Chia Seed Does Not Improve Cognitive Impairment in SAMP8 Mice Fed with High Fat Diet.

BACKGROUND: Chia seed is an ancient seed with the richest plant source of α-linolenic acid, which has been demonstrated to improve metabolic syndrome associated risk factors. Under high fat diet (HFD) condition, the senescence-accelerated mouse-prone 8 (SAMP8) mice demonstrated worsen Alzheimer's disease (AD) related pathology compared to low fat diet fed SAMP8 mice. OBJECTIVE: To explore whether chia seed supplementation might improve cognitive impairment under aging and metabolic stress via high fat diet (HFD) fed SAMP8 mice as a model. DESIGN: SAMP8 mice and senescence-accelerated mouse-resistant 1 (SAMR1) were randomized into 4 groups, i.e., SAMR1 low fat diet group (SAMR1-LFD), SAMP8-HFD and SAMP8-HFD group supplemented with 10% chia seed (SAMP8-HFD+Chia). At the end of the intervention, cognitive function was measured via Morris water maze (MWM) test. Hippocampus and parietal cortex were dissected for further analysis to measure key markers involved AD pathology including Aß, tau and neuro-inflammation. RESULTS: During navigation trials of MWM test, mice in SAMP8-LFD group demonstrated impaired learning ability compared to SAMR1-LFD group, and chia seed had no effect on learning and memory ability for HFD fed SAMP8 mice. As for Alzheimer's disease (AD) related pathology, chia seed not only increased α-secretase such as ADAM10 and insulin degrading enzyme (IDE), but also increased ß-secretase including beta-secretase 1 (BACE1) and cathepsin B, with an overall effects of elevation in the hippocampal Aß42 level; chia seed slightly reduced p-Tauser404 in the hippocampus; while an elevation in neuro-inflammation with the activation of glial fibrillary acidic protein (GFAP) and Ibα-1 were observed post chia seed supplementation. CONCLUSIONS: Chia seed supplementation did not improve cognitive impairment via MWM in HFD fed SAMP8 mice. This might be associated with that chia seed increased key enzymes involved both in non-amyloidogenic and amyloidogenic pathways, and neuro-inflammation. Future studies are necessary to confirm our present study.

Chia Seed Supplementation Reduces Senescence Markers in Epididymal Adipose Tissue of High-Fat Diet-Fed SAMP8 Mice.

Adipose tissue is a key organ with substantial senescent cell accumulation under both obesity and aging conditions. Chia seed is an ancient seed and is the richest plant source of α-linolenic acid. We aimed to determine how cellular senescence markers will be altered in adipose tissue of senescence-accelerated mouse-prone 8 (SAMP8) mice fed with high-fat diets (HFDs); and how chia seed can affect the above markers. SAMP8 mice and their control senescence-accelerated mouse-resistant 1 (SAMR1) were divided into four groups, that is, SAMR1 low-fat diet group (R1LF), SAMP8LF group (P8LF), SAMP8 high-fat group (P8HF), and SAMP8HF group supplemented with 10% chia seed (P8HC). At the end of the intervention, body composition was measured through T1-weighted magnetic resonance imaging, and epididymal (EPI) and subcutaneous (SC) adipose tissues were dissected for further analysis. Compared with the R1LF group, the P8HF and P8HC groups had significantly increased body fat mass. In EPI fat, p16, CD68 and PAI-1 mRNA expression from P8HF group were significantly increased; chia seed partially reduced p16 and CD68 mRNA expression. The P8LF group has increased p16 and CD68, and the P8HF group has increased p16, p21, and CD68; and P8HC group has increased p16 mRNA expression. The protein expression of p-AMPK in EPI and SC fat from the P8HF group was reduced. In conclusion, reductions in AMPK activity might be partially responsible for elevation in HFD-induced senescence markers in both EPI and SC fat, and chia seed supplementation is able to reduce senescence-associated markers at least in EPI adipose tissue.

Reproductive factors and risk of Parkinson's disease in women: A meta-analysis of observational studies.

Evidence on the relationship between reproductive factors, use of oral contraceptives (OCs) and the incidence of Parkinson's disease (PD) remain inconclusive. The aim of this meta-analysis is to evaluate whether relevant reproductive factors including age at menarche, age at menopause, fertile lifespan, parity, type of menopause (surgical versus natural), and use of OCs are associated with risk of PD in women via random-effects model. PubMed and EMBASE database were used to search for case-control or cohort studies published before February17, 2017. 6 case-control and 5 cohort studies were included in the meta-analysis. The pooled relative risks (RRs) of PD risk were 1.00 (95% CI: 0.79-1.28) for use of OCs (ever versus never), 1.03 (95% CI: 0.84-1.26) for age at menarche, 0.98 (95% CI: 0.75-1.29) for age at menopause, 0.98(95% CI: 0.77-1.25) for fertile lifespan, 0.99(95% CI:0.0.79-1.25) for parity, 0.93 (95% CI:0.68-1.29) for type of menopause (surgical versus natural). In the subgroup analysis stratified by study design, age, caffeine intake and smoking, an inverse association was found between surgical menopause and risk of PD for those adjusting for caffeine intake (RR: 0.67, 95% CI: 0.45-0.99) and smoking (RR: 0.77, 95% CI: 0.63-0.94); while a positive association was found between surgical menopause and PD risk for those not adjusting for smoking (RR: 1.91, 95% CI: 1.29-2.83). In conclusion, our meta-analysis provided little epidemiological support for the role of reproductive factors in the incidence of PD. Whether surgical menopause is inversely associated with the risk of PD requires further explorations.

Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-α secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes.

Background: Rosmarinic acid (RA) is a natural phenol carboxylic acid with many promising biological effects. It may be a suitable candidate for improving obesity-related adipose tissue dysfunction. Objective: We aimed to investigate the therapeutic use of RA as an anti-obesity agent by measuring its effects on adipogenesis, lipolysis, and messenger RNA (mRNA) expression of major adipokines in 3T3-L1 adipocytes; and its effects on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) secretion in macrophages and inflammatory mediators in 3T3-L1 adipocytes incubated with macrophage-conditioned medium (MCM). Methods: 3T3-L1 preadipocytes were used to explore how RA affects adipogenesis, as well as the involvement of phosphorylated extracellular signal-regulated kinase-1/2 (p-ERK1/2) and mothers against decapentaplegic homolog 3 (p-Smad3). 3T3-L1 preadipocytes were also differentiated into mature adipocytes to explore how RA affects basal and isoproterenol- and forskolin-stimulated lipolysis; and how RA affects key adipokines' mRNA expression. RAW 264.7 macrophages were stimulated with LPS in the absence or presence of RA to explore RA's effects on TNF-α secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA's effects on interleukin-6 (IL-6), IL-1ß, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression. Results: During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein-α, and activated p-ERK1/2 and p-Smad3; inhibition of adipogenesis by RA was partially restored following treatment with p-ERK1/2 and p-Smad3 inhibitors. In mature adipocytes, RA inhibited basal lipolysis; phosphodiesterase-3 inhibitor reversed this. RA also inhibited isoproterenol- and forskolin-stimulated glycerol and free fatty acid release, and the phosphorylation of hormone-sensitive lipase and perilipin. RA had no effects on leptin, adiponectin, resistin, or visfatin mRNA expression. RA suppressed TNF-α mRNA expression and secretion in LPS-stimulated RAW 264.7 macrophages; and reduced LPS-MCM-induced IL-6, IL-1ß, MCP-1, and RANTES mRNA expression in 3T3-L1 adipocytes. Conclusions: RA exerts inhibitory effects on adipogenesis, lipolysis, and inflammation. RA could be a promising natural product for improving adipose mobilization in obesity.

Effects of vitamin D and resveratrol on metabolic associated markers in liver and adipose tissue from SAMP8 mice.

SAMP8 mice exhibit multiple metabolic characteristics associated with age, and it is a suitable candidate for researching aging associated metabolic dysfunction. OBJECTIVES: We aimed to 1) explore how key metabolic markers will be altered in both liver and adipose tissue with aging in SAMP8 mice; and 2) how the combination of vitamin D (VD) with resveratrol (RSV) will affect aging associated metabolic impairment in liver and adipose tissue from SAMP8 mice. METHODS: SAMP8 mice and their control SAMR1 mice were divided into 5 groups, i.e. SAMR1, SAMP8, SAMP8 mice supplemented with VD, RSV and VD combined with RSV group, respectively. At the end of the intervention, glucose and insulin tolerance, p-AMP-activated protein kinase (AMPK) and amyloid precursor protein (APP), and endoplasmic reticulum (ER) stress markers in liver and adipose tissue, adiponectin secretion, p-NF-κBp65 and TNF-α protein expression in adipose tissue were determined. RESULTS: Compared to SAMR1 control, SAMP8 mice demonstrate impaired glucose tolerance and reduction in circulating adiponectin level; in the liver, SAMP8 mice have reduction in p-Aktser473, elevation in PTP1B and APP, p-eIF2α, GRP78 and p-JNK protein expression. In epididymal (EPI) fat, SAMP8 mice also have elevated p-Aktser473 and PTP1B compared to SAMR1 mice. In both epididymal (EPI) and subcutaneous (SC) fat, there were elevated ER stress markers, reduced p-AMPK and elevated APP, as well as elevated p-NF-κBp65 and TNF-α protein expression from SAMP8 compared to SAMR1 mice. In liver, the combined intervention significantly restored p-Aktser473, p-eIF2α and p-JNK protein expression. In both EPI and SC fat, the combined intervention is effective for reducing p-NF-κB p65 and TNF-α in both fat depot, while only partially reduced ER stress markers in SC fat. As for adiponectin, their combination is unable to reverse reduction in adiponectin level. Adiponectin secretion in SC fat from VD, RSV and VDRSV group were also significantly reduced compared to SAMR1. CONCLUSION: The combined intervention might exert greater beneficial effects for reversing aging associated metabolic dysfunction in liver and adipose tissue from SAMP8 mice.

Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice.

BACKGROUND: Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment. OBJECTIVE: We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms. METHOD: SAMP8 mice and their control senescence-accelerated mouse resistant 1 (SAMR1) mice (10 weeks old) were divided into 5 groups, i.e. SAMR1 group, SAMP8 group, SAMP8 mice supplemented with VD group, SAMP8 mice supplemented with RSV group and SAMP8 mice supplemented with both VD and RSV group. At the end of the intervention, Morris water maze (MWM) test was used to assess cognitive function. Hippocampus and parietal cortex were dissected for further analysis. RESULTS: The combination of VD and RSV significantly increased time spent in target quadrant and the number of crossing via MWM test. In hippocampus, the combined intervention significantly reduced soluble Aß42 level and BACE1 protein expression. In cortex, the combined treatment significantly reduced phosphorylation of tau at serine404 and p-p53, as well as enhanced p-CREB protein expression. The combination also significantly reduced GFAP and p-NFκB p65 in both hippocampus and cortex. CONCLUSION: The combined intervention might exert greater neuroprotective effects in SAMP8 mice, this might be associated with the fact that the combined intervention could positively affect amyloidogenic pathways, neuroinflammation, tau phosphorylation and probably apoptosis markers.

The combination of 1α,25dihydroxyvitaminD3 with resveratrol improves neuronal degeneration by regulating endoplasmic reticulum stress, insulin signaling and inhibiting tau hyperphosphorylation in SH-SY5Y cells.

Endoplasmic reticulum (ER) stress is a critical factor involved in the pathogenesis of Alzheimer's disease (AD). Vitamin D and resveratrol are two nutritional factors that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. We aimed to determine the effects of vitamin D & resveratrol on ER stress mediated neurodegeneration and whether synergistic effects existed. Tunicamycin and Aß25-35 was utilized to induce ER stress in SH-SY5Y cells, cells were then incubated with vitamin D and resveratrol. The combination of vitamin D & resveratrol completely reversed tunicamycin and Aß25-35 induced cytotoxicity in SH-SY5Y cells, as well as elevation in ER stress markers (i.e.GRP78, p-eIF2α and CHOP), insulin signaling disruption (i.e. elevation in p-IRS-1serine307 and reduction in p-Akt serine473) and tau phosphorylation (i.e. reduction in p-GSK3ß serine9, and elevation in p-Tau serine396 &404). Further studies are required to clarify whether the observed synergistic effects in the present study would also existed in vivo, this will lay scientific foundation whether the combination of vitamin D with resveratrol might be an effective maneuver in the treatment of AD in human subjects.