These synthesized compounds (entry no. 6a–d, 12a–e, 18a–d, 23a–c) were evaluated for their effect on triglyceride accumulation in 3T3-L1 cells in vitro and their hypoglycemic and hypolipidemic activity in the genetically diabetic KKA y mice in vivo. On the basis of their biological activities, 5-(4-{2-[ N-methyl-(5-phenyl-pyridin-2-yl)amino]ethoxy}benzyl)thiazolidine-2,4-dione ( 6d) was selected as a candidate for further pharmacological studies.

Inhibitory effect of natural phenolic lipids upon NAD-dependent dehydrogenases and on triglyceride accumulation in 3T3-L1 cells in culture.

Alkylresorcinols are phenolic lipids present at levels of 0.03-0.15% in wheat and rye grains and almost 10 times higher in respective bran products. Despite numerous studies on the influence of dietary fibers on the regulation of energy metabolism, this issue still remains controversial. The objective of our current studies was to investigate whether 5-n-alk(en)ylresorcinols, natural phenolic components of high fiber human diets, may be considered as natural regulators of excessive fat accumulation. Our studies revealed that 5-n-alk(en)ylresorcinols isolated from wheat and rye bran inhibit glycerol-3-phosphate dehydrogenase, the key enzyme in triglyceride synthesis in adipocytes, specifically and effectively. Further in vitro studies showed that these compounds also prevent triglyceride accumulation in 3T3-L1 cells. The most effective compound in both systems was 5-n-heneicosylresorcinol. The results indicate that the potential to prevent triglyceride accumulation increases with the hydrophobicity of the phenolic inhibitor.

Effect of sterols and fatty acids on growth and triglyceride accumulation in 3T3-L1 cells

Epidemiologic studies suggest a role of dietary fat in the development of obesity. Populations that consume Western diets have a higher incidence of obesity than do those that consume a vegetarian type diet such as Asians. Because dietary fats are made up mostly of triglyceride with minor lipids such as sterols, the objective of this study was to examine the effect of different fatty acids, the main component of triglycerides, and sterols on cell growth and triglyceride accumulation in 3T3-L1 cells. These cells are being used as an in vitro model for studying obesity because upon differentiation in culture they accumulate triglycerides. Cells were seeded at 5,000 cells/cm 2 and supplemented with 0, 3, 10, or 30 μM of oleic acid, elaidic acid, or docosahexaenoic acid (DHA). Similarly, cells were supplemented with 0, 2, 8, or 16 μM of cholesterol, β-sitosterol (SIT), or campesterol. Cell growth was measured by cell counting. Cellular triglycerides were measured by the Oil Red O method. In some experiments, fatty acids were combined with sterols and growth and triglyceride content were assessed as described. Both DHA and SIT had inhibitory effects on 3T3-L1 cell growth. However, SIT was more potent than DHA in this regard. The combination of SIT and oleic acid was the most potent in inhibiting cell growth and increasing cellular triglyceride content. It is concluded that cell growth and triglyceride accumulation in 3T3-L1 cells is influenced by fatty acid and sterols. When used alone, DHA and SIT inhibit cell growth. SIT was more effective in this process than was DHA. There was an interaction between fatty acids and sterols. The most effective combination inhibiting cell growth and triglyceride concentration was the combination of SIT and oleic acid. This combination reduced cell growth and increased triglyceride accumulation. These data suggest that diets rich in both monounsaturated fatty acids and phytosterols may play a role in controlling obesity.

Isolation and identification of acetyl-CoA carboxylase inhibitors from green tea (Camellia sinensis).

An aqueous methanol extract from green tea showed potent acetyl-CoA carboxylase inhibitory activity. An active compound was isolated from the extract and identified as (-)-epigallocatechin gallate by instrumental analyses. The IC50 value of (-)-epigallocatechin gallate was 3.1 x 10(-4) M. Among tea catechins and related compounds, nearly equal activity was found in (-)-epigallocatechin gallate and (-)-epicatechin gallate, whereas (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, gallic acid and methyl gallate each had no inhibitory activity. These results indicate that the 3-O-gallate group of the catechin structure was necessary for this activity. (-)-Epigallocatechin gallate inhibited triglyceride accumulation in 3T3-L1 cells at a concentration of 1.0 x 10(-7) M or higher.

Adipostatins A and B, new inhibitors of glycerol-3-phosphate dehydrogenase.

As a result of screening for inhibitors of glycerol-3-phosphate dehydrogenase, which may be effective to prevent corpulence, we isolated two inhibitors named adipostatin A and adipostatin B from the culture broth of Streptomyces cyaneus 2299-SV1. Their structures have been established to be 5-n-pentadecylresorcinol and 5-isopentadecylresorcinol, respectively. Adipostatin A and adipostatin B inhibited glycerol-3-phosphate dehydrogenase at the IC50 values of 4.1 microM and 4.5 microM, respectively. These compounds prevented triglyceride accumulation in 3T3-L1 cells at a concentration of the microM level.