Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia. Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory. Materials and methods Rats were pretreated with metformin (200 mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured. Results Pretreatment with metformin (met) in the met + ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p < 0.001) and increased latency time compared with the I/R group (p < 0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R + met group (p < 0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p < 0.001) but increased that compared with the sham group (p < 0.001). The level of pro-BDNF decreased in the met + CC + I/R group compared with the met + I/R group (p < 0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p < 0.001). Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK. © 2016 Informa UK Limited, trading as Taylor & Francis Group

The Effects of Flaxseed Oil Omega-3 Fatty Acids Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract Objective This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome (PCOS). Methods: This randomized double-blind, placebo-controlled trial was conducted on 60 women with PCOS according to the Rotterdam criteria aged 18–40 years old. Participants were randomly assigned into two groups to receive either 1,000 mg flaxseed oil omega-3 fatty acids (n=30) or placebo (n=30) twice a day for 12 weeks. Metabolic, endocrine, inflammatory factors were quantified at baseline and after the 12-week intervention. Results: After the 12-week intervention, compared to the placebo, flaxseed oil omega-3 supplementation significantly decreased insulin values (−2.6±7.7 vs.+1.3±3.9 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (−0.7±1.7 vs.+0.3±0.9, P=0.01), mF-G scores (−1.2±1.7 vs. -0.1±0.4, P=0.001), and increased quantitative insulin sensitivity check index (+0.01±0.02 vs. −0.01±0.02, P=0.01). In addition, supplementation with flaxseed oil omega-3 resulted in significant decreases in serum triglycerides (−5.1±20.9 vs.+9.7±26.1 mg/dL, P=0.01), VLDL-cholesterol (−1.0±4.2 vs.+1.9±5.2 mg/dL, P=0.01) and high-sensitivity C-reactive protein (hs-CRP) (−1.6±3.1 vs.+0.2±1.5 mg/L, P=0.004) compared to the placebo. We did not see any significant effect of flaxseed oil omega-3 supplementation on hormonal and other lipid profiles, and plasma nitric oxide levels. Conclusions: Overall, flaxseed oil omega-3 supplementation for 12 weeks in women with PCOS had beneficial effects on insulin metabolism, mF-G scores, serum triglycerides, VLDL-cholesterol and hs-CRP levels, but did not affect hormonal and other lipid profiles, and plasma nitric oxide levels. Key words: Flaxseed oil supplementation - metabolic status - polycystic ovary syndrome