Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8

The aging brain suffers mitochondrial dysfunction and a reduced availability of energy in the form of ATP, which in turn may cause or promote the decline in cognitive, sensory, and motor function observed with advancing age. There is a need for animal models that display some of the pathological features of human brain aging in order to study their prevention by e.g. dietary factors. We thus investigated the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) as a model for the age-dependent changes in mitochondrial function in the brain. To this end, 2-months old male SAMR1 (n = 10) and SAMP8 mice (n = 7) were fed a Western type diet (control groups) for 5 months and one group of SAMP8 mice (n = 6) was fed an identical diet fortified with 500 mg curcumin per kg. Dissociated brain cells and brain tissue homogenates were analyzed for malondialdehyde, heme oxygenase-1 mRNA, mitochondrial membrane potential (MMP), ATP concentrations, protein levels of mitochondrial marker proteins for mitochondrial membranes (TIMM, TOMM), the mitochondrial permeability transition pore (ANT1, VDAC1, TSPO), respiration complexes, and fission and fusion (Fis, Opa1, Mfn1, Drp1). Dissociated brain cells isolated from SAMP8 mice showed significantly reduced MMP and ATP levels, probably due to significantly diminished complex V protein expression, and increased expression of TSPO. Fission and fusion marker proteins indicate enhanced mitochondrial fission in brains of SAMP8 mice. Treatment of SAMP8 mice with curcumin improved MMP and ATP and restored mitochondrial fusion, probably by up-regulating nuclear factor PGC1α protein expression. In conclusion, SAMP8 compared to SAMR1 mice are a suitable model to study age-dependent changes in mitochondrial function and curcumin emerges as a promising nutraceutical for the prevention of neurodegenerative diseases that are accompanied or caused by mitochondrial dysfunction.     

艾燃烧生成物对SAM小鼠学习记忆行为的影响

目的：艾灸不仅可以延年益寿而且可以未病先防。然而仅有少量研究证实,艾灸的燃烧生成物具有抗氧化作用从而延缓衰老。本试验从行为学方面研究艾燃烧生成物对快速老化模型小鼠SAM—W8学习记忆行为的影响。方法：选用6月龄雄性快速老化模型（SAM）小鼠50只,其中SAM—R／1系10只作为空白组,SAM—W8系40只随机分为模型组、单纯艾烟熏吸组、无烟艾灸组和常规艾灸组,每组10只。选取关元穴为治疗穴位,令常规艾灸关元组小鼠在艾灸关元穴的同时处在一定浓度艾烟的环境中;单纯艾烟熏吸组小鼠处在与常规艾灸关元组相同浓度的艾烟环境但不艾灸其穴位;而无烟艾灸关元组则是在艾灸小鼠关元穴的同时立即将艾烟抽除;其余空白组和模型组小鼠进行相同的空白抓取。治疗前后分别进行学习记忆行为的被动逃避试验,并对实验结果进行分析。结果：与空白组比较,治疗前模型组及治疗各组小鼠进行被动逃避试验的潜伏期均明显变短,有显著性差异（P〈0．05,P〈0．05,P〈0．01,P〈0．01）,治疗后模型组及常规艾灸关元组小鼠治疗后潜伏期均明显缩短,有显著性差异（P〈0．01,P〈0．05）;与模型组比较,各治疗组小鼠治疗后潜伏期均明显延长,有显著差异（P〈0．01,P〈0．01,P〈0．05）。与治疗前比较,各治疗组治疗后潜伏期均较前明显延长,有显著性差异（P〈0．01,P〈0．05,P〈0．05）。结论：艾燃烧生成物可延长快速老化模型小鼠被动逃避试验的潜伏期。提示其在一定程度上改善老化模型小鼠的学习记忆功能,为今后艾灸抗衰老在临床上的应用开辟了新思路。     

Effects of Glycyrrhiza glabra polysaccharides on immune and antioxidant activities in high-fat mice

The purpose of this study was to investigate the immune and antioxidant activities of Glycyrrhiza glabra polysaccharides (GGP) in rats fed high-fat diet. The experiment was performed on four groups of growing Kunming mice. The results of the experiment showed a statistically significant decrease in serum antioxidant enzyme activities in high-fat group. Administration of GGP dose-dependently significantly enhanced immune and antioxidant enzyme activities in the GGP-treated mice compared to the high-fat model mice. It is concluded that GGP treatment can enhance immune activities, and reduce oxidative stress in high-fat mice.     

A Possible Link between Food and Mood: Dietary Impact on Gut Microbiota and Behavior in BALB/c Mice

Major depressive disorder is a debilitating disease in the Western World. A western diet high in saturated fat and refined sugar seems to play an important part in disease development. Therefore, this study is aimed at investigating whether saturated fat or sucrose predisposes mice to develop behavioral symptoms which can be interpreted as depression-like, and the possible influence of the gut microbiota (GM) in this. Fourty-two mice were randomly assigned to one of three experimental diets, a high-fat, a high-sucrose or a control diet for thirteen weeks. Mice on high-fat diet gained more weight (p = 0.00009), displayed significantly less burrowing behavior than the control mice (p = 0.034), and showed decreased memory in the Morris water maze test compared to mice on high-sucrose diet (p = 0.031). Mice on high-sucrose diet burrowed less goal-oriented, showed greater latency to first bout of immobility in the forced swim test when compared to control mice (p = 0.039) and high-fat fed mice (p = 0.013), and displayed less anxiety than mice on high-fat diet in the triple test (p = 0.009). Behavioral changes were accompanied by a significant change in GM composition of mice fed a high-fat diet, while no difference between diet groups was observed for sucrose preferences, LPS, cholesterol, HbA1c, BDNF and the cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12(p70), IL-17 and TNF-α. A series of correlations was found between GM, behavior, BDNF and inflammatory mediators. In conclusion, the study shows that dietary fat and sucrose affect behavior, sometimes in opposite directions, and suggests a possible association between GM and behavior.     

Hepatocyte-Specific Depletion of UBXD8 Induces Periportal Steatosis in Mice Fed a High-Fat Diet

We showed previously that UBXD8 plays a key role in proteasomal degradation of lipidated ApoB in hepatocarcinoma cell lines. In the present study, we aimed to investigate the functions of UBXD8 in liver in vivo. For this purpose, hepatocyte-specific UBXD8 knockout (UBXD8-LKO) mice were generated. They were fed with a normal or high-fat diet, and the phenotypes were compared with those of littermate control mice. Hepatocytes obtained from UBXD8-LKO and control mice were analyzed in culture. After 26 wk of a high-fat diet, UBXD8-LKO mice exhibited macrovesicular steatosis in the periportal area and microvesicular steatosis in the perivenular area, whereas control mice exhibited steatosis only in the perivenular area. Furthermore, UBXD8-LKO mice on a high-fat diet had significantly lower concentrations of serum triglyceride and VLDL than control mice. A Triton WR-1339 injection study revealed that VLDL secretion from hepatocytes was reduced in UBXD8-LKO mice. The decrease of ApoB secretion upon UBXD8 depletion was recapitulated in cultured primary hepatocytes. Accumulation of lipidated ApoB in lipid droplets was observed only in UBXD8-null hepatocytes. The results showed that depletion of UBXD8 in hepatocytes suppresses VLDL secretion, and could lead to periportal steatosis when mice are fed a high-fat diet. This is the first demonstration that an abnormality in the intracellular ApoB degradation mechanism can cause steatosis, and provides a useful model for periportal steatosis, which occurs in several human diseases.     

Energy balance and facultative diet-induced thermogenesis in mice fed a high-fat diet

The present study was aimed at studying energy balance in mice fed a high-fat diet. Albino mice were divided into three groups. One group had free access to the stock diet, whereas the two other groups consumed a high-fat diet. One of the high-fat fed groups was fed ad libitum, whereas the other was offered a restricted amount of the same diet so that its energy intake was comparable to the group of mice given the stock diet. Energy balance measurements, which included indirect calorimetry and carcass analysis, were performed. Brown adipose tissue (BAT) properties were also investigated. The results show that gains in both body weight and fat were higher in mice that had free access to high-fat diet than in mice fed the stock diet. In animals given a restricted amount of the high-fat diet, fat gain increased, whereas protein gain was reduced in comparison with animals fed the stock diet. Unrestricted access to the high-fat diet led to an increase in both energy intake and energy gain. As revealed by both slaughter and indirect calorimetry techniques energy expenditure was, in high-fat fed mice, 40% higher than in animals fed either stock or a restricted amount of high-fat diet. Nadolol was shown to suppress a large part of the elevated metabolic rate seen in mice fed an unrestricted high-fat diet. In those mice, BAT mitochondrial GDP binding was also increased. In summary, the present results confirm that adaptive diet-induced thermogenesis (DIT) develops in mice made hyperphagic by an energy-dense palatable diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Single-bulb garlic oil regulates toll-like receptors and Nrf2 cross-talk and IL-17 production in mice fed with high-fat diet

The present study aimed to evaluate the effect of single-bulb garlic oil (SGO) on toll-like receptors 3 and 4 (TLR3 and TLR 4) and nuclear erythroid factor-like 2 (Nrf2) signaling pathway resulted from a high-fat diet and its underlying mechanism. Twenty-four Balb/c mice allocated into six groups: 1) N: mice fed with standard chow; 2) HFD: mice fed a high-fat diet for 45 days without any treatment; 3) HFD + Simv: mice fed a high-fat diet for 45 days and treated with simvastatin; 4–6) HFD + SGO 100, 200, 400 (mice fed a high-fat diet for 45 days and treated with single-bulb garlic oil at dose: 100, 200, and 400 mg/kg body weight for 30 days), respectively. At the end of treatment, spleen and hepar were isolated. The flow cytometry analysis was performed to analyze the relative number of nrf2, superoxide dismutase (SOD), malondialdehyde (MDA), TLR3, TLR4 and interleukin (IL-17). The results showed that HFD induction significantly reduced Nrf-2 and antioxidant enzyme levels. Furthermore, HFD induction increased TLR3 and TLR4 signaling and IL-17 production. Interestingly, 200 mg/kg BW of SGO increased the relative number Nrf-2 followed by SOD and HO-1 elevation at a dose of 100 mg/kg BW. SGO100 notably decrease the relative number of TLR3 (CD11b⁺TLR3⁺) and TLR4 (CD11b⁺TLR4⁺). The production of IL-17 by CD4 and CD8 were also reduced after receiving SGO at 200 mg/kg BW. This study suggests that the protective effect of SGO treatment on HFD mice was achieved by modulating TLR-Nrf2 cross-talks and decreasing IL-17 production. Our findings support a potential beneficial role of SGO for treating metabolic disease caused by a high-fat diet.     

Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders

Free radical-mediated damage to neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD) and aging. The senescence accelerated prone mouse strain 8 (SAMP8) exhibits age-related deterioration in memory and learning along with increased oxidative markers. Therefore, SAMP8 is a suitable model to study brain aging and, since aging is the major risk factor for AD and SAMP8 exhibits many of the biochemical findings of AD, perhaps as a model for and the early phase of AD. Our previous studies reported higher oxidative stress markers in brains of 12-month-old SAMP8 mice when compared to that of 4-month-old SAMP8 mice. Further, we have previously shown that injecting the mice with alpha-lipoic acid (LA) reversed brain lipid peroxidation, protein oxidation, as well as the learning and memory impairments in SAMP8 mice. Recently, we reported the use of proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. In order to understand how LA reverses the learning and memory deficits of aged SAMP8 mice, in the current study, we used proteomics to compare the expression levels and specific carbonyl levels of proteins in brains from 12-month-old SAMP8 mice treated or not treated with LA. We found that the expressions of the three brain proteins (neurofilament triplet L protein, alpha-enolase, and ubiquitous mitochondrial creatine kinase) were increased significantly and that the specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and alpha-enolase) were significantly decreased in the aged SAMP8 mice treated with LA. These findings suggest that the improved learning and memory observed in LA-injected SAMP8 mice may be related to the restoration of the normal condition of specific proteins in aged SAMP8 mouse brain. Moreover, our current study implicates neurofilament triplet L protein, alpha-enolase, ubiquitous mitochondrial creatine kinase, lactate dehydrogenase B, and dihydropyrimidinase-like protein 2 in process associated with learning and memory of SAMP8 mice.     

Dietary-induced hypertrophic--hyperplastic obesity in mice

Metabolically intact NMRI mice and genetically obese NZO mice were fed ad lib. either a high-carbohydrate diet (standard) or a high-fat diet for a period of about 11 (NMRI mice) or 38 (NZO mice) wk. In both strains of mice, body weight increased more in the groups fed the high-fat diet. However, caloric intake by NMRI mice fed the high-fat diet was less than that of the controls. In NMRI mice fed the high-fat diet, epididymal and subcutaneous fat cell volumes increased; when these mice were fed the standard diet, only epididymal fat cell volume increased. Epididymal and subcutaneous fat cell numbers increased only in the group fed the high-fat diet. In NMRI mice fed either diet, the postprandial blood glucose was lower in older animals, but plasma insulin remained unchanged. The glucose tolerance deteriorated insignificantly. In NZO mice fed either diet, epididymal fat cell volumes and fat cell numbers increased. In this strain of mice the postprandial blood glucose and plasma insulin exhibited the strain-specific pattern, independent of the diet. In older animals fed either diet the glucose tolerance decreased.     

高脂饮食联合光照周期改变对不同性别小鼠体重的影响

摘要 目的：随着夜间光照与肥胖现象日趋普遍化,机体内的昼夜节律与生理代谢均受到不同程度的影响,其中不同性别间的差异有待进一步研究。本文旨在通过比较高脂饲料喂养,以及改变光照周期从而对不同性别小鼠体重产生的影响来模拟高脂肪饮食时人类受到夜间光照的性别差异。方法：随机选取C57BL/6小鼠雌鼠、雄鼠各12只,分别按照性别、喂养饲料随机均分成4组,其中随机选取一组雌鼠和一组雄鼠喂养60%高脂饲料作为实验组,另外的一组雌鼠和一组雄鼠喂养普通饲料作为对照组,连续喂养8周,观察并记录各组小鼠体重变化;第1~6周将实验小鼠置于24h/0h光照周期下生活,第6~8周实验小鼠生活的光照周期改为12h/12h。结果：在高脂饲料喂养以及光照周期失调（24h/0h）的条件下,雌、雄鼠体重均有增长（P<0.05）,但雄鼠体重增加量是雌鼠的三倍。当光照周期恢复正常（12h/12h）后,雌、雄小鼠体重增长量均下降。不同性别的小鼠食用高脂饲料以及生物节律被打乱时体重均增加,但雄鼠体重增加量明显大于雌鼠,提示同在高脂饲料饮食的条件下,雌鼠受生物节律影响比雄鼠更大。结论：高脂饮食实验小鼠模型中雌鼠受生物节律的影响比雄鼠更大。     

Acupuncture accelerates neural regeneration and synaptophysin production after neural stem cells transplantation in mice

BACKGROUNDSynaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease (AD) patients. Exogenous neural stem cells (NSCs) improve the damaged nerve function. The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment.AIMTo explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment.METHODSNSCs were isolated from pregnant senescence-accelerated mouse resistant 1 (SAMR1) mice, labeled with BrdU, and injected into the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old senescence-accelerated mice (SAM) were randomly divided into six groups: SAMR1 (RC), SAMP8 (PC), sham transplantation (PS), NSC transplantation (PT), NSC transplantation with acupuncture (PTA), and NSC transplantation with non-acupoint acupuncture (PTN). Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation. Hematoxylin-eosin staining and immunofluorescence were used to observe the his-topathological changes and NSC proliferation in mice. A co-culture model of hippocampal slices and NSCs was established in vitro, and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment.RESULTSMorris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8, which improved in all the NSC transplantation groups. The behavioral change in the PTA group was stronger than those in the other two groups (P < 0.05). Histopathologically, the hippocampal structure was clear, the cell arrangement was dense and orderly, and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group. The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups, and the number increased significantly in the PTA group than in the PT and PTN groups (P < 0.05). Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro, the synaptophysin expression in the PC group decreased in comparison to the RC group, that in PT, PTA, and PTN groups increased as compared to the PC group, and that in the PTA group increased significantly as compared to the PTN group with acupoint-related specificity (P < 0.05).CONCLUSIONAcupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.     

Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway

Metabolic stress induced by high-fat (HF) diet leads to cognitive dysfunction and aging, but the physiological mechanisms are not fully understood. Senescence-accelerated prone mouse (SAMP8) models were conducted under metabolic stress conditions by feeding HF for 15 weeks, and the preventive effect of resveratrol was studied. This dietary strategy demonstrates cognitive impairment in SAMP8-HF and significant preventive effect by resveratrol-treated animals. Hippocampal changes in the proteins involved in mitochondrial dynamics optic atrophy-1 protein (OPA1) and mitofusin 2 (MFN2) comprised a differential feature found in SAMP8-HF that was prevented by resveratrol. Electronic microscopy showed a larger mitochondria in SAMP8-HF + resveratrol (SAMP8-HF + RV) than in SAMP8-HF, indicating increases in fusion processes in resveratrol-treated mice. According to the mitochondrial morphology, significant increases in the I-NDUFB8, II-SDNB, III-UQCRC2, and V-ATPase complexes, in addition to that of voltage-dependent anion channel 1 (VDAC1)/porin, were found in resveratrol-treated animals with regard to SAMP8-HF, reaching control-animal levels. Moreover, tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) were increased after HF, and resveratrol prevents its increase. Moreover, we found that the HF diet affected the Wnt pathway, as demonstrated by β-catenin inactivation and modification in the expression of several components of this pathway. Resveratrol induced strong activation of β-catenin. The metabolic stress rendered in the cognitive and cellular pathways altered in SAMP8 focus on different targets in order to act on preventing cognitive impairment in neurodegeneration, and resveratrol can offer therapeutic possibilities for preventive strategies in aging or neurodegenerative conditions.     

Dietary fat modulation of apoA-II metabolism and prevention of senile amyloidosis in the senescence- accelerated mouse

Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, safflower oil, or fish oil were fed to male mice for 26 weeks. The serum HDL cholesterol was significantly lower (P < 0.01) in mice on the diet containing fish oil (7.4 +/- 3.0 mg/dl) than in mice on the butter diet (38.7 +/- 12.5 mg/dl), which in turn had significantly lower (P < 0.01) HDL levels than mice on the safflower oil diet (51.9 +/- 5.6 mg/dl). ApoA-II was also significantly lower (P < 0.01) in mice on the fish oil diet (7.6 +/- 2.7 mg/dl) than on the butter (26.9 +/- 7.3 mg/dl) or safflower oil (21.6 +/- 3.7 mg/dl) diets. The mice fed fish oil had a significantly greater ratio (P < 0.01) of apoA-I to apoA-II, and a smaller HDL particle size than those fed butter and safflower oil. Severe AApoAII deposits in the spleen, heart, skin, liver, and stomach were shown in the fish oil group compared with those in the butter and safflower oil groups (fish oil > butter > safflower oil group, P < 0.05). These findings suggest that dietary fats differ in their effects on serum lipoprotein metabolism, and that dietary lipids may modulate amyloid deposition in SAMP1 mice.     

Role of insulin signaling impairment,adiponectin and dyslipidemia in peripheral and central neuropathy in mice

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype.KEY WORDS: Glucose, High-fat diet, Insulin, Neuropathy     

葛仙米多糖对高脂小鼠血脂和肠道微生物的影响

[目的]研究葛仙米多糖对高脂饲料喂养小鼠血脂和肠道微生物的影响.[方法]将健康的8周龄雄性小鼠分成5组,每组10只:正常组C57/6CNC小鼠(N:灌胃生理盐水,喂饲标准饲料),对照组ApoE-/-小鼠(C:灌胃生理盐水,喂饲标准饲料),模型组ApoE-/-小鼠(M:灌胃生理盐水,喂饲高脂高胆固醇饲料),葛仙米多糖低剂...     

Effect of Low-Selenium/High-Fat Diet on Pig Peripheral Blood Lymphocytes: Perspectives from Selenoproteins,Heat Shock Proteins,and Cytokines

The aim of the present study was to clarify the effect of low selenium (Se)/high fat on the mRNA expression of selenoproteins, heat shock proteins (HSPs) and cytokines in pig peripheral blood lymphocytes. Forty crossbred boar piglets with healthy lean body weights of 10 kg were randomly divided into four treatment groups (group C, group L-Se, group H-fat, and group L-Se-H-fat) (n = 10/group) and fed with the corresponding diet for 16 weeks. The pig peripheral blood lymphocytes were extracted, and the mRNA expression of selenoproteins, HSPs, and cytokines was measured. Most mRNA levels for selenoproteins decreased in group L-Se, group H-fat, and group L-Se-H-fat, except Gpx1, Gpx2, Selt, and Selm, which were elevated in group H-fat. At the same time, low-Se/high-fat diet increased the expression of HSPs (HSP40, HSP60, HSP70, and HSP90) and inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, IL-9, iNOS, COX-2, NF-κB, and TNF-α) in group L-Se, group H-fat, and group L-Se-H-fat, and genes in group L-Se-H-fat showed greater increases. Also, low-Se/high-fat diet inhibits the expression of TGF-β1 and IFN-γ. In summary, a low-Se/high-fat diet can cause relevant selenoprotein expression changes and promote the expression of pro-inflammatory factors and HSPs, and low Se enhances the expression of HSPs and inflammation factors induced by high fat. This information is helpful for understanding the effects of low-Se and high-fat diet on pig peripheral blood lymphocytes.     

Protective effect of xanthohumol against age-related brain damage

It has been recently shown that xanthohumol, a flavonoid present in hops, possesses antioxidant, anti-inflammatory and chemopreventive properties. However, its role in the aging brain has not been addressed so far. Therefore, this study aimed to investigate the possible neuroprotective activity of xanthohumol against age-related inflammatory and apoptotic brain damage in male senescence-accelerated prone mice (SAMP8). Animals were divided into 4 groups: Untreated young mice, untreated old mice and old mice treated either with 1 mg kg⁻¹ day⁻¹ or 5 mg kg⁻¹ day⁻¹ xanthohumol. Young and old senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and their brains were collected and immediately frozen in liquid nitrogen. mRNA (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, XIAP, NAIP and Bcl-2) and protein (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, BDNF, synaptophysin and synapsin) expressions were measured by RT-PCR and Western blotting, respectively. Significant increased levels of pro-inflammatory (TNF-α, IL-1β) and pro-apoptotic (AIF, BAD, BAX) markers were observed in both SAMP8 and SAMR1 old mice compared to young animals (P<.05) and also in SAMP8 untreated old mice compared to SAMR1 (P<.05). These alterations were significantly less evident in animals treated with both doses of xanthohumol (P<.05). Also, a reduced expression of synaptic markers was observed in old mice compared to young ones (P<.05) but it significantly recovered with 5 mg kg⁻¹ day⁻¹ xanthohumol treatment (P<.05). In conclusion, xanthohumol treatment modulated the inflammation and apoptosis of aged brains, exerting a protective effect on damage induced by aging.     

Effects of orexin-A on memory processing

Orexin-A is an endogenous peptide with receptors present throughout the brain. Here, we examined the effect of post-training administration of orexin-A on retention in active and passive avoidance. Orexin-A administered by intracerebroventricular (i.c.v.) injection to CD-1 mice post-training improved retention in both T-maze footshock avoidance and one trial step-down passive avoidance. SAMP8 mice have age-related deficits in learning and memory, which correlate with an increase in brain levels of beta amyloid (Abeta) and an impaired response to memory-enhancing compounds. Orexin-A at 3nmol improved retention in young and old SAMP8 mice. These findings show that orexin-A can improve memory even with overproduction of Abeta.     

Anti-obesity property of the brown seaweed,Sargassum polycystum using an in vivo animal model

Obesity has reached epidemic proportions in many countries around the world. Preventing and treating obesity is becoming an increasing priority due to dissatisfaction with high costs and hazardous side effects of anti-obesity drugs. This study was designed to investigate the anti-obesity properties of the Sabah brown seaweed, Sargassum polycystum, on body weight and blood plasma levels of rats fed a high-fat diet supplemented with different doses of the seaweed powder. Male Sprague Dawley rats were divided into five groups, representing control negative (CN) group, control positive (CP) group, low dosage group (LDG), medium dosage group (MDG) and high dosage group (HDG). The study duration was 8 weeks. All groups were fed high-fat diet throughout the study except for CN group, which was fed normal rat chow. LDG, MDG and HDG were supplemented high-fat diet with 2.5, 5.0 and 10.0 % seaweed powder, respectively. By comparing with the CP group, it was found that the HDG (10.0 % seaweed treatment diet) showed the greatest effect in suppressing weight gain, followed by the MDG (5.0 % seaweed treatment diet) and LDG (2.5 % seaweed treatment diet). The HDG decreased the levels of plasma total cholesterol and triglycerides. This finding shows that S. polycystum powder treatment had a positive effect on the inhibition of weight gain and has a promising value in preventing obesity.     

Time-restricted feeding prevents high-fat and high-cholesterol diet-induced obesity but fails to ameliorate atherosclerosis in apolipoprotein E-knockout mice

One of the leading risk factors for atherosclerosis is obesity, which is commonly caused by a nutrient-rich Western-style diet, sedentary behaviors, and shift work. Time-restricted (TR) feeding and intermittent fasting are both known to prevent overweight and adiposity, improve glucose tolerance, and decrease plasma cholesterol in high-fat diet-induced obese mice. Here we examined the overall effects of TR feeding of a Western diet (fat, 40.5 Kcal%; cholesterol, 0.21 g%) using 8-week-old Apoe^−/− mice. Mice were assigned into three groups: (1) an ad libitum (AL) group fed an AL Western diet, (2) a TR group with restricted access to a Western diet (15 h/day, 12:00 to 3:00 Zeitgeber time [ZT]); and (3) an Ex/TR group fed a TR Western diet and subjected to physical exercise at 12:00 ZT. Mice in the AL group gained body weight rapidly during the 14-week observation period. With TR feeding, excessive weight gain, liver adiposity, visceral fat, and brown adipose tissue volume were effectively suppressed. Although TR feeding failed to decrease Oil Red O-stained aortic plaques in Apoe^−/− mice, physical exercise significantly decreased them. Neither TR feeding with exercise nor that without exercise decreased the mean area under the curve of the plasma cholesterol level or the fasting plasma glucose. Collectively, TR feeding of a Western diet prevented the development of obesity but failed to ameliorate atherosclerosis in Apoe^−/− mice.