Madhuri Vemuri

Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Prevents Trans-10, Cis-12 Conjugated Linoleic Acid (CLA)–Induced Insulin Resistance in Mice

BACKGROUND The objective of this study was to investigate if eicosapentaenoic acid (20:5n-3, EPA) or docosahexaenoic acid (22:6n-3, DHA) or both would prevent conjugated linoleic acid (CLA)-induced insulin resistance and fatty liver. METHODS Eight-week-old, pathogen-free C57BL/6N female mice (10 per group) were fed either a control diet or diets containing t10, c12-CLA (0.5 wt %), CLA + DHA (0.5% + 1.5 wt %), or CLA + EPA (0.5% + 1.5 wt %) for 8 weeks prior to sacrifice and tissue collection. RESULTS CLA supplementation caused an 8.9-fold increase in circulating insulin, a 2.6-fold increase in liver weight, and a 6.2-fold increase in the weight of total lipids in the liver as compared with the corresponding values in the control group. DHA prevented the CLA-induced insulin resistance, while EPA was ineffective. Both EPA and DHA prevented CLA-induced fatty liver and reduced weights of total liver lipids to the levels of the control group. CLA also reduced the plasma leptin and adiponectin concentrations to approximately 15% of those in the control group. Both EPA and DHA partially restored the CLA-induced decrease in leptin, but only DHA partially restored the plasma adiponectin. CONCLUSIONS Our results suggest that DHA but not EPA in fish oils may reduce insulin resistance which may be mediated through an increase in circulating adiponectin. These findings may have clinical implications in the dietary management of patients at risk of insulin resistance and diabetes.

Flaxseed oil prevents trans -10, cis -12-conjugated linoleic acid-induced insulin resistance in mice

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men

Our previous study with docosahexaenoic acid (DHA) supplementation to hypertriglyceridemic men showed that DHA reduced several risk factors for cardiovascular disease, including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we performed Affymetrix GeneChip microarray analysis of blood cells [treated with lipopolysaccharide (LPS) or vehicle] drawn before and after the supplementation of DHA from the hypertriglyceridemic men who participated in that study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then verified by quantitative real-time polymerase chain reaction (qRT-PCR). Both microarray and qRT-PCR data showed that DHA supplementation significantly suppressed the expression of low-density lipoprotein (LDL) receptor and cathepsin L1, both of which were also up-regulated by LPS. DHA supplementation also suppressed oxidized LDL (lectin-like) receptor 1 (OLR1). However, LPS did not induce OLR1 mRNA expression. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immunity, host defense and inflammatory responses were inversely regulated by LPS and DHA. These results provide supporting evidence for the anti-inflammatory effects of DHA supplementation, and reveal previously unrecognized genes that are regulated by DHA and are associated with risk factors of cardiovascular diseases.

Health Effects of Foods Rich in Polyphenols

We have reviewed literature regarding the health benefits of foods rich in phenolic compounds. Numerous epidemiological studies indicate an inverse association between fruit and vegetable intake and the risk for cardiovascular disease (CVD), ischemic stroke, and other chronic diseases. Besides providing essential vitamins, minerals, and dietary fiber, fruits contain polyphenols that exhibit antioxidant, antiinflammatory, and lipid lowering properties. Several types of berries, cherries, black grapes, and tea are rich sources of dietary phenolic compounds. There are a number of in vitro studies that demonstrate that these compounds reduce oxidative stress and inflammatory response. Data from human feeding studies are limited and inconsistent. Regardless of the inconsistencies, results from human intervention studies do show reduction in oxidative stress, markers of inflammation, serum triglycerides and low-density lipoproteincholesterol when the diets were supplemented with fruits or fruit extracts rich in polyphenols. The inconsistencies may be due to the differences in the amount and type of the polyphenols consumed, duration of supplementation, basal diet and health status of the subjects.