Placental lipid metabolism in preeclampsia.

OBJECTIVES: The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia. METHODS: The current study includes normotensive control women (n = 40) and women with preeclampsia (n = 39). Preeclampsia women were further classified into women delivering at term preeclampsia (T-PE; n = 15) and preterm preeclampsia (PT-PE; n = 24). RESULTS: There were no significant differences in maternal lipid profile between the T-PE and normotensive control groups. Maternal plasma VLDL (P < 0.05) and ratios of total cholesterol : HDL (P < 0.05), atherogenic index [log (triglycerides/HDL)] (P < 0.01) and apolipoprotein B : apolipoprotein A (P < 0.05) were higher in the PT-PE group as compared with the normotensive control group. Placental total cholesterol and HDL levels were higher (P < 0.05) in the T-PE as compared with the normotensive control group. Higher placental triglycerides (P < 0.05) were observed in PT-PE group compared with T-PE group. Placental mRNA levels of peroxisome proliferator activated receptor α, carnitine palmitoyl transferase-1, cluster of differentiation 36 and lipoprotein lipases were lower (P < 0.05) in the PT-PE than normotensive control group. A negative association of mRNA levels of peroxisome proliferator activated receptor α (r = -0.246, P = 0.032; r = -0.308, P = 0.007, respectively), carnitine palmitoyl transferase-1 (r = -0.292, P = 0.011; r = -0.366, P = 0.001), lipoprotein lipases (r = -0.296, P = 0.010; r = -0.254, P = 0.028) with SBP and DBP was observed. There was a positive association of placental triglycerides (r = 0.244, P = 0.031) with DBP. CONCLUSION: Women with preeclampsia exhibit higher lipid : lipoprotein ratios suggesting an atherogenic state particularly in women delivering preterm. Lower expression of genes involved in placental fatty acid oxidation and transport was also observed in preeclampsia.

Leptin as a predictive marker for metabolic syndrome.

Metabolic syndrome poses a major threat on human health affecting the quality of life. Adipose tissue is an important organ which plays a crucial role in the pathogenesis of metabolic syndrome. Adipocytokines secreted by the adipose tissue plays a critical role in storage, food intake, energy expenditure, lipid and glucose metabolism. Leptin is primarily involved in regulating food intake, body weight and energy homeostasis through neuroendocrine functions. Contemporary research suggests that leptin also influences insulin sensitivity and lipid metabolism. High leptin concentrations are directly associated with the obesity subsequent development of metabolic disease sequelae such as insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidation of the mechanism of action of leptin would help to develop novel therapeutic approaches for there metabolic disorders like obesity and diabetes. This review provides an updated 'state-of-the-art' about the leptin and its role in the pathophysiology of metabolic syndrome at the molecular level.

Adiponectin: A potential therapeutic target for metabolic syndrome.

Adiponectin is an important adipocytokine secreted chiefly by fat containing adipocytes, and plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress. Alterations in adiponectin levels have been shown to directly affect lipid and glucose metabolism that further increase the synthesis of lipids, free fatty acids and inflammatory cytokines. Changes in adiponectin levels also contribute to insulin resistance, obesity, cardiovascular diseases and type 2 diabetes. In the present review, we provide a comprehensive evaluation of the role of adiponectin and its molecular mechanisms in metabolic syndrome. Clinical improvement in adiponectin levels have been shown to positively modulate lipid and glucose metabolism, thus further substantiating its role in regulation of lipid and glucose metabolism. Currently adiponectin is being investigated as a potential therapeutic target for metabolic syndrome, although more research is required to understand the underlying mechanisms controlling adiponectin levels, including dietary and lifestyle interventions, that may target adiponectin as a therapeutic intervention in metabolic syndrome.

Attenuation of glycation-induced multiple protein modifications by Indian antidiabetic plant extracts.

CONTEXT: Protein glycation is the major contributing factor in the development of diabetic complications. The antiglycation potential of medicinal plants provides a promising opportunity as complementary interventions for complications. OBJECTIVE: To investigate the antiglycation potential of 19 medicinal plants extracts using albumin by estimating different indicators: (1) glycation (early and late), (2) albumin oxidation, and (3) amyloid aggregation. MATERIALS AND METHODS: The effect of aqueous plant extracts (1% w/v) on protein glycation was assessed by incubating albumin (10 mg/mL) with fructose (250 mM) for 4 days. Degree of protein glycation in the absence and presence of plant extracts was assessed by estimating fructosamine, advanced glycation end products (AGEs), carbonyls, free thiol group and ß-amyloid aggregation. RESULTS: Petroselinum crispum, Boerhavia diffusa, Terminalia chebula, Swertia chirayita and Glycyrrhiza glabra showed significant antiglycating activity. P. crispum and A. barbadensis inhibited the carbonyl stress and protected the thiol group from oxidative damage. There was significant correlation between protein thiols and amyloid inhibition (R = -.69, p < .001). CONCLUSION: P. crispum, B. diffusa and T. chebula had the most potent antiglycation activity. These plant exerted noticeable antiglycation activity at different glycation modifications of albumin. These findings are important for identifying plants with potential to combat diabetic complications.

Effect of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in rats: A multigeneration study.

Vitamin B12 and omega-3 fatty acids are important nutrients required for neuronal functioning. We have demonstrated the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in the first and second generation offspring. However, there is a need to examine if the effects are sustained in the third generation offspring. This study reports the effects of vitamin B12 and omega-3 fatty acid supplementation across three consecutive generations on brain neurotrophins like brain derived neurotrophic factor (BDNF); nerve growth factor (NGF) and cognitive performance in the third generation male offspring. Three successive generations of Wistar rats were assigned the following groups throughout pregnancy, lactation and adulthood: i) Control, ii) vitamin B12 deficient (BD), iii) vitamin B12 deficient + omega-3 fatty acid (BDO), iv) vitamin B12 supplemented (BS) and v) vitamin B12 supplemented + omega-3 fatty acid (BSO). The BD group demonstrated lower (p < 0.01) NGF in the cortex but not BDNF levels although the cognition was impaired (p < 0.01). In contrast, in the BDO group, higher NGF levels were observed in the hippocampus and animals demonstrated improved (p < 0.01) cognitive performance. Vitamin B12 supplementation showed comparable BDNF levels in the hippocampus while their levels were lower in the cortex as compared to the control (p < 0.05). These animals showed more reference and working memory errors (p < 0.01) as compared to the control group. A combined supplementation of vitamin B12 and omega-3 fatty acid showed higher (p < 0.01) levels of DHA and NGF in the hippocampus, higher BDNF in both hippocampus and cortex and improved cognitive performance. Our findings have implications for fortification of foods with vitamin B12 and omega-3 fatty acids in improving brain development.

Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.

In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function.

Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring.

Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth.

Vitamin B12 and omega-3 fatty acids are critical for normal brain development and function and their deficiencies during pregnancy could have adverse effects on cognitive performance in children. Our earlier studies indicate that both maternal vitamin B12 and omega-3 fatty acids influence brain development by regulating the levels of neurotrophins. Literature suggests that there exists a cross talk between neurotrophins like nerve growth factor (NGF) and angiogenic factors like vascular endothelial growth factor (VEGF). It remains to be established whether maternal nutrients like vitamin B12 and omega-3 fatty acids influence the levels of angiogenic markers like VEGF and NGF in the brain of the offspring. Therefore the present study examines the effect of maternal vitamin B12 and omega-3 fatty acids on protein and mRNA levels of VEGF, HIF-1 alpha (hypoxia inducible factor alpha) and NGF in the pup brain at birth. Pregnant Wistar rats were divided into five dietary groups (n=8 each): control, vitamin B12 deficient, vitamin B12 deficient+omega-3 fatty acid, vitamin B12 supplemented, vitamin B12 supplemented+omega-3 fatty acid. At birth the pups were dissected to collect the brain tissue. Maternal vitamin B12 deficiency showed lower (p<0.05) pup brain mRNA and protein levels (p<0.01) of VEGF, higher (p<0.01) HIF-1 alpha protein levels, lower (p<0.05) NGF protein levels while NGF mRNA levels were not altered. Omega-3 fatty acid supplementation to a vitamin B12 deficient group normalized the VEGF mRNA levels, NGF protein levels and HIF-1 alpha protein levels. Vitamin B12 supplementation showed similar protein and mRNA levels of VEGF and NGF as well as HIF-1 alpha protein levels as compared to control. Omega-3 fatty acid supplementation to the vitamin B12 supplemented group showed higher (p<0.01) protein and mRNA levels of NGF but the protein and mRNA levels of VEGF were comparable to control. In conclusion maternal vitamin B12 and omega-3 fatty acids both influence the levels and expression of neurotrophins and angiogenic factors in the offspring brain suggesting a possible benefit of combined maternal supplementation of these vital nutrients.

Aqueous extract of some indigenous medicinal plants inhibits glycation at multiple stages and protects erythrocytes from oxidative damage-an in vitro study.

Azadirachta indica, Emblica officinalis, Syzygium cumini and Terminalia bellirica are common in Indian system of traditional medicine for the prevention of diabetes and its complications. The aim of the present study was to comprehensively and comparatively investigate the antiglycation potential of these plant extracts at multiple stages and their possible protective effect against glycated albumin mediated toxicity to erythrocytes. Antiglycation activities of these plant extracts was measured by co-incubation of plant extract with bovine serum albumin-fructose glycation model. The multistage glycation markers- fructosamines (early stage), protein carbonyls (intermediate stage) and AGEs (late stage) are investigated along with measurement of thiols and ß aggregation of albumin using amyloid-specific dyes-Congo red and Th T. Protection of erythrocytes from glycated albumin induced toxicity by these plant extracts was assessed by measuring erythrocytes hemolysis, lipid peroxidation, reduced glutathione and intracellular antioxidant capacity. Total phenolics, reducing power and antioxidant activities of the plant extracts were also measured. In vitro glycation assays showed that plant extracts exerted site specific inhibitory effects at multiple stages, with T. bellirica showing maximum attenuation. In erythrocytes, along with the retardation of glycated albumin induced hemolysis and lipid-peroxidation, T. bellirica considerably maintained cellular antioxidant potential. Significant positive correlations were observed between erythrocyte protection parameters with total phenolics. These plant extracts especially T. bellirica prevents glycation induced albumin modifications and subsequent toxicity to erythrocytes which might offer additional protection against diabetic vascular complications.

Nutraceutical properties of dietary plants extracts: prevention of diabetic nephropathy through inhibition of glycation and toxicity to erythrocytes and HEK293 cells.

CONTEXT: Glycated albumin is reported to elicit pathobiologic effects in diabetic nephropathy and abrogating its biologic effects has novel therapeutic potential. OBJECTIVE: This study examines the effects of dietary plants extracts (Laurus nobilis, Carum carvi, Coccinia grandis, Mentha arvensis, Phaseolus vulgaris) against albumin glycation and its toxicity to erythrocytes and HEK293 cells. MATERIALS AND METHODS: Albumin (10 mg/ml) was incubated with fructose (250 mM) in PBS along with aqueous plant extracts (1% w/v) for 4 d. After incubation, the antiglycation potential of extracts was estimated by measuring AGEs, fructosamine, amyloids, carbonyls, free amino groups, and antioxidant potential of albumin. The glycation extent of the treated samples was determined by boronate affinity chromatography. Effect of extracts against glycation induced cytotoxicity in erythrocytes and HEK 293 cells was assessed by estimating viability, glutathione, and antioxidant capacity. Plant extracts were tested for their phenolic content and antioxidant potential (reducing potential, DPPH, ABTS, NO, and H2O2 radical scavenging activities). RESULTS: Plant extracts significantly decreased the AGEs formation and amyloid aggregation in glycated BSA (p < 0.001). Further, fructosamine and carbonyls were reduced to 55-72% and 83-89%, respectively. Free amino group and antioxidant activity of albumin were also preserved by 1.25-1.40-fold and 1.75-1.8-fold, respectively. Further, co-incubation of extracts with glycated albumin, protected erythrocytes, and HEK293 cells as they inhibited cellular hemolysis/toxicity (p < 0.001) by upregulating cellular antioxidants. DISCUSSION AND CONCLUSION: Plant co-incubation reversed many modifications in albumin glycation, cellular dysfunction indicating that dietary sources with antiglycating and antioxidant potential could be considered for the effective management of diabetic nephropathy.