omacor and Metabolic-Syndrome

Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides. This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of ω-3 fatty acids on adipocytes and macrophages in vitro. Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks. Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged. The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment. Adipose and muscle ω-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin. In vitro, M1-polarized macrophages expressed high levels of MCP-1. The addition of ω-3 fatty acids reduced MCP-1 expression with no effect on TNF-α. In addition, ω-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages. Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity.

Topics: Abdominal Fat; Angiogenesis Inducing Agents; Anti-Inflammatory Agents, Non-Steroidal; Body Mass Index; Capillaries; Cells, Cultured; Chemokine CCL2; Coculture Techniques; Dietary Supplements; Docosahexaenoic Acids; Down-Regulation; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Insulin Resistance; Macrophages; Male; Metabolic Syndrome; Middle Aged; Muscles; Obesity; RNA, Messenger

Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and type 2 diabetes. This study measured responses to testosterone deficiency in high-carbohydrate, high-fat (H) diet-fed rats. We then tested whether eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ethyl esters (Omacor) reversed these metabolic changes. Male Wistar rats (8⁻9 weeks old) were divided into eight groups with four groups fed corn starch and four groups fed H diet. For each diet, one group received diet only; one group was orchidectomized; one group was given leuprolide (gonadotrophin-releasing hormone agonist, 2 mg/kg every 4th week); and the last group was treated with leuprolide and their diet was supplemented with 3% Omacor for the last eight weeks. The protocol was for 16 weeks. Leuprolide worsened metabolic syndrome symptoms and cardiovascular function, and orchidectomy produced greater responses. In H fed leuprolide-treated rats, Omacor decreased systolic blood pressure and left ventricular diastolic stiffness, reduced infiltration of inflammatory cells and collagen deposition in the heart, and reduced lipid accumulation and inflammatory cell infiltration without improving liver damage. These results suggest that Omacor has potential to attenuate metabolic complications in prostate cancer patients with induced testosterone deprivation.

Topics: Animals; Antineoplastic Agents, Hormonal; Blood Pressure; Diet, Carbohydrate Loading; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Humans; Leuprolide; Liver; Male; Metabolic Syndrome; Prostatic Neoplasms; Rats; Rats, Wistar; Testosterone

Topics: Animals; Anticholesteremic Agents; Atorvastatin; Dietary Fats; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Food-Drug Interactions; Gene Expression Regulation; Hypercholesterolemia; Male; Metabolic Syndrome; Rats; Rats, Inbred Strains

Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cerebral Cortex; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Hippocampus; Lipid Peroxides; Male; Maze Learning; Memory; Metabolic Syndrome; Rats; Rats, Inbred SHR

Topics: Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Humans; Hypertriglyceridemia; Life Style; Metabolic Syndrome