Xue Tang

Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity

Recent studies have investigated the anti-obesity effect of resveratrol, but the pathways through which resveratrol resists obesity are not clear. In the present study, we hypothesize that resveratrol exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes, and in turn, improving fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high-fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several biochemical markers are measured. Fluorescence in situ hybridization and flow cytometry are used to monitor and quantify the changes in gut microbiota. The key genes related to fat storage and metabolism in the liver and visceral adipose tissues are measured by real-time PCR. The results show that resveratrol (200 mg per kg per day) significantly lowers both body and visceral adipose weights, and reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut microbiota dysbiosis induced by the HF diet, including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Enterococcus faecalis, and increasing the growth of Lactobacillus and Bifidobacterium. Furthermore, resveratrol significantly increases the fasting-induced adipose factor (Fiaf, a key gene negatively regulated by intestinal microbes) expression in the intestine. Resveratrol significantly decreases mRNA expression of Lpl, Scd1, Ppar-γ, Acc1, and Fas related to fatty acids synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf expression. The Pearsons correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and in turn, through the Fiaf signaling pathway, accelerates the development of obesity.

Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress.

High fat diets induce oxidative stress which may be involved in neurodegenerative diseases. Quercetin is a kind of antioxidant that has neuroprotective effects and potent7ial pro-oxidant effects as well. In this study, we evaluated cognitive function in mice fed with high fat diets and basic diets with or without quercetin. Male Chinese Kunming (KM) mice were randomly assigned to five groups fed with basic diet (Control), basic diet with 0.005% (w/w) quercetin (CQ1), high fat diet (HFD), HFD with 0.005% (w/w) quercetin (HFDQ1) and 0.01% (w/w) quercetin (HFDQ2) for 13weeks. At the end of the study period, fasting blood glucose (FBG), plasma and hippocampal markers of oxidative stress, plasma lipid status, Morris water maze as well as hippocampal relative mRNA expression of akt, bdnf, camkII, creb, gsk-3β, nrf2 and pi3k were examined. The results suggested that in comparison to the control group, the escape latency was increased and percent time spent in the target quadrant was decreased, with increased reactive carbonyls, malondialdehyde (MDA) and declined expression of pi3k, akt, nrf2, creb and bdnf in the hippocampus of HFD and CQ1 groups. Conversely, higher quercetin supplemented to HFD improved antioxidant capacity and reversed cognitive decline completely. Significant correlations between the redox status and cognition-related gene expression were observed as well (P<0.05). Thus, in the case of oxidative stress, an appropriate dose of quercetin can attenuate oxidative stress to improve hippocampus dependent cognition. But under a balanced situation, quercetin exerts pro-oxidant effects to impair cognition.

Role of thyroid hormone homeostasis in obesity-prone and obesity-resistant mice fed a high-fat diet

BACKGROUND The exact mechanism for different propensities to obesity when consuming a high-fat diet (HFD) is largely unknown. Thyroid hormone (TH) is an important modulator of energy homeostasis and body weight. OBJECTIVE The present study aimed to find the potential mechanisms of TH in the development of obesity-prone (OP) and obesity-resistant (OR) mice after short-term and long-term HFD feeding. METHODS C57Bl/6 male mice were randomly divided into two groups: a low-fat diet (LFD) group and an HFD group. In the 7th week, HFD-fed mice were classified as OP or OR according to upper and lower tertiles of body weight. Half of the mice were sacrificed at this time point and the remaining mice were kept on feeding and sacrificed in the 27th week. Indirect calorimetry was performed. At harvest, serum was used for ELISA assays and oxidative stress biomarkers determination. Tissues were dissected for deiodinases activity and relative mRNA expression determination, as well as antioxidant capacity evaluation. RESULTS In the 7th week, OP mice showed a significant body weight gain, decreased energy expenditure (EE), normal circulating TH levels, and activated HPT axis, whereas OR mice had normal body weight and maintained T(3) levels only through enhancing hepatic D1 activity. In the 27th week, OR mice gained more body weight than LFD mice accompanied by an activation of HPT axis and decreased hepatic deiodination. Genes involved in TH production were down-regulated in OP mice and up-regulated in OR mice. Changes in deiodinases activity and thyroid function were related with redox status in specific tissues. Furthermore, OP mice had more serious hepatic steatosis than OR mice, with up-regulation of T(3) target genes (e.g. Srebp1c, Acc1, Fasn) involved in lipid synthesis and down-regulation of Pgc1α, Cyp7a1 and Cpt1α. CONCLUSIONS HPT axis function and deiodinases activity might be involved in different propensities to obesity and the ability of OR mice to resist obesity was limited.

Effects of heat treatment on structural modification and in vivo antioxidant capacity of soy protein.

OBJECTIVE The present study identified the effects of heat oxidation on protein carbonyl content and α,α-diphenyl-β-picrylhydrazyl (DPPH) free radical-scavenging activity in soy protein. The changes on antioxidant status in male mice fed a heat-oxidized diet were also investigated. METHODS Soy protein heated at 100°C for 30, 60, and 90 min was used to determine the protein carbonyl content and DPPH free radical-scavenging activity in vitro. Male KM mice (3 wk old) were fed a normal diet, an oxidized diet (HD) containing 12% heat-oxidized soy protein, or an HD supplemented with 0.1% lipoic acid. After 4 wk of feeding, apparent digestibility, reactive oxygen species, malondialdehyde, and total antioxidant capacity levels were measured. The antioxidant enzyme activities in serum and tissues were also assayed. RESULTS Heat-oxidized soy protein showed a significant increase in protein carbonyl formation and a decrease in DPPH free radical-scavenging activity. The HD induced a significant decrease in food intake and apparent digestibility of dry matter and crude protein in mice. Increased levels of reactive oxygen species and malondialdehyde in serum and tissues accompanied by decreased total antioxidant capacity and antioxidant enzyme activities were also observed in HD-fed mice. These changes were partly restored in the lipoic acid-treated group. CONCLUSION Heat-oxidized soy protein showed a relatively higher protein carbonyl content and a loss of its free radical-scavenging activity in vitro. The heat oxidation also led the soy protein to generate reactive oxygen species, decrease the antioxidant status, and induce redox imbalance in vivo. The heat oxidation of food protein could be a potential health risk in humans.

Structural and antioxidant modification of wheat peptides modified by the heat and lipid peroxidation product malondialdehyde.

Wheat peptides, the biological active peptides derived from foods, has an array of biological actions, including antiobesity, antimicrobial, and angiotensin I-converting enzyme inhibitory effects in mammalian species. Recent studies showed that some wheat peptides may show the noteworthy antioxidant potency against the peroxidation of lipids or fatty acids, but the effect of oxidation on its antioxidant activities is unclear. In the present study, we demonstrate that heat and malandialdehyde (MDA)-oxidized wheat peptides lose its surface hydrophobicity and reducing power, and show a relatively lower free radical-scavenging activitiy in vitro. Those modifications also lead to gradual formation of aggregates in wheat peptides and induce more reactive oxygen species (ROS) production in vivo. These findings indicate that oxidation may influence the functional properties and directly alter the structure of wheat peptides, and lead to the loss of its antioxidant potency both in vitro and in vivo, thereby providing a novel explanation for some of the potential health risks proposed for oxidized food in human.

Comparative in vivo antioxidant capacity of DL‐2‐hydroxy‐4‐methylthiobutanoic acid (HMTBA) and DL‐methionine in male mice fed a high‐fat diet

BACKGROUND In animal diets, methionine (Met) is considered to be the first limiting amino acid, and the activity of synthetic Met is typically added either as DL-methionine (DLM) or as DL-2-hydroxy-4-methylthiobutanoic acid (HMTBA). It has been demonstrated that HMTBA exhibits a higher antioxidant capability in vitro as compared to DLM. However, the difference in antioxidant capability between DLM and HMTBA in vivo is unknown. METHODS In the present study, 60 male C57BL/6 mice were randomly divided into six groups and fed either a normal diet (NFD, 5.37% fat) or a high-fat diet (HFD, 19.7% fat) in conjunction with 0.2% DLM, 0.2% HMTBA or 0.1% DLM and 0.1% HMTBA for 4 weeks. RESULTS HFD supplemented with 2% DLM and NFD with 2% HMTBA both induced adverse affects in relation to serum lipid parameters and depressed antioxidant defense systems in the digestive system. However, these changes were restored in the 0.2% HMTBA-treated HFD group. Furthermore, no significant differences were found in the lipid parameters and antioxidant status in the NFD and HFD group supplemented with 0.1% DLM and 0.1% HMTBA. CONCLUSION HMTBA restored oxidative redox status under OS conditions and its antioxidant properties were positively correlated with the dosage included in diet.

Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet

Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.

Differences in muscle cellularity and flesh quality between wild and farmed Coilia nasus (Engraulidae).

BACKGROUND Populations of Coilia nasus, an anadromous fish, have declined dramatically in the Yangtze River estuary and its associated lakes owing to excessive fishing and changes in aquatic ecology. Recently, the success of artificial breeding programmes and advanced methods of propagation have allowed great increases in production of this species. Thus, to gain a better understanding of the flesh quality of C. nasus, muscle cellularity and quality parameters of the flesh were studied in wild and farmed specimens. RESULTS Muscle cellularity was different between wild and farmed fish. Muscle fibre density was significantly higher in farmed specimens, while muscle fibre diameter was higher in wild specimens. Farmed fish had higher moisture, hydroxyproline and collagen contents and a lower fat content compared with wild fish. No significant differences in textural parameters were found between the two groups. Saturated (SFA), polyunsaturated (PUFA) and total n-6 fatty acid contents were significantly higher in farmed fish, but monounsaturated fatty acid (MUPA) content was higher in wild fish. CONCLUSION The variation in the studied parameters determined significant differences in the flesh quality of wild and farmed C. nasus. Depending on muscle cellularity and fatty acid composition, farmed fish could be more suitable for human consumption than wild fish.

Effects of dietary oxidized tyrosine products on insulin secretion via the thyroid hormone T3-regulated TRβ1–Akt–mTOR pathway in the pancreas

Oxidized tyrosine products (OTPs) have been detected in commercial foods with high protein content. Dityrosine (Dityr) is a typical oxidized tyrosine product. The previous studies in our lab demonstrated that dityrosine administration impaired glucose tolerance and suppressed the bio-function of thyroid hormone T3 of mice. The T3-activated Akt–mTOR signaling pathway plays important roles in insulin synthesis in pancreatic β cells. Due to the structural homology between dityrosine and T3, the molecular binding domain for these two compounds in TRβ1 might be the same site. Therefore, the present study investigates the potential impact of dietary OTPs on the pancreatic function. Sprague Dawley (SD) rats were fed a diet containing OTPs for 12 weeks. In addition, a 10 week gavage experiment using C57BL/J mice was performed to explore whether dityrosine was responsible for the injury induced by OTPs. The blood glucose, plasma insulin levels, and plasma free thyroid hormones (THs) were then measured. After 12 week dietary OTPs or 10 week OTPs/dityrosine gavage, elevated fasting blood glucose and decreased plasma insulin levels were detected both in rats and mice in the presence of enhanced plasma free THs content, which indicated dysfunction of the pancreatic islets and that the regulation of T3 to insulin synthesis was suppressed by OTPs and dityrosine. A cell experiment using mouse MIN-6 cells was performed to explore the mechanism of the diminished T3 bio-function in pancreatic islets induced by dityrosine. Dityrosine incubation attenuated the T3-mediated insulin synthesis via an indirect way of regulating the mRNA expression of genes related to insulin synthesis and decreasing the protein level of TRβ1. In addition, dityrosine inhibited the Akt phosphorylation activated by T3 in MIN-6 cells. Dityrosine treatment altered the T3-activated translation factors involved in the Akt–mTOR signaling pathway. These findings indicate that decreased insulin secretion triggered by dietary OTPs may be mediated by suggested T3-stimulated protein synthesis in pancreatic β cells.