Liraglutide Improves Water Maze Learning and Memory Performance While Reduces Hyperphosphorylation of Tau and Neurofilaments in APP/PS1/Tau Triple Transgenic Mice.

The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 µg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes. The Morris water maze (MWM) was used to assess the spatial learning and memory. Liraglutide decreased levels of hyperphosphorylated tau and NFs in 3 × Tg liraglutide-treated (Tg + LIR) mice, increased ERK phosphorylation, and decreased JNK phosphorylation. Liraglutide also decreased the number of degenerative neurons in the hippocampus and cortex of Tg + LIR mice, and shortened their escape latencies and increased their hidden platform crossings in the MWM task. Liraglutide did not significantly affect the animals' body weight (BW) or fasting blood glucose. Liraglutide can reduce hyperphosphorylation of tau and NFs and reduce neuronal degeneration, apparently through alterations in JNK and ERK signaling, which may be related to its positive effects on AD-like learning and memory impairment.

Genistein induces G2/M arrest in gastric cancer cells by increasing the tumor suppressor PTEN expression.

Genistein, a major isoflavone found in soybeans, exhibits anticarcinogenic properties. The inhibitory effect of genistein on cell proliferation is associated with G2/M cell cycle arrest and inhibition of cdc2 activities. Here we assessed the role of PTEN in regulation of genistein-mediated G2/M cell cycle arrest in the gastric cancer cell lines (SGC-7901 and BGC-823). After 24 h following treatment, genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by genistein in SGC-7901 and BGC-823 cells is associated with increased phospho-cdc2 (Tyr15) and decreased cdc2 protein. Genistein treatment increased Wee1 levels and decreased phospho-Wee1 (Ser 642). Moreover, genistein substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in genistein-treated cells increased phospho-Wee1 (Ser642), whereas decreased phospho-Cdc2 (Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by genistein involved upregulation of PTEN.

[Effects of different diet composition on the expression of UCP2 mRNA in different tissues of rat].

OBJECTIVE: In order to explore effect of different diet composition on uncoupling proteins 2 (UCP2)-gene expression in rat brown adipose tissue, white adipose tissue and skeletal muscle. METHODS: Male Wistar rats were fed with different diets (including basic diet, high protein, high fat, high calorie 1 and 2 diet) for 2 months. The effects of the different diets on weight, the ratio of fat to body weight and free fatty acids were observed. Reverse transcription-polymerase chain reaction (RT-PCR) technique was used to measure the expression of UCP2 mRNA in rat brown adipose tissue, white adipose tissue and skeletal muscle. RESULTS: Body weight, the ratio of rat to body weight and free fatty acids in high calorie 1 and 2 diet groups are obviously higher than that in groups of basic diet, high protein, high fat diet (P < 0.05), but there is no significant difference between the last three groups (P > 0.05). UCP2 gene expression in white adipose tissue increases in high calorie diet 1 group and high calorie diet 2 group, and no significant difference in basic diet, high protein and high fat group with equal energy is observed. The expression of UCP2 mRNA between brown adipose tissue and muscle is similar in all groups. CONCLUSION: Energy can induce UCP2 mRNA expression in rat white adipose tissue, and expression level is related to store energy in body, but the expression of UCP2 mRNA in brown adipose tissue and muscle is unrelated to diet composition.

[Expression of uncoupling protein-2 mRNA in diet-induced obesity-resistant rats].

OBJECTIVE: To explore the expression of uncoupling protein-2 mRNA in brown adipose tissue, white adipose tissue and skeletal muscle of diet-induced obesity-resistant (DIO-R) rats. METHODS: Fifty male Sprague-Dawley (SD) rats were randomly divided into a control group and a high-fat group and fed with basic diet and high-fat diet respectively for 13 weeks. DIO-R and DIO rats were selected according to their body weight. The change of body weight and the intake of total calorie were observed. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of UCP2 mRNA in rat. RESULTS: Body weight and total calorie intake in DIO-R rats (425.1 +/- 27.1) g, (31,693 +/- 946) kJ were significantly lower than those in DIO rats (489.7 +/- 20.5) g, (34,363 +/- 1465) kJ. The peak area of UCP2 mRNA in white adipose tissue in DIO-R rats was 352 +/- 30 and in DIO rats was 101 +/- 12. The peak areas of UCP2 mRNA in skeletal muscle in DIO-R and DIO rats were 130 +/- 15 and 170 +/- 12, respectively. The peak areas of UCP2 mRNA in brown adipose tissue of DIO and DIO-R rats were 124 +/- 14 and 147 +/- 19, respectively. CONCLUSION: The expression of UCP2 mRNA in white adipose tissue of DIO-R rats increased significantly. These results suggest that obesity-resistance was associated with a tissue-specific increase in UCP2 expression.

[Effect of diet composition on expression of uncoupling protein-1 gene of rat].

In order to explore the effect of different diet composition on uncoupling proteins 1(UCP1) gene expression in brown adipose tissue, male Wistar rats are fed with different diets (basic diet, high protein diet, high fat diet, high calorie diet 1 and 2) for 2 months. The effects of different diets on weight and the ratio of fat mass to body weight are observed. Reverse transcription-polymerase chain reaction and western blotting technique are used to measure UCP1 mRNA and protein content of rat brown adipose tissue(BAT). The results show that body weight and the ratio of fat mass to body weight in high calorie 1 and 2 diet groups are obviously higher than those in groups of basic diet, high protein, and high fat diet (P < 0.05), but there is no significant difference among the last three groups (P > 0.05). UCP1 gene expression increases in both high calorie diet 1 group and 2 group, but it is not significantly different among basic diet, high protein and high fat diet groups with equal energy, indicating that energy can induce UCP1 gene expression of rat BAT.

[Effect of iron on the expression of uncoupling protein 2, 3 gene of obese rat].

In order to study the effect of iron on the expression of UCP2 in white fat and UCP3 in muscle in obese rats, a reverse transcription polymerase chain reaction (RT-PCR) technique is used to measure the expression of UCP2 and UCP3 mRNA. The results show: (1) Adequate iron improves the level of thyroid hormone in blood serum; (2) the body fat content of obese rat in 5, 10, and 20 times of iron supplement groups is lower than that of obese rats in normal iron supplement group; (3) the UCP2 and UCP3 mRNA expression of iron-deficient obese rats is low in iron-deficient obese rats; (4) iron supplement enhances the level of UCP3 mRNA expression in muscle and the level of UCP3 mRNA is the highest in the 5 times iron supplement group and about 2 times of that of basic diet group. However, there is no effect on the UCP2 mRNA expression induced by high energy diet. It suggested that adequate iron can improve the level of serum thyroid hormone, induce the UCP3 mRNA expression in muscle and mobilize fat to produce heat, but had no effect on UCP2 mRNA in white fat of obese rat.