Effects of Purified Vitexin and Iso-Vitexin from Mung Bean Seed Coat on Antihyperglycemic Activity and Gut Microbiota in Overweight Individuals' Modulation.

Exceeding a healthy weight significantly elevates the likelihood of developing type 2 diabetes (T2DM). A commercially available singular constituent, available as either purified vitexin or iso-vitexin, has been associated with a decreased risk of T2DM, but its synergistic effect has not been reported yet. Vitexin and iso-vitexin were extracted using an ethanol-based solvent from mung bean seed coat (MBCE) and subsequently purified using preparative liquid chromatography (Prep-LC). Eleven mixture ratios of vitexin and/or iso-vitexin were determined for their antioxidant and antihyperglycemic activities. The 1:1.5 ratio of vitexin to iso-vitexin from MBCE demonstrated the most synergistic effects for enzyme inhibition and glucose uptake in HepG2 cells within an insulin-resistant system, while these ratios exhibited a significantly lower antioxidant capacity than that of each individual component. In a gut model system, the ratio of 1:1.5 (vitexin and iso-vitexin) regulated the gut microbiota composition in overweight individuals by decreasing the growth of Enterobacteriaceae and Enterococcaceae, while increasing in Ruminococcaceae and Lachnospiraceae. The application of vitexin/iso-vitexin for 24 h fermentation enhanced a high variety of abundances of 21 genera resulting in five genera of Parabacteroides, Ruminococcus, Roseburia, Enterocloster, and Peptacetobacter, which belonged to the phylum Firmicutes, exhibiting high abundant changes of more than 5%. Only two genera of Proteus and Butyricicoccus belonging to Proteobacteria and Firmicutes decreased. The findings suggest that these phytochemicals interactions could have synergistic effects in regulating glycemia, through changes in antihyperglycemic activity and in the gut microbiota in overweight individuals. This optimal ratio can be utilized by industries to formulate more potent functional ingredients for functional foods and to create nutraceutical supplements aimed at reducing the risk of T2DM in overweight individuals.

Effects of Omega-3 Supplementation on the Delayed Onset Muscle Soreness after Cycling High Intensity Interval Training in Overweight or Obese Males.

People with overweight or obesity preferred high-intensity interval training (HIIT) due to the time-efficiency and pleasure. However, HIIT leads to delayed onset muscle soreness (DOMS). The present study aimed to investigate the effects of omega-3 supplementation on DOMS, muscle damage, and acute inflammatory markers induced by cycling HIIT in untrained males with overweight or obesity. A randomized, double-blinded study was used in the present study. Twenty-four males with a sedentary lifestyle were randomly assigned to either receive omega-3 (O3) (4 g fish oil) or placebo (Con). Subjects consumed the capsules for 4 weeks and performed cycling HIIT at the 4th week. After 4 weeks-intervention, the omega-3 index of O3 group increased by 52.51% compared to the baseline. All subjects performed HIIT at 4th week. The plasma creatine kinase (CK) level of Con group increased throughout 48h after HIIT. While the CK level of O3 group increased only immediately and 24h after HIIT and decreased at 48h after HIIT. The white blood cell count (WBC) of Con group increased immediately after the HIIT, while O3 group did not show such increase. There was no change of CRP in both groups. O3 group had a higher reduction of calf pain score compared to Con group. O3 group also showed a recovery of leg strength faster than Con group. Omega-3 supplementation for 4 weeks lower increased CK level, reduced calf pain score, and recovery leg strength, DOMS markers after cycling HIIT.

Potential Health Benefits of Fermented Vegetables with Additions of Lacticaseibacillus rhamnosus GG and Polyphenol Vitexin Based on Their Antioxidant Properties and Prohealth Profiles.

Fermented vegetables are increasingly being recognized as an important dietary component, particularly of plant-based diets, to achieve a sustainable healthy gut because of their microbial diversity and antioxidant properties. However, the functional relevance of fermented vegetables varies based on the raw ingredients used and nutrient supplementation. Therefore, in the present study, we investigated the microbial diversity and antioxidant activity of three formulas of fermented vegetables (standard, supplemented with Lacticaseibacillus rhamnosus GG, and supplemented with polyphenol vitexin) at days 0 and 15. The bacterial community profiles were determined through 16S rRNA sequencing analysis, and antioxidant activity was analyzed using 2,2-diphenyl-1-picrylhydrazyl and by measuring the oxygen radical absorbance capacity, the ferric reducing ability of plasma, and the total phenolic content. The results confirm microbial diversity in the taxonomic composition of the different formulas of fermented vegetables, with different bacteria predominating, particularly lactic acid bacteria including the genera Weissella, Pedicocccus, Leuconostoc, and Lactobacillus. Spearman's correlation analysis showed significant differences in the specific bacteria present in the different formulas of fermented vegetables that conferred antioxidant capacity. Our findings show that supplementation with L. rhamnosus GG and polyphenol vitexin may effectively enhance the functional relevance of foods by promoting cellular protection against oxidative stress.

Effect of Yogurt Ice Cream on the Viability and Antidiabetic Potential of the Probiotics Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, and Bifidobacterium animalis subsp. lactis after In Vitro Digestion.

Probiotics can ameliorate type 2 diabetes mellitus (T2DM) via several mechanisms such as by decreasing inflammatory cytokines and increasing pancreatic ß-cell functions. Another targeted mechanism for managing T2DM involves inhibiting α-amylase and α-glucosidase, which exhibit antioxidant activity and affect carbohydrate metabolism by delaying carbohydrate digestion, thus mitigating glucose in the circulation. Dairy products are effective matrices for delivering probiotics through the gastrointestinal tract. We compared the viability and antioxidant activity of the probiotics Lactobacillus acidophilus LA-5, Lacticaseibacillus rhamnosus GG, and Bifidobacterium animalis subsp. lactis in yogurt ice cream after in vitro digestion and compared α-amylase and α-glucosidase inhibition activities. Lacticaseibacillus rhamnosus GG had the highest viability after in vitro digestion (oral, gastric, and intestinal). Lactobacillus acidophilus LA-5 and Lacticaseibacillus rhamnosus GG exhibited the highest percentages of α-glucosidase (16.37% ± 0.32%) and α-amylase (41.37% ± 0.61%) inhibition. Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus acidophilus LA-5 showed the highest antioxidant activities via the α,α-diphenyl-ß-picrylhydrazyl free radical-scavenging method and ferric-reducing antioxidant power assay, respectively. These findings suggest that yogurt ice cream can provide a suitable matrix for the delivery of probiotics from dairy culture to promote intestinal homeostasis with probiotic benefits in the host as well as a potential functional food to help reduce postprandial hyperglycaemia.

Polymeric Packaging Applications for Seafood Products: Packaging-Deterioration Relevance, Technology and Trends.

Seafood is a highly economical product worldwide. Primary modes of deterioration include autolysis, oxidation of protein and lipids, formation of biogenic amines and melanosis, and microbial deterioration. These post-harvest losses can be properly handled if the appropriate packaging technology has been applied. Therefore, it is necessary for packaging deterioration relevance to be clearly understood. This review demonstrates recent polymeric packaging technology for seafood products. Relationship between packaging and quality deterioration, including microbial growth and chemical and biochemical reactions, are discussed. Recent technology and trends in the development of seafood packaging are demonstrated by recent research articles and patents. Development of functional polymers for active packaging is the largest area for seafood applications. Intelligent packaging, modified atmosphere packaging, thermal insulator cartons, as well as the method of removing a fishy aroma have been widely developed and patented to solve the specific and comprehensive quality issues in seafood products. Many active antioxidant and antimicrobial compounds have been found and successfully incorporated with polymers to preserve the quality and monitor the fish freshness. A thermal insulator has also been developed for seafood packaging to preserve its freshness and avoid deterioration by microbial growth and enzymatic activity. Moreover, the enhanced biodegradable tray is also innovative as a single or bulk fish container for marketing and distribution. Accordingly, this review shows emerging polymeric packaging technology for seafood products and the relevance between packaging and seafood qualities.

Gut Microbiota Modulation, Anti-Diabetic and Anti-Inflammatory Properties of Polyphenol Extract from Mung Bean Seed Coat (Vigna radiata L.).

The present study investigated the gut health, anti-diabetic, and anti-inflammatory activities of mung bean seed coat extract (MSE). MSE was obtained by pressurized liquid extraction (PLE) using 50% ethanol as the extracting solvent. After 24 h of in vitro human fecal fermentation, MSE exhibited higher productions of total short-chain fatty acids (SCFA) than those of the control group (CON) and other polyphenol-rich substrates, including gallic acid (GA) and vitexin (VIT) (p > 0.05), but still lower than the fructo-oligosaccharide (FOS). In 16S-rRNA next-generation sequencing, MSE regulated the composition of gut microbiota by stimulating the growth of the beneficial bacteria Enterococcus, Ruminococcus, Blautia, and Bacteroides and decreasing the growth of the potential pathogenic bacteria Escherichia-Shigella. Similarly, qPCR showed increased numbers of Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii, and Prevotella, compared with those of CON (p < 0.05). MSE also reduced reactive oxygen species and increased glucose uptake in insulin-resistant HepG2 cells dose-dependently. The anti-inflammatory activity of MSE was observed in LPS-stimulated THP-1 monocytes with the reduction of TNFα, IL-1ß, IL-6, and IL-8 genes. The data demonstrated the potential applications of MSE as a dietary supplement with gut health benefits and its ability to mitigate diabetes and inflammatory-related diseases.

Effect of chicken manure and chemical fertilizer on the yield and qualities of white mugwort at dissimilar harvesting times.

One of the key components that affects soil productiveness, plant growth, and crop quality is fertilization. The effect of fertilizer, both organic and chemical, on the extremely acidic (pH 4.10) sandy loam soil chemical properties, yield, and quality of white mugwort grown were evaluated in this study. The field experiment arranged in a randomized complete block design, with four replications was conducted in Prachin Buri province, Thailand. There were six treatments, no fertilization (control), chemical fertilizer (25-7-7 + 46-0-0) applied at 187.50 (66.56 N:6.77 P2O5:6.77 K2O kg ha-1) kg ha-1 and applied at 375.00 (133.12 N:13.13 P2O5:13.13 K2O kg ha-1) kg ha-1, chicken manure applied at 3.36, 6.72, and 10.08 t ha-1. After harvesting, application of chicken manure tended to increase soil organic matter compared to the control, however, the application of chemical fertilizer did not show the same effect. The fresh weight of white mugwort increased with the rise in both fertilizer levels. Chicken manure application at 10.08 t ha-1 produced the highest fresh weight at all times. The level of accumulated nitrate was significantly greater when fertilizer rates increased. In addition, the total phenolic content of the white mugwort fertilized with chicken manure was higher than that fertilized with chemical fertilizer. However, there was no association between the DPPH radical scavenging capacity at harvesting times and different fertilization. Based on the results, chicken manure applied at 10.08 t ha-1 gave the best yield and higher total phenolic content of white mugwort, which was probably due to the improved soil organic matter.

Extraction of Phenolic and Flavonoid Compounds from Mung Bean (Vigna radiata L.) Seed Coat by Pressurized Liquid Extraction.

Mung bean seed coat (MBC) is a by-product of the mung bean processing industry. It contains a large number of phenolic compounds with therapeutic anti-inflammatory, anti-diabetic and antioxidant properties. This research aimed to investigate the optimum conditions for phenolic and flavonoid extraction from MBC by pressurized liquid extraction (PLE). Response surface methodology (RSM) was used to study the effects of temperature (80-160 °C), pressure (1200-1800 psi) and ethanol concentration (5-95%) on total phenolic content (TPC), total flavonoid content (TFC) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity (ABTS). Scale-up extraction was also performed. The optimum conditions for extraction were 160 °C, 1300 psi and 50% ethanol. Under optimum conditions, the TPC was 55.27 ± 1.14 mg gallic acid equivalent (GAE)/g MBC, TFC was 34.04 ± 0.72 mg catechin equivalent (CE)/g MBC and ABTS scavenging activity was 195.05 ± 2.29 mg trolox equivalent (TE)/g MBC. The TFC and ABTS scavenging activity of the extracts obtained at the pilot scale (10 L) was not significantly different from the laboratory scale, while TPC was significantly increased. The freeze-dried MBC extract contained vitexin and isovitexin 130.53 ± 17.89, 21.21 ± 3.22 mg/g extract, respectively. In conclusion, PLE was able to extract phenolics, flavonoids with ABTS scavenging activity from MBC with the prospect for future scale-up for food industry.

Comparative Investigation of Combined Metabolomics-Flavoromics during the Ripening of Mango (Mangifera indica L.) cv. 'Nam Dok Mai Si Thong' and 'Nam Dok Mai No. 4'.

A metabolomics-flavoromics approach was conducted to assess the micromolecules of 'Nam Dok Mai Si Thong' and 'Nam Dok Mai No. 4' mango cultivars from two seasons. During ripening, FAMEs, FFAs, fatty alcohols, sterols, and organic acids were dominant at 0-2 days, whereas amino acids, sugars, and volatile organic compounds, including esters, alcohols, ketones, aldehydes, and terpenes, were at higher levels at 4-8 days. Nine metabolites (palmitic/linoleic/linolenic/citric/malic acids, ß-sitosterol, sucrose, glycine, and leucine) and two volatile organic compounds (ethyl octanoate/decanoate) were related to ripening-associated changes within eight days. During ripening, sucrose at 6-8 days, citric/malic acid at 0-2 days, glycine and leucine at 4 days, and ethyl octanoate and ethyl decanoate at 8 days could be used as quality biomarkers for Nam Dok Mai Si Thong; palmitic/linoleic/linolenic acids at 0 days and ß-sitosterol at 0-4 days could be used as quality biomarkers for Nam Dok Mai No. 4.

Water Extract of Mungbean (Vigna radiata L.) Inhibits Protein Tyrosine Phosphatase-1B in Insulin-Resistant HepG2 Cells.

The present study aimed to investigate the effects of mungbean water extract (MWE) on insulin downstream signaling in insulin-resistant HepG2 cells. Whole seed mungbean was extracted using boiling water, mimicking a traditional cooking method. Vitexin and isovitexin were identified in MWE. The results showed that MWE inhibited protein tyrosine phosphatase (PTP)-1B (IC50 = 10 µg/mL), a negative regulator of insulin signaling. MWE enhanced cellular glucose uptake and altered expression of genes involved in glucose metabolism, including forkhead box O1 (FOXO1), phosphoenolpyruvate carboxykinase (PEPCK), and glycogen synthase kinase (GSK)-3ß in the insulin-resistant HepG2 cells. In addition, MWE inhibited both α-amylase (IC50 = 36.65 mg/mL) and α-glucosidase (IC50 = 3.07 mg/mL). MWE also inhibited the formation of advanced glycation end products (AGEs) (IC50 = 2.28 mg/mL). This is the first study to show that mungbean water extract increased cellular glucose uptake and improved insulin sensitivity of insulin-resistant HepG2 cells through PTP-1B inhibition and modulating the expression of genes related to glucose metabolism. This suggests that mungbean water extract has the potential to be a functional ingredient for diabetes.

Mungbean seed coat water extract inhibits inflammation in LPS-induced acute liver injury mice and LPS-stimulated RAW 246.7 macrophages via the inhibition of TAK1/IκBα/NF-κB.

Inflammation plays an important role in pathogenesis and progression of many chronic diseases. Although, anti-inflammatory activities of mungbean have been suggested, the underlying mechanism have not been fully understood. The present study aimed to reveal the anti-inflammatory effects of mungbean seed coat water extract (MSWE) in lipopolysaccharide (LPS)-stimulated inflammation in RAW 246.7 macrophages and LPS-induced acute liver injury mice. MSWE pretreatment downregulated the elevated expression of inflammatory markers induced by LPS in the transcriptional and protein level. MSWE inhibited NF-κB activation through the suppression of phosphorylated p65 subunit, IκBα degradation, and transforming growth factor-ß-activated kinases 1 (TAK1) phosphorylation in LPS-stimulated RAW 246.7 cells. Vitexin, the major flavonoid in MSWE showed similar effects. In in vivo experiments, we found that oral administration of MSWE downregulated iNOS expression in LPS-induced acute liver injury mice. The mRNA expression of inflammatory markers and macrophage infiltration was also decreased in the livers. Collectively, MSWE exerts anti-inflammatory role, in part possibly through its active compound vitexin, by inhibiting NF-κB activation via inhibition of TAK1 phosphorylation and IκBα degradation. This suggests that MSWE is beneficial to combat various inflammatory diseases.

Mitigation of nonalcoholic fatty liver disease in high-fat-fed mice by the combination of decaffeinated green tea extract and voluntary exercise.

We have shown that combination treatment with decaffeinated green tea extract (GTE) and voluntary exercise (Ex) reduces obesity and insulin resistance in high-fat (HF)-fed mice to a greater extent than either treatment alone. Here, we investigated the effects of GTE-, Ex- or the combination on the development of obesity-related NAFLD. Male C57BL/6 J mice were treated for 16 weeks with HF diet (60% energy from fat), HF supplemented with 7.7 g GTE/kg, HF plus access to a voluntary running wheel, or the combination. We found that treatment of mice with the combination mitigated the development of HF-induced NAFLD to a greater extent than either treatment alone. Combination-treated mice had lower plasma alanine aminotransferase (92% lower) and hepatic lipid accumulation (80% lower) than HF-fed controls: the effect of the single treatments was less significant. Mitigation of NAFLD was associated with higher fecal lipid and nitrogen levels. Combination treated, but not singly treated mice, had higher hepatic expression of genes related to mitochondrial biogenesis (sirtuin 1 [59%]; peroxisome proliferator-activated receptor γ coactivator 1α [42%]; nuclear respiratory factor 1 [38%]; and transcription factor B1, mitochondrial [89%]) compared to the HF-fed controls. GTE-, Ex-, and the combination-treatment groups also had higher hepatic expression of genes related to cholesterol synthesis and uptake, but the combination was not better than the single treatments. Our results suggest the combination of GTE and Ex can effectively mitigate NAFLD. Future studies should determine if the combination is additive or synergistic compared to the single treatments.

Fibroblast Growth Factor 21 (Fgf21) Gene Expression Is Elevated in the Liver of Mice Fed a High-Carbohydrate Liquid Diet and Attenuated by a Lipid Emulsion but Is Not Upregulated in the Liver of Mice Fed a High-Fat Obesogenic Diet.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. OBJECTIVE: We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. METHODS: C57BL/6 male mice were fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either 4% or 13.5% of energy for 5 wk (Expt. 1) or 1 wk (Expt. 2). In Expt. 3, mice were fed a purified LFD (∼10% fat) or HFD (∼60% fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. RESULTS: Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5- to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+exercise group to <20% of the level in the HFD group (P < 0.0001). CONCLUSIONS: In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake.

Dietary γ-Tocopherol-Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response, and PPARγ.

This study evaluated the anticancer activity and mechanism of action of a γ-tocopherol-rich tocopherol mixture, γ-TmT, in two different animal models of estrogen-induced breast cancer. The chemopreventive effect of γ-TmT at early (6 weeks), intermediate (18 weeks), and late (31 weeks) stages of mammary tumorigenesis was determined using the August-Copenhagen Irish rat model. Female rats receiving 17ß-estradiol (E2) implants were administered with different doses (0%, 0.05%, 0.1%, 0.3%, and 0.5%) of γ-TmT diet. Treatment with 0.3% and 0.5% γ-TmT decreased tumor volume and multiplicity. At 31 weeks, serum concentrations of E2 were significantly decreased by γ-TmT. γ-TmT preferentially induced expression of the E2-metabolizing enzyme CYP1A1, over CYP1B1 in the rat mammary tissues. Nrf2-dependent antioxidant response was stimulated by γ-TmT, as evident from enhanced expression of its downstream targets, NQO1, GCLM, and HMOX1. Serum concentrations of the oxidative stress marker, 8-isoprostane, were also decreased in the γ-TmT-treated groups. Treatment with γ-TmT increased expression of PPARγ and its downstream genes, PTEN and p27, whereas the cell proliferation marker, PCNA, was significantly reduced in γ-TmT-treated mammary tumors. In an orthotopic model in which human MCF-7 breast cancer cells were injected into the mammary fat pad of immunodeficient mice, γ-TmT inhibited E2-dependent tumor growth at all the doses tested. In conclusion, γ-TmT reduced mammary tumor development, in part through decreased E2 availability and reduced oxidative stress in mammary tissues; γ-TmT could thus be an effective agent for the prevention and treatment of E2-induced breast cancer.

Decaffeinated Green Tea and Voluntary Exercise Induce Gene Changes Related to Beige Adipocyte Formation in High Fat-Fed Obese Mice.

We have previously reported that decaffeinated green tea extract (GTE) in combination with voluntary exercise (Ex) reduces metabolic syndrome in high fat-fed C57BL/6J mice. Here, we examined for the first time the effect of treatment with 77 mg/g GTE, Ex, or both (GTE + Ex) on genes related to the conversion of white adipose tissue (WAT) to brown fat-like adipose tissue (BLAT) in this model. GTE+Ex induced genes related to lipolysis (hormone sensitive lipase [3.0-fold] and patatin-like phospholipase domain-containing protein 2 [2-fold]), mitochondrial ß-oxidation (NADH dehydrogenase 5 [2.3-fold], cytochrome B [2.0-fold], and cytochrome C oxidase III [1.9-fold increase]), and adipose tissue browning (peroxisome proliferator-activated receptor-γ coactivator-1α [1.8-fold], bone morphogenetic protein 4 [2.6-fold], and phosphatase and tensin homolog [2.6-fold]) in visceral WAT compared to HF-fed mice. These results suggest that GTE+Ex function in part by inducing the conversion of WAT to BLAT and provides novel mechanistic insight into this combination.

Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.

Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17ß-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer.

Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells.

OBJECTIVE: Patatin-like phospholipase domain containing 3 (PNPLA3, adiponutrin) has been identified as a modifier of lipid metabolism. To better understand the physiological role of PNPLA3/adiponutrin, we have investigated its regulation in intact mice and human hepatocytes under various nutritional/metabolic conditions. MATERIAL/METHODS: PNPLA3 gene expression was determined by real-time PCR in liver of C57BL/6 mice after dietary treatments and in HepG2 cells exposed to various nutritional/metabolic stimuli. Intracellular lipid content was determined in HepG2 cells after siRNA-mediated knockdown of PNPLA3. RESULTS: In vivo, mice fed a high-carbohydrate (HC) liquid diet had elevated hepatic lipid content, and PNPLA3 mRNA and protein expression, compared to chow-fed mice. Elevated expression was completely abrogated by addition of unsaturated lipid emulsion to the HC diet. By contrast, in mice with high-fat diet-induced steatosis, Pnpla3 expression did not differ compared to low-fat fed mice. In HepG2 cells, Pnpla3 expression was reversibly suppressed by glucose depletion and increased by glucose refeeding, but unchanged by addition of insulin and glucagon. Several unsaturated fatty acids each significantly decreased Pnpla3 mRNA, similar to lipid emulsion in vivo. However, Pnpla3 knockdown in HepG2 cells did not alter total lipid content in high glucose- or oleic acid-treated cells. CONCLUSIONS: Our results provide evidence that PNPLA3 expression is an early signal/signature of carbohydrate-induced lipogenesis, but its expression is not associated with steatosis per se. Under lipogenic conditions due to high-carbohydrate feeding, certain unsaturated fatty acids can effectively suppress both lipogenesis and PNPLA3 expression, both in vivo and in a hepatocyte cell line.

Voluntary exercise and green tea enhance the expression of genes related to energy utilization and attenuate metabolic syndrome in high fat fed mice.

Obesity and metabolic syndrome are growing public health problems. We investigated the effects of decaffeinated green tea extract (GTE) and voluntary running exercise (Ex) alone or in combination against obesity and metabolic syndrome in high fat (HF) fed C57BL/6J mice. After 16 wk, GTE + Ex treatment reduced final body mass (27.1% decrease) and total visceral fat mass (36.6% decrease) compared to HF-fed mice. GTE + Ex reduced fasting blood glucose (17% decrease), plasma insulin (65% decrease), and insulin resistance (65% decrease) compared to HF-fed mice. GTE or Ex alone had less significant effects. In the skeletal muscle, the combination of Ex and GTE increased the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (Ppargc1a), mitochondrial NADH dehydrogenase 5 (mt-Nd5), mitochondrial cytochrome b (mt-Cytb), and mitochondrial cytochrome c oxidase III (mt-Co3). An increase in hepatic expression of peroxisome proliferator-activated receptor-α (Ppara) and liver carnitine palmitoyl transferase-1α (Cpt1a) and a decrease in hepatic expression of stearoyl-CoA desaturase 1 (Scd1) mRNA was observed in GTE + Ex mice. GTE + Ex was more effective than either treatment alone in reducing diet-induced obesity. These effects are due in part to modulation of genes related to energy metabolism and de novo lipogenesis.

(-)-Epigallocatechin-3-gallate inhibits pancreatic lipase and reduces body weight gain in high fat-fed obese mice.

Tea (Camellia sinensis, Theaceae) has been shown to have obesity preventive effects in laboratory studies. We hypothesized that dietary epigallocatechin-3-gallate (EGCG) could reverse metabolic syndrome in high fat-fed obese C57bl/6J mice, and that these effects were related to inhibition of pancreatic lipase (PL). Following treatment with 0.32% EGCG for 6 weeks, a 44% decrease in body weight (BW) gain in high fat-fed, obese mice (P < 0.01) was observed compared to controls. EGCG treatment increased fecal lipid content by 29.4% (P < 0.05) compared to high fat-fed control, whereas in vitro, EGCG dose-dependently inhibited PL (IC(50) = 7.5 µmol/l) in a noncompetitive manner with respect to substrate concentration. (-)-Epicatechin-3-gallate exhibited similar inhibitory activity, whereas the nonester-containing (-)-epigallocatechin did not. In conclusion, EGCG supplementation reduced final BW and BW gain in obese mice, and some of these effects may be due to inhibition of PL by EGCG.

(-)-Epigallocatechin-3-gallate increases the expression of genes related to fat oxidation in the skeletal muscle of high fat-fed mice.

(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to prevent the development of obesity in rodent models. Here, we examined the effect of EGCG on markers of fat oxidation in high fat-fed C57bl/6J mice. High fat-fed mice treated with 0.32% dietary EGCG for 16 weeks had reduced body weight gain and final body weight (19.2% and 9.4%, respectively) compared to high fat-fed controls. EGCG-treatment decreased fasting blood glucose, plasma insulin, and insulin resistance by 18.5%, 25.3%, and 33.9%, respectively. EGCG treatment also reduced markers of obesity-related fatty liver disease in high fat-fed mice. Gene expression analysis of skeletal muscle showed that EGCG increased mRNA levels of nuclear respiratory factor (nrf)1, medium chain acyl coA decarboxylase (mcad), uncoupling protein (ucp)3, and peroxisome proliferator responsive element (ppar)α by 1.4-1.9-fold compared to high fat-fed controls. These genes are all related to mitochondrial fatty acid oxidation. In addition, EGCG increased fecal excretion of lipids in high fat-fed mice. In summary, it appears that EGCG modulates body weight gain in high fat-fed mice both by increasing the expression of genes related fat oxidation in the skeletal muscle and by modulating fat absorption from the diet.