Yung-Hsi Kao

Effect of green tea extract on obese women: a randomized, double-blind, placebo-controlled clinical trial.

AIMS To examine the effect of green tea extract (GTE) on obese women and to explore the relationship between GTE and obesity-related hormone peptides. METHODS A randomized, double-blind, placebo-controlled clinical trial was conducted from July 2006 to June 2007 in Taipei Hospital, Taiwan. Seventy-eight of 100 obese women aged between 16 and 60 years with BMI>27 kg/m(2) and who had not received any other weight control maneuvers within the last 3 months completed this study. The subjects were randomly divided into Groups A and B. Group A (n=41) received GTE while Group B (n=37) took cellulose as a placebo, one capsule (400mg) three times each day for 12 weeks. The body weight (BW), body mass index (BMI) and waist circumflex (WC) were measured at the beginning of the study and after 12 weeks of treatment with GTE. The data were compared and expressed as % reduction. RESULTS There was only a 0.3% reduction in BW (0.15 kg) after 12 weeks of treatment with GTE. There was no statistical difference in % reduction in BW, BMI and WC between the GTE and placebo groups. Within group comparison revealed that the GTE group had significant reduction in LDL-cholesterol and triglyceride, and marked increase in the level of HDL-cholesterol, adiponectin and ghrelin. On the other hand, the placebo group showed significant reduction in triglyceride only, and a marked increase in the level of ghrelin alone. CONCLUSIONS This study showed no statistical difference in % reduction in BW, BMI and WC between the GTE and placebo groups after 12 weeks of treatment. The intake of GTE (491 mg catechins containing 302 mg EGCG) for 12 weeks is considered safe as shown by the results.

Green tea: biochemical and biological basis for health benefits.

Publisher Summary Green tea beverages originated many thousands of years ago as a medicinal tonic. The historically long use of many folk remedies does not necessary prove their medical usefulness. However, recent evidence based on modern scientific evaluations of green tea appears to support the possibility that green tea compounds, especially catechins, are medically valuable. The chapter focuses on green tea and green tea catechins rather than on fermented teas or catechin by-products that are produced during fermentation. Theaflavins and thearubigins, a complex mixture of catechin condensation products with a heterogeneous molecular weight distribution, are major fermentation products in black tea, which, like catechins, have antioxidant and antitumorigenic activities. Experimental studies on the physiological effects of some polyphenolic tannins from other plants indicate that they also may be beneficial for decreasing serum lipids, reducing blood pressure, and modulating immune responses and for use as antitumorigenic and antibacterial agents and use in food preservation. The chapter discusses that tea polyphenols are widely used as natural antioxidants for prevention of oxidation of edible oils or discoloring of foods.

Green tea (−)-epigallocatechin gallate inhibits insulin stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor pathway

Insulin and (-)-epigallocatechin gallate (EGCG) have been reported to regulate fat cell mitogenesis and adipogenesis, respectively. This study investigated the pathways involved in EGCG modulation of insulin-stimulated mitogenesis in 3T3-L1 preadipocytes. EGCG inhibited insulin stimulation of preadipocyte proliferation in a dose- and time-dependent manner. EGCG also suppressed insulin-stimulated phosphorylation of the insulin receptor-beta, insulin receptor (IR) substrates 1 and 2 (IRS1 and IRS2), and mitogen-activated protein kinase pathway proteins, RAF1, MEK1/2, and ERK1/2, but not JNK. Furthermore, EGCG inhibited the association of IR with the IRS1 and IRS2 proteins, but not with the IRS4 protein. These data suggest that EGCG selectively affects particular types of IRS and MAPK family members. Generally, EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in modulating insulin-stimulated mitogenic signaling. We identified the EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] in fat cells and found that its expression was sensitive to growth phase, tissue type, and differentiation state. Pretreatment of preadipocytes with 67LR antiserum prevented the effects of EGCG on insulin-stimulated phosphorylation of IRS2, RAF1, and ERK1/2 and insulin-stimulated preadipocyte proliferation (cell number and bromodeoxyuridine incorporation). Moreover, EGCG tended to increase insulin-stimulated associations between the 67LR and IR, IRS1, IRS2, and IRS4 proteins. These data suggest that EGCG mediates anti-insulin signaling in preadipocyte mitogenesis via the 67LR pathway.

The effects of green tea (-)-epigallocatechin-3-gallate on reactive oxygen species in 3T3-L1 preadipocytes and adipocytes depend on the glutathione and 67 kDa laminin receptor pathways.

Green tea (-)-epigallocatechin-3-gallate (EGCG) is known as to regulate obesity and fat cell activity. However, little information is known about the effects of EGCG on oxidative reactive oxygen species (ROS) of fat cells. Using 3T3-L1 preadipocytes and adipocytes, we found that EGCG increased ROS production in dose- and time-dependent manners. The concentration of EGCG that increased ROS levels by 180-500% was approximately 50 muM for a range of 8-16 h of treatment. In contrast, EGCG dose- and time-dependently decreased the amount of intracellular glutathione (GSH) levels. EGCG was more effective than (-)-epicatechin, (-)-epicatechin-3-gallate, and (-)-epigallocatechin in changing ROS and GSH levels. This suggests a catechin-specific effect. To further examine the relation of GSH to ROS as altered by EGCG, we observed that exposure of preadipocytes and adipocytes to N-acetyl-L-cysteine (a GSH precursor) blocked the EGCG-induced increases in ROS levels and decreases in GSH levels. These observations suggest a GSH-dependent effect of EGCG on ROS production. While EGCG was demonstrated to alter levels of ROS and GSH, its signaling was altered by an EGCG receptor (the so-called 67 kDa laminin receptor(67LR)) antiserum, but not by normal rabbit serum. These data suggest that EGCG mediates GSH and ROS levels via the 67LR pathway.

Green tea epigallocatechin gallate inhibits insulin stimulation of adipocyte glucose uptake via the 67-kilodalton laminin receptor and AMP-activated protein kinase pathways.

Insulin and (-)-epigallocatechin gallate (EGCG) are reported to regulate obesity and fat accumulation, respectively. This study investigated the pathways involved in EGCG modulation of insulin-stimulated glucose uptake in 3T3-L1 and C3H10T1/2 adipocytes. EGCG inhibited insulin stimulation of adipocyte glucose uptake in a dose- and time-dependent manner. The concentration of EGCG that decreased insulin-stimulated glucose uptake by 50-60% was approximately 5-10 µM for a period of 2 h. At 10 µM, EGCG and gallic acid were more effective than (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin 3-gallate. We identified the EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] in fat cells and extended the findings for this study to clarify whether EGCG-induced changes in insulin-stimulated glucose uptake in adipocytes could be mediated through the 67LR. Pretreatment of adipocytes with a 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on insulin-increased glucose uptake. This suggests that the 67LR mediates the effect of EGCG on insulin-stimulated glucose uptake in adipocytes. Moreover, pretreatment with an AMP-activated protein kinase (AMPK) inhibitor, such as compound C, but not with a glutathione (GSH) activator, such as N-acetyl-L-cysteine (NAC), blocked the antiinsulin effect of EGCG on adipocyte glucose uptake. These data suggest that EGCG exerts its anti-insulin action on adipocyte glucose uptake via the AMPK, but not the GSH, pathway. The results of this study possibly support that EGCG mediates fat content.

Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways

Resistin is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by sexual hormones. Whether environmental estrogens regulate the production of resistin is still not clear. Using 3T3-L1 adipocytes, we found that octylphenol upregulated resistin mRNA expression in dose- and time-dependent manners. The concentration of octylphenol that increased resistin mRNA levels by 50% was approximately 100 nM within 6 h of treatment. The basal half-life of resistin mRNA induced by actinomycin D was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin mRNA degradation. In addition, octylphenol stimulated resistin protein expression and release. The basal half-life of resistin protein induced by cycloheximide was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin protein degradation. While octylphenol was shown to increase activities of the estrogen receptor (ER) and MEK1, signaling was demonstrated to be blocked by pretreatment with either ICI-182780 (an ERalpha antagonist) or U-0126 (a MEK1 inhibitor), in which both inhibitors prevented octylphenol-stimulated phosphorylation of ERK. These results imply that ERalpha and ERK are necessary for the octylphenol stimulation of resistin mRNA expression. Moreover, U-0126 antagonized the octylphenol-increased resistin protein expression and release. These data suggest that the way octylphenol signaling increases resistin protein levels is similar to that by which it increases resistin mRNA levels; it is likely mediated through an ERK-dependent pathway. In vivo, octylphenol increased adipose resistin mRNA expression and serum resistin and glucose levels, supporting its in vitro effect.

Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid.

Abstract Hamster flank organ growth, as measured by an increase in the area of the pigmented macule, is androgen-dependent. When flank organs of a castrated hamster are treated topically with testosterone, the flank organ becomes larger and darker. Since this growth is known to be dependent on the intracellular active androgen, 5α-dihydrotestosterone (DHT), inhibitors of 5α-reductase which converts testosterone to DHT can inhibit the growth of the flank organ. Certain unsaturated aliphatic fatty acids, such as γ;-linolenic acid and myristoleic acid, as well as other natural compounds, including alizarin and curcumin, are 5·-reductase inhibitors and inhibited flank organ growth. Green tea catechins, including (–)-epicatechin-3-gallate, and (–)-epigallo-catechin-3-gallate (EGCG) are also 5·-reductase inhibitors and inhibited flank organ growth. However, (–)-epicatechin and (–)-epigallocatechin, which are not 5α-reductase inhibitors, also inhibited flank organ growth. EGCG also inhibited DHT-dependent growth of flank organs. These catechins, therefore, may act by a mechanism other than inhibition of 5·-reductase. The effect of EGCG and other compounds was localized at the site of application; they did not affect the growth of the contralateral flank organ in the same animal. Since these compounds do not appear to exhibit systemic effects, they may be potentially useful for treatment of androgen-dependent skin disorders.

Green tea (–)-epigallocatechin gallate inhibits IGF-I and IGF-IIstimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway†

SCOPE This study investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin-like growth factor (IGF)-I-stimulated and IGF-II-stimulated mitogenesis in 3T3-L1 preadipocytes. METHODS AND RESULTS We found that this process was dose and time dependent, and caused by suppression of IGF-I-stimulated and IGF-II-stimulated phosphorylation of p66Shc and mitogen-activated protein kinase (MAPK) pathway proteins, including MEK1 kinase (RAF1), extracellular signal-regulated protein kinase (ERK) kinase (MEK1), and ERK 1 and ERK 2 (ERK1/2), but not phospho-Jun-N-terminal kinase, protein kinase B, p52Shc, or p46Shc. Furthermore, EGCG inhibited the IGF-I-stimulated phosphorylation of the IGF-I receptor-beta (IGF-IR β), the association of IGF-IR with the p66Shc protein, and the IGF-II-stimulated associations of the IGF-II receptor with G(αi-2) and p66Shc proteins, suggesting that EGCG selectively affects particular types of Shc and MAPK family members. Pretreatment with antiserum against the EGCG receptor (also known as the 67-kDa laminin receptor; 67LR), but not with an adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, prevented the inhibitory actions of EGCG on IGF-I- and IGF-II-stimulated ERK1/2 phosphorylation and subsequent preadipocyte proliferation. CONCLUSION The results of this study suggest that EGCG mediates anti-IGF-I and anti-IGF-II signals in preadipocyte mitogenesis via the 67LR but not the AMPK pathway.

Changes in lipolysis and lipogenesis in selected tissues of the landlocked lamprey, Petromyzon marinus, during metamorphosis

This study was designed to examine the biochemical basis of lipid alterations in liver, kidney, and intestine of sea lamprey, Petromyzon marinus, during their nontrophic metamorphosis. Lipolysis, as indicated by triacylglycerol lipase (TGL) activity, increased in liver from larva to stage 6 and in kidney from stage 3 to stage 5, but declined in intestine from stage 3 to stage 5. Fatty acid synthesis and triacylglycerol synthesis were assessed by acetyl-CoA carboxylase (ACC) and diacylglycerol acyltransferase (DGAT) activities, respectively. Acetyl-CoA carboxylase activity decreased in kidney from larva to stage 6 and in liver from stage 3 to stage 6. Diacylglycerol acyltransferase activity in liver increased from larva to stage 5 and in intestine from stage 3 to stage 6, but it was unchanged in kidney. Oxidative metabolism, as estimated by citrate synthase (CS) activity, decreased in liver and intestine from larva to stage 6 and in kidney from larva to stage 3. These data indicate that changes in the activities of TGL, ACC, DGAT, and CS are development-dependent and tissue-specific and suggest that lamprey metamorphosis proceeds in two distinct metabolic phases. The first phase, displayed in larva and stage 3 of metamorphosis, is predominated by lipid depletion from intestine and lipid accumulation in liver and kidney, whereas the second phase, displayed in stage 3 to stage 6, is predominated by lipid depletion from liver and kidney and lipid accumulation in intestine. These biochemical changes may provide the energy required for the pronounced developmental reorganization that occurs during nontrophic metamorphosis of lamprey. J. Exp. Zool. 277:301–312, 1997.

Differences in the total lipid and lipid class composition of larvae and metamorphosing sea lampreys, Petromyzon marinus

This study compared the alterations in total lipid and lipid class composition of kidney, liver, and intestine from sea lamprey, Petromyzon marinus, during their nontrophic metamorphosis with these parameters in unmetamorphosed larvae. Total lipid in kidney and liver initially was higher by 104 and 66%, respectively, in the earliest metamorphic stage (3) examined compared to larvae and then decreased by 73 and 37%, respectively, from stage 3 to stage 7. Total lipid in intestine, on the other hand, was 53% lower at stage 3 compared to larvae and then significantly increased by 260% from stage 3 to stage 7. Large amounts of triacylglycerol (TG) in kidney and liver implicate these organs as lipid depots; much of the change in total lipid content of kidney and liver could be explained by alterations in TG, although significant variations in other lipid classes (e.g., phospholipid, cholesterol) also were noted. These results suggest that lamprey metamorphosis may proceed in two metabolic phases in a tissue-specific manner and that lipid depletion results from specific catabolism of stored TG reserves.