A single bout of cycling exercise induces nucleosome repositioning in the skeletal muscle of lean and overweight/obese individuals.

AIM: To compare the molecular and metabolic effects of a single exercise bout in the skeletal muscle between lean and overweight/obese (Ov/Ob) individuals. MATERIALS AND METHODS: Participants recruited were men, aged 19-30 years, who were either lean (body mass index [BMI] < 25, 18.5-24.1 kg/m2 ; n = 15) or Ov/Ob (BMI ≥ 25, 25.5-36.9 kg/m2 ; n = 15). Four hours after a high-carbohydrate breakfast (7 kcal/kg; 60% carbohydrate, 25% fat, 15% protein), participants performed a cycling exercise (50% VO2 max, expending ~650 kcal). Muscle biopsies and peripheral blood samples were collected 30 minutes before the meal and immediately after exercise. Blood analysis, and muscle acylcarnitine profiles, transcriptomics, and nucleosome mapping by micrococcal nuclease digestion with deep sequencing were performed. RESULTS: A single exercise bout improved blood metabolite profiles in both lean and Ov/Ob individuals. Muscle long-chain acylcarnitines were increased in Ov/Ob compared with lean participants, but were not altered by exercise. A single exercise bout increased the mRNA abundance of genes related to mitochondria and insulin signalling in both lean and Ov/Ob participants. Nucleosome mapping by micrococcal nuclease digestion with deep sequencing revealed that exercise repositioned the -1 nucleosome away from the transcription start site of the PGC1a promoter and of other mitochondrial genes, but did not affect genes related to insulin signalling, in both lean and Ov/Ob participants. CONCLUSION: These data suggest that a single exercise bout induced epigenetic alterations in skeletal muscle in a BMI-independent manner.

Skeletal Muscle Nucleo-Mitochondrial Crosstalk in Obesity and Type 2 Diabetes.

Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation and accumulation of fatty acid intermediates in the form of long and medium chain acylcarnitines, may contribute to ectopic lipid deposition and insulin resistance during high fat diet (HFD)-induced obesity. The present review discusses the roles of anterograde and retrograde communication in nucleo-mitochondrial crosstalk that determines skeletal muscle mitochondrial adaptations, specifically alterations in mitochondrial number and function in relation to obesity and insulin resistance. Special emphasis is placed on the effects of high fat diet (HFD) feeding on expression of nuclear-encoded mitochondrial genes (NEMGs) nuclear receptor factor 1 (NRF-1) and 2 (NRF-2) and peroxisome proliferator receptor gamma coactivator 1 alpha (PGC-1α) in the onset and progression of insulin resistance during obesity and how HFD-induced alterations in NEMG expression affect skeletal muscle mitochondrial adaptations in relation to beta oxidation of fatty acids. Finally, the potential ability of acylcarnitines or fatty acid intermediates resulting from mitochondrial beta oxidation to act as retrograde signals in nucleo-mitochondrial crosstalk is reviewed and discussed.

Higher intake of certain nutrients among older adults is associated with better cognitive function: an analysis of NHANES 2011-2014.

BACKGROUND: An increasing number of adults are over the age of 65, and there is concern about the increasing prevalence of age-associated cognitive decline and poor mental health status in older adults in the United States. Several nutrients are known to have important biological roles in brain health and neurological function, but many individuals fall short of recommended intake levels. The objective of this study was to examine the association between nutrient intake and cognitive function. We also explored whether nutrient intake was associated with depression. METHODS: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and included participants ≥ 60 years of age who had reliable day 1 dietary recall data and either valid cognitive function data (n = 2713) or valid depression score data (n = 2943). The sample was stratified by gender, and cognitive functioning test (CFT) composite z-scores were analyzed by quartiles. Depression status was assessed using the Patient Health Questionnaire (PHQ-9). RESULTS: Higher intake and adequacy of a number of different nutrients from food were associated with higher cognitive function in both males and females. Nutrients that showed the most consistent associations with cognitive function across intake and adequacy analyses for food in both males and females were vitamin A, vitamin E, thiamin, riboflavin, vitamin B6, folate, magnesium, potassium, zinc, vitamin K, and lutein and zeaxanthin (p < 0.05 for all). These associations were positive with increasing intake and adequacy being associated with higher CFT composite z-scores. Analysis of nutrient intake and depression yielded results that differed by gender. In females, the nutrients that showed consistent inverse associations with depression scores across both intake and adequacy analyses for food were vitamin A, vitamin C, magnesium, vitamin K, potassium, and dietary fiber (p < 0.05 for all). In males, no significant associations between nutrient intake from food and depression scores were observed. CONCLUSIONS: Our findings suggest that older adults with sufficient intakes of certain essential nutrients have higher cognitive function. Future studies are needed to confirm whether a well-balanced diet and/or dietary supplements which emphasize these nutrients are effective for prevention of age-related declines in cognitive function and mood.

Lower Intakes of Key Nutrients Are Associated with More School and Workplace Absenteeism in US Children and Adults: A Cross-Sectional Study of NHANES 2003-2008.

The influence of individual macro- and micronutrients on absenteeism in the United States is largely unknown. The objective of this study was to determine whether nutritional status or nutrient intake were associated with absenteeism from school and work due to illness or injury. Data from NHANES 2003-2008 were used to assess nutrient intake from food and food plus supplements, nutritional biomarker levels, and school and work absenteeism per year in children and adults. Negative binomial regression models were used to predict mean days of missed work per year and to estimate incidence rate ratios (IRRs) of absenteeism by nutrient biomarker status. Of 7429 children, 77% reported missing school days (mean 4.0 days). Of 8252 adults, 51% reported missing work days (mean 4.9 days). Children and adults who reported more absent days had a significantly lower intake of protein and several essential micronutrients from the diet. When nutrients from supplements were included, this negative association was retained for protein, selenium, choline, and DHA in children and for protein, selenium, vitamin K, choline, potassium, fiber, octadecatrienoic acid, and lycopene in adults. Future studies are needed to ascertain whether dietary interventions, such as access to healthier food options and/or dietary supplements, can reduce absenteeism.

The association of the Affordable Care Act with nutrient consumption in adults in the United States.

The Patient Protection and Affordable Care Act, more commonly known as the ACA, was legislation passed in the United States in 2010 to expand access to health insurance coverage for millions of Americans with a key emphasis on preventive care. Nutrition plays a critical role in overall wellness, disease prevention and resilience to chronic illness but prior to the ACA many Americans did not have adequate health insurance coverage to ensure proper nutrition. With passage of the ACA, more individuals received access to nutritional counseling through their primary care physicians as well as prescription vitamins and supplements free of charge. The objective of this study was to evaluate the impact of a national health insurance reform on nutrient intake among general population, including more vulnerable low-income individuals and patients with chronic conditions. Using data from the National Health and Nutrition Examination Survey (NHANES), we identified 8,443 adults aged 21 years and older who participated in the survey before (2011-2012) and after the ACA (2015-2016) implementation and conducted a subgroup analysis of 952 respondents who identified as Medicaid beneficiaries and 719 patients with a history of cancer. Using pre-post study design and bivariate and multivariable logistic analyses, we compared nutrient intake from food and supplementation before and after the ACA and identified risk factors for inadequate intake. Our results suggest that intake of micronutrients found in nutrient-dense foods, mainly fruit and vegetables, has not changed significantly after the ACA. However, overall use of nutritional supplements increased after the ACA (p = 0.05), particularly magnesium (OR = 1.02), potassium (OR = 0.76), vitamin D (both D2, and D3, OR = 1.34), vitamin K (OR = 1.15) and zinc (OR = 0.83), for the general population as well as those in our subgroup analysis Cancer Survivors and Medicaid Recipients. Given the association of increased use of nutritional supplements and expansion of insurance access, particularly in our subgroup analysis, more research is necessary to understand the effect of increasing access to nutritional supplements on the overall intake of micro- and macronutrients to meet daily nutritional recommended allowances.

Association of omega-3 levels and sleep in US adults, National Health and Nutrition Examination Survey, 2011-2012.

OBJECTIVE: To determine associations between serum long-chain (LC) omega-3 fatty acid levels and sleep parameters among adults (N = 1314) in NHANES 2011-2012. METHODS: Regression analyses accounting for the complex-survey design were used to assess associations between serum LC omega-3 fatty acid levels, sleep duration, difficulty falling sleeping and sleep disorder. RESULTS: Overall, 48.6% were male, the mean age was 47.2 years, 5% reported very short sleep, 29% short sleep, 63% normal sleep and 3% long sleep. The sum of LC omega-3 fatty acid levels was lower among adults with short versus normal sleep, although differences were attenuated with adjustment for sociodemographic factors. Relative to normal sleep, adults with very short sleep had lower levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and sum of LC omega-3 fatty acids. Differences remained significant (p < .05 for all) with adjustment for sociodemographic factors. No associations were observed with difficulty falling sleeping or sleep disorder. CONCLUSION: Our results suggest that omega-3 fatty acid levels are associated with healthy sleep duration, although, interventions are needed to clarify causality.

Socioeconomic Inequalities Impact the Ability of Pregnant Women and Women of Childbearing Age to Consume Nutrients Needed for Neurodevelopment: An Analysis of NHANES 2007-2018.

Adequate consumption of nutrients that support infant neurodevelopment is critical among pregnant women and women of childbearing age. Understanding the potential effects of socioeconomic inequalities on nutrient gaps in these life stages is thus important for informing strategies to mitigate negative health consequences. Usual intake (foods and dietary supplements) of neurodevelopment-related nutrients was determined from 24 h recalls among women of childbearing age and pregnant women (20−44 years) using data from 2007−2018 NHANES. Usual intake was compared across household food security, poverty-to-income ratio (PIR), and household participation in federal food and nutrition assistance programs. Intake of EPA + DHA was universally low with >95% of all women (pregnant and non-pregnant) below the DGA recommendation from foods alone. Women in households that participated in the Supplemental Nutrition Assistance Program had a significantly lower intake of multiple nutrients relative to those who did not participate. For example, 50% had intakes below the estimated average requirement (EAR) for vitamin A (versus 32%), 42% were below the EAR for calcium (versus 33%) and 65% were below the EAR for magnesium (versus 42%). Similar gradients were observed by PIR and household food security, and among pregnant women whereby gaps were more evident in those experiencing socioeconomic inequalities. The use of dietary supplements attenuated shortfalls for most nutrients. These findings highlight a critical need to support the nutritional requirements for women of childbearing age and pregnant women.

Long-chain omega-3 fatty acid serum concentrations across life stages in the USA: an analysis of NHANES 2011-2012.

OBJECTIVE: To determine reference ranges of circulating long-chain (LC) omega-3 fatty acids: eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in a nationally representative population of Americans. To provide context, serum concentrations of LC omega-3 were compared with concentrations associated with consuming the recommended amount of EPA and DHA by the Dietary Guidelines for Americans (DGA) and the Omega-3 Index (EPA+DHA). DESIGN: Cross-sectional population-based study. SETTING: The National Health and Nutrition Examination Survey 2011-2012 cycle. PARTICIPANTS: Participants with fatty acids measured in serum: 945 children, age 3-19 years, and 1316 adults, age 20 and older. MAIN MEASURE: Serum EPA, DPA, DHA and sum of LC omega-3 fatty acids expressed as per cent of total fatty acids. RESULTS: Among children, mean (SE) serum concentrations of EPA, DHA and omega-3s were 0.28% (0.01), 1.07% (0.02) and 1.75% (0.03). Among adults, mean (SE) of EPA, DHA and omega-3s were 0.61% (0.02), 1.38% (0.05) and 2.43% (0.08), all of which were significantly higher than corresponding serum fatty acid concentrations in children (p<0.001). Despite recommendations for higher intake, pregnant and/or breastfeeding women had mean (SE) EPA, DHA and LC omega-3 concentrations of 0.34% (0.07), 1.52% (0.08) and 2.18% (0.15), which were comparable to women of childbearing age; p=0.17, p=0.10 and p=0.73. Over 95% of children and 68% of adults had LC omega-3 concentrations below those associated with the DGA recommendation. Approximately 89% of adults had an Omega-3 Index in the high cardiovascular risk category. CONCLUSIONS: Contemporary reference ranges for circulating LC omega-3s are critical for setting public health recommendations. Our findings show the need for continued emphasis on regular consumption of LC omega-3s among Americans, particularly considering the importance of LC omega-3s in cardiovascular health, brain health and development throughout life.

Total estimated usual nutrient intake and nutrient status biomarkers in women of childbearing age and women of menopausal age.

BACKGROUND: Women of childbearing age (WCBA) and women of menopausal age (WMENO) have distinct nutritional needs. Understanding nutrient intake and status in these life stages is critical for tailoring dietary recommendations. OBJECTIVES: The objectives of this study were to evaluate total estimated usual nutrient intakes from food and food plus supplements and to compare these to established recommendations for WCBA and WMENO life stages and examine associations between self-reported estimated usual intakes and nutrient status biomarkers. METHODS: Twenty-four-hour dietary recall data from 2011-2016 NHANES were used to estimate usual intake of nutrients from food and food plus supplements for WCBA (aged 15-44 y, n = 4,134) and WMENO (aged 40-65 y, n = 3,438). Estimates of mean usual intake were derived and compared across clinically defined nutrient biomarker categories. RESULTS: Both young (aged 15-30 y) and older (aged 31-44 y) WCBA had intakes from food below the Estimated Average Requirement (EAR) for calcium (49% and 44%, respectively), magnesium (62%, 44%), and vitamins A (50%, 44%), C (47%, 46%), D (>97%, >97%), and E (92%, 88%). Similarly, perimenopausal (aged 40-50 y) and menopausal (aged 51-65 y) women had intakes from food below the EAR for calcium (48% and 74%, respectively), magnesium (50%, 49%), and vitamins A (44%, 37%), C (44%, 41%), D (>97%, >97%), and E (88%, 86%). Nutrient gaps decreased with supplement usage. For folate, vitamins D and B-12, and DHA, women in the lowest biomarker category (indicating increased risk of deficiency) had significantly lower intake from food (315.2 ± 25.9 compared with 463.8 ± 5.2 µg dietary folate equivalents, 3.5 ± 0.1 compared with 4.2 ± 0.1 µg, 3.6 ± 0.2 compared with 4.3 ± 0.1 µg, and 0.037 ± 0.005 compared with 0.070 ± 0.006 g, respectively; P < 0.01) of the corresponding nutrient compared with the highest biomarker category. CONCLUSIONS: Substantial percentages of WCBA and WMENO are not meeting recommendations for multiple nutrients, whereas supplement usage partially fills nutrient gaps. Dietary intake was positively associated with most nutrient status biomarkers. Specific guidance is needed to ensure adequate nutrient intakes and nutrient status during these critical life stages.

Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES.

A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005-2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.-specifically in critical nutrients that support immune health-public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.

Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia.

Omega-3 fatty acids, particularly docosahexaenoic fatty acid (DHA), are widely recognized to impact fetal and infant neurodevelopment. The impact of DHA on brain development, and its inefficient synthesis from the essential alpha-linolenic acid (ALA), has led to recommended DHA intakes of 250-375 mg eicosapentaenoic acid + DHA/day for pregnant and lactating women by the Dietary Guidelines for Americans. Despite these recommendations, the intake of omega-3s in women of child-bearing age in the US remains very low. The low maternal status of DHA prior to pregnancy could impair fetal neurodevelopment. This review focuses on maternal omega-3 status in conditions of gestational diabetes mellitus (GDM) and preeclampsia, and the subsequent impact on placental transfer and cord blood concentration of omega-3s. Both GDM and preeclampsia are associated with altered maternal omega-3 status, altered placental omega-3 metabolism, reduced cord blood omega-3 levels and have an impact on neurodevelopment in the infant and on brain health later in life. These findings indicate lower DHA exposure of the developing baby may be driven by lower placental transfer in both conditions. Thus, determining approaches which facilitate increased delivery of DHA during pregnancy and early development might positively impact brain development in infants born to mothers with these diseases.

Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression.

Pgc-1α and its various isoforms may play a role in determining skeletal muscle mitochondrial adaptations in response to diet. 8 wks of dietary supplementation with the flavonoid quercetin (Q) or red onion extract (ROE) in a high fat diet (HFD) ameliorates HFD-induced obesity and insulin resistance in C57BL/J mice while upregulating Pgc-1α and increasing skeletal muscle mitochondrial number and function. Here, mice were fed a low fat (LF), high fat (HF), high fat plus quercetin (HF + Q), or high fat plus red onion extract (HF + RO) diet for 9 wks and skeletal muscle Pgc-1α isoform expression and DNA methylation were determined. Quantification of various Pgc-1α isoforms, including isoforms Pgc-1α-a, Pgc-1α-b, Pgc-1α-c, Pgc-1α4, total NT-Pgc-1α, and FL-Pgc-1α, showed that only total NT-Pgc-1α expression was increased in LF, HF + Q, and HF + RO compared to HF. Furthermore, Q supplementation decreased Pgc-1α-a expression compared to LF and HF, and ROE decreased Pgc-1α-a expression compared to LF. FL-Pgc-1α was decreased in HF + Q and HF + RO compared to LF and HF. HF exhibited hypermethylation at the -260 nucleotide (nt) in the Pgc-1α promoter. Q and ROE prevented HFD-induced hypermethylation. -260 nt methylation levels were associated with NT-Pgc-1α expression only. Pgc-1α isoform expression may be epigenetically regulated by Q and ROE through DNA methylation.

Dietary flaxseed oil and fish oil ameliorates renal oxidative stress, protein glycation, and inflammation in streptozotocin-nicotinamide-induced diabetic rats.

Protective and prophylactic effects of omega-3 fatty acids on oxidative stress and inflammation are well known. We assessed beneficial effects of flaxseed oil and fish oil on streptozotocin (65 mg/kg; i.p.)-nicotinamide (110 mg/kg; i.p.) induced diabetic rats by studying renal expression of antioxidant and inflammatory genes. Diabetic rats given 10 % flaxseed oil or 10 % fish oil diet for 35 days showed significant decrease in renal lipid peroxidation. Flaxseed oil diet resulted in up-regulation of renal superoxide dismutase-1 (SOD-1) (activity and expression) and glutathione peroxidase-1 (GPx-1) expression. Furthermore, both diets up-regulated catalase (CAT) (activity and expression) and down-regulated heme oxygenase-1 (HO-1) expression. Both diets were able to limit the renal advanced glycation end products (AGEs) formation and reduced receptor of AGE (RAGE) protein expression significantly. Expressions of interleukin-6 (IL-6) and NF-κB p65 subunit were down-regulated significantly by flaxseed oil or fish oil diet. The histological tubular injuries were also lowered by both diets. These results suggest that dietary ω-3 fatty acids may slow the progression of diabetic nephropathy (DN) associated with oxidative stress, glycation, and inflammation in the kidney.

Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning.

BACKGROUND AND PURPOSE: Sodium butyrate (NaB), an epigenetic modifier, is effective in promoting insulin sensitivity. The specific genomic loci and mechanisms underlying epigenetically induced obesity and insulin resistance and the targets of NaB are not fully understood. EXPERIMENTAL APPROACH: The anti-diabetic and anti-obesity effects of NaB treatment were measured by comparing phenotypes and physiologies of C57BL/6J mice fed a low-fat diet (LF), high-fat diet (HF) or high-fat diet plus NaB (HF + NaB) for 10 weeks. We determined a possible mechanism of NaB action through induction of beneficial skeletal muscle mitochondrial adaptations and applied microccocal nuclease digestion with sequencing (MNase-seq) to assess whole genome differences in nucleosome occupancy or positioning and to identify associated epigenetic targets of NaB. KEY RESULTS: NaB prevented HF diet-induced increases in body weight and adiposity without altering food intake or energy expenditure, improved insulin sensitivity as measured by glucose and insulin tolerance tests, and decreased respiratory exchange ratio. In skeletal muscle, NaB increased the percentage of type 1 fibres, improved acylcarnitine profiles as measured by metabolomics and produced a chromatin structure, determined by MNase-seq, similar to that seen in LF. Targeted analysis of representative nuclear-encoded mitochondrial genes showed specific repositioning of the -1 nucleosome in association with altered gene expression. CONCLUSIONS AND IMPLICATIONS: NaB treatment may be an effective pharmacological approach for type 2 diabetes and obesity by inducing -1 nucleosome repositioning within nuclear-encoded mitochondrial genes, causing skeletal muscle mitochondrial adaptations that result in more complete ß-oxidation and a lean, insulin sensitive phenotype.

'Ashvagandharishta' prepared using yeast consortium from Woodfordia fruticosa flowers exhibit hepatoprotective effect on CCl4 induced liver damage in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Consortium of yeasts sourced from traditionally used Woodfordia fruticosa flowers proved to be beneficial for fermenting Ashvagandharishta. It resulted in faster fermentation, acceptable organoleptic properties and demonstrable hepatoprotective potential in CCl4 induced hepatotoxicity. To formulate Ashvagandharishta using consortium of yeasts and to investigate its physiochemical parameters. Standardize the formulation with the help of standard withaferin-A and withanolide-A and to evaluate its hepatoprotective potential in CCl4 induced hepatotoxicity in the rat model. MATERIAL AND METHODS: Ashvagandharishta was prepared using a 5% consortium of yeasts and ascertained its quality through physiochemical and phytochemical investigation. Withaferin-A and withanolide-A was simultaneously estimated by HPLC for standardization. Hepatoprotective potential was evaluated by administering 2.31 and 1.15 ml/kg doses while considering biochemical parameters like serum AST, ALT, ALP and lipid profile. Gene expression study was carried out for the expression of antioxidant and inflammatory genes such as CAT, GPx and proinflammatory gene IL-6. Histopathology of liver was also studied with the help of H&E staining. RESULTS: Ashvagandharishta was found organolepticaly acceptable with optimized physiochemical parameters. Withaferin-A and withanolide-A in Ashvagandharishta estimated as 0.3711, 0.7426 (%w/v), respectively. In the CCl4 induced hepato-toxicity model, Ashvagandharishta-2.31ml/kg dose showed significant decrease in elevated hepatic level of AST(p<0.001), ALT(p<0.01) and ALP(p<0.001). Both doses of Ashvagandharishta showed significant reduction of TG, Cholesterol, VLDL and LDL in serum, with corresponding reduction of (p<0.001) serum-HDL. Ashvagandharishta also showed increased serum protein (p<0.05) and albumin (p<0.01) with decrease in bilirubin (p<0.01). Additionally, Ashvagandharishta administration revealed up-regulation in antioxidant genes such as CAT and GPx in liver with concomitant down-regulation in proinflammatory IL-6gene (p<0.01). Histopathological parameters revealed restoration of normal tissue architecture by both doses of Ashvagandharishta. CONCLUSIONS: Consortium of yeasts from Woodfordia fruticosa flowers showed better fermentation pattern for Ashvagandharishta produced with acceptable organoleptic properties. Hepatoprotection shown by Ashvagandharishta was mainly through prevention of oxidative damage. Up-regulation of CAT and GPx genes and corresponding down regulation of proinflammatory IL6 gene was revealed as possible mechanism of its action.

Beneficial effects of flaxseed oil and fish oil diet are through modulation of different hepatic genes involved in lipid metabolism in streptozotocin-nicotinamide induced diabetic rats.

Dietary omega-3 fatty acids have been demonstrated to have positive physiological effects on lipid metabolism, cardiovascular system and insulin resistance. Type-2 diabetes (T2DM) is known for perturbations in fatty acid metabolism leading to dyslipidemia. Our objective was to investigate beneficial effects of dietary flaxseed oil and fish oil in streptozotocin-nicotinamide induced diabetic rats. Thirty-six adult, male, Wistar rats were divided into six groups: three diabetic and three non-diabetic. Diabetes was induced by an injection of nicotinamide (110 mg/kg) and STZ (65 mg/kg). The animals received either control, flaxseed oil or fish oil (10 % w/w) enriched diets for 35 days. Both diets lowered serum triglycerides and very low-density lipoprotein cholesterol levels and elevated serum high-density lipoprotein cholesterol levels in diabetic rats, while serum total cholesterol and LDL-C levels remained unaffected. Both the diets increased omega-3 levels in plasma and RBCs of diabetic rats. Flaxseed oil diet significantly up-regulated the key transcription factor peroxisome proliferator-activated receptor-α (PPAR-α ) and down-regulated sterol regulatory element-binding protein-1 (SREBP-1) in diabetic rats, which would have increased ß-oxidation of fatty acids and concomitantly reduced lipogenesis respectively, thereby reducing TG levels. Fish oil diet, on the contrary lowered serum TG levels without altering PPAR-α while it showed a non-significant reduction in SREBP-1 expression in diabetic rats. Another key finding of the study is the activation of D5 and D6 desaturases in diabetic rats by flaxseed oil diet or fish oil diets, which may have resulted in an improved omega-3 status and comparable effects shown by both diets. The reduced expression of Liver-fatty acid binding protein in diabetic rats was restored by fish oil alone, while both diets showed equal effects on adipocyte fatty acid-binding protein expression. We also observed down-regulation of atherogenic cytokines tumor necrosis factor-α and interleukin-6 by both the diets. In conclusion, dietary flaxseed oil and fish oil have therapeutic potential in preventing lipid abnormalities in T2DM.

Dietary flaxseed oil and fish oil modulates expression of antioxidant and inflammatory genes with alleviation of protein glycation status and inflammation in liver of streptozotocin-nicotinamide induced diabetic rats.

Beneficial effects of dietary flaxseed oil or fish oil on streptozotocin-nicotinamide induced diabetic rats were investigated. Rats were divided into three diabetic and three non-diabetic groups and received control, flaxseed oil or fish oil diets (10%w/w). Both diets reduced blood glucose, TBARS and hepatic NO. The extent of glycation measured in terms of glycated albumin and hemoglobin was reduced significantly with both diets. Flaxseed oil diet up-regulated hepatic catalase (CAT) (activity and expression), superoxide dismutase (SOD) (activity and expression) and glutathione peroxidase (GPx) expression. Fish oil diet up-regulated hepatic CAT (activity and expression), paraoxonase-1 (PON-1) expression and down-regulated heme oxygenase-1 (HO-1) expression. Furthermore, both diets down-regulated the expression of hepatic inflammatory genes TNF-α, IL-6, MCP-1, INF-γ and NF-κB. These results were supported by histopathological observations which showed better tissue preservation in both the diets. Thus, both the diets proved to be beneficial in preventing tissue injury and alleviating diabetic insults in the livers of STZ-NIC diabetic rats.