docosapentaenoic-acid and Obesity

To evaluate the influence of ω-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on body composition, insulin resistance, and lipemia of women with type 2 diabetes, the authors evaluated 41 women (60.64 ± 7.82 years) with high blood pressure and diabetes mellitus in a randomized and single-blind longitudinal intervention study. The women were divided into 3 groups: GA (2.5 g/d fish oil), GB (1.5 g/d fish oil), and GC (control). The capsules with the supplement contained 21.9% of eicosapentaenoic acid and 14.1% of docosapentaenoic acid. Biochemical (glucose, glycated hemoglobin, total and fractional cholesterol, triglycerides, and insulin) and anthropometric (body mass, stature, waist circumference [WC], and body composition) evaluations were performed before and after the 30 days of intervention. Homeostasis model assessment-insulin resistance and the Quantitative Insulin Sensitivity Check Index were used to evaluate the insulin resistance and insulin sensitivity (IS), respectively. GB presented a greater loss of body mass and WC (P < .05), greater frequency of glycemic and total cholesterol reduction, and an increase of high-density lipoprotein cholesterol compared with GA. Thus, a high dose of ω-3 PUFA can reduce IS. A lower dose of ω-3 PUFA positively influenced body composition and lipid metabolism.

Topics: Aged; Blood Glucose; Body Composition; Body Mass Index; Cholesterol; Diabetes Mellitus, Type 2; Dietary Supplements; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Fish Oils; Glycated Hemoglobin; Humans; Hyperlipidemias; Insulin; Insulin Resistance; Middle Aged; Obesity; Single-Blind Method; Triglycerides; Waist Circumference

Many studies have investigated the beneficial effects of n-3 polyunsaturated fatty acids, such as their potential for lowering lipid levels and reducing diabetes risk. However, few studies have specifically examined docosapentaenoic acid (DPA), an n-3 polyunsaturated fatty acid with limited availability in its pure form. We hypothesized that DPA would have lipid-lowering effects and improve insulin resistance in KK/Ta mice. To test our hypothesis, 7-week-old KK/Ta mice were fed a high-fat diet for 12 weeks to induce obesity before being divided into 3 groups and fed an experimental diet for 10 weeks. The experimental diets were: LSO, using lard and safflower oil as fat sources; SO, in which lard in the LSO diet was replaced with safflower oil; and DPA, in which lard in the LSO diet was replaced with DPA oil. After 10 weeks, plasma triglyceride and total cholesterol concentrations were significantly decreased in the DPA group, but not in the SO group. Sterol regulatory element-binding protein-1 and stearoyl-CoA desaturase-1 gene expressions involved in fatty acid synthesis in the liver were significantly lower in the DPA group compared with the LSO group. Plasma glucose concentrations were significantly decreased in both the SO group and the DPA group compared with the LSO group, whereas plasma insulin concentrations were significantly decreased in the DPA group alone. These results indicate that DPA has plasma lipid-lowering and hypoglycemic effects, possibly from suppression of fatty acid synthesis in the liver.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Lipid Metabolism; Liver; Mice; Obesity; Safflower Oil

7S,15R-Dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) and 7S,15R,16S,17S-tetrahydroxy-docosapentaenoic acid (TH-DPA) are two novel lipid mediators derived from docosahexaenoic acid (DHA) that we previously synthesized via combined enzymatic and chemical reactions. In the present study, we investigated the effects of these compounds on disturbances in lipid metabolism and liver inflammation induced by a high fat diet (HFD) in mice. Male BALB/c mice were randomly divided into four groups (n = 10/group): controls, HFD only, HFD + diHEP-DPA, and HFD + TH-DPA. Mice in HFD + diHEP-DPA and HFD + TH-DPA groups were orally administered 20 μg/kg of diHEP-DPA or TH-DPA, respectively. Measurements of adipose accumulation and liver inflammation showed that both diHEP-DPA and TH-DPA decreased adipose tissue mass and liver color depth, as well as total cholesterol, triglycerides, and low-density lipoprotein-cholesterol in the serum of HFD-fed mice compared with mice in the HFD-only group, while elevating high-density lipoprotein-cholesterol. Both of them also decreased hepatic expression of genes encoding lipid synthesis-related proteins (PPARγ, SIRT1, SREBP-1c and FASN) and increased the expression of genes encoding proteins involved in lipid degradation (PPARα and CPT-1) in the liver. Western blotting and quantitative RT-PCR confirmed that diHEP-DPA or TH-DPA administration modulated the expression of inflammation-related genes (TNF-α and IL-6) and inhibited activation of the NF-κB signaling pathway in livers of HFD-fed mice. Taken together, our data indicate that diHEP-DPA and TH-DPA ameliorate liver inflammation and inhibit HFD-induced obesity in mice.

Topics: Adipose Tissue; Animals; Cholesterol; Diet, High-Fat; Docosahexaenoic Acids; Fatty Acids, Unsaturated; Inflammation; Lipid Metabolism; Lipogenesis; Lipoxygenase; Liver; Male; Mice; Mice, Inbred BALB C; Obesity; Triglycerides

The aim of the present study was to assess and compare the effects of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) supplementation on lipid metabolism in 4 month-old male C57BL/6J mice fed a high-fat diet. The high-fat fed mice showed evidence of fatty liver, obesity and insulin resistance after being on the high-fat diet for 6 weeks compared with the control low-fat diet fed mice. Supplementation of the high-fat diet with either EPA, DPA or DHA prevented the fatty liver, prevented high serum cholesterol and serum glucose and prevented high liver cholesterol levels. DPA (but not EPA or DHA) was associated with a significantly improved homeostasis model assessment of insulin resistance (HOMA-IR) compared with the high-fat fed mice. Supplementation with DPA and DHA both prevented the decreased serum adiponectin levels, compared with EPA and the high-fat diet. In addition, supplementation with DPA and DHA both prevented the increased serum alanine aminotransferase (ALT) levels compared with EPA and the high-fat group, which can be attributed to down-regulation of TLR-4/NF-κB signaling pathway and decreasing lipogenesis in the liver. Therefore, DPA and DHA seem to exert similar effects in cardio-metabolic protection against the high-fat diet and these effects seem to be different to those of EPA.

Topics: Animals; Blood Glucose; Cholesterol; Diet, High-Fat; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Fatty Liver; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity

Non-alcoholic fatty liver disease (NAFLD) given its association with obesity and diabetes may perhaps exert distinct free fatty acids (FFA) pattern, but the understanding of this phenomenon is limited. To this effect, we evaluated FFA profiles among healthy subjects and NAFLD patients stratified by body weight, to identify FFA valuable for early diagnosis of NAFLD.. Serum FFA profiles of healthy and NAFLD (lean, overweight and obese) subjects was determined using gas chromatography-mass spectrometry (GC-MS) and distinctions in FFA patterns were evaluated using one-way ANOVA while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFA significant for diagnosing NAFLD.. NAFLD patients presented significantly higher (P < 0.05) serum FFA profiles compared to healthy controls (HC). While total FFA profiles were insignificantly different between lean (2093.33 ± 558.11 μg/ml) and overweight (2420.81 ± 555.18 μg/ml) NAFLD patients, obese NAFLD (2739.01 ± 810.35 μg/ml) presented most significantly elevated (P < 0.05) total FFA profiles compared with HC. Of the four FFA; myristic acid (14:0), palmitoleic acid (16:1), γ-linolenic acid (γ-18:3) and cis-7,10,13,16,19-docosapentaenoic acid (22:5), selected in ROC analysis given their high Youden's index and AUC, only 14:0; 5.58(1.37, 22.76) and 16:1; 4.36(1.34, 14.13) had statistical significant odd ratios.. Our findings suggest 14:0 and 16:1 are promising for early diagnosis of NAFLD.

Topics: Adult; Body Mass Index; Case-Control Studies; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Myristic Acid; Non-alcoholic Fatty Liver Disease; Obesity; Overweight; Thinness

Considerable research has focused upon the role of linoleic acid (LNA; 18:2n-6) as a competitive inhibitor of α-linolenic (ALA; 18:3n-3) metabolism; however, little data exist as to the impact of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) on ALA metabolism. We tested the hypothesis that a high SFA diet, compared to a high MUFA (oleic acid 18:1n-9) diet, reduces ALA conversion to long chain n-3 fatty acids. Mice were fed for 12 weeks on three diets: (1) a control, 16 % fat energy diet consisting of similar levels of SFA and MUFA (2) a 50 % fat energy high MUFA energy diet (35 % MUFA and 7 % SFA) or (3) a 50 % fat energy, high SFA energy diet (34 % SFA, 8 % MUFA). ALA and LNA content remained constant. Analysis of hepatic lipids demonstrated a selective reduction (40 %) in ALA but not LNA and a 35 % reduction in eicosapentaenoic acid (EPA; 20:5n-3) in the high MUFA mice compared to the other groups. Lower content of ALA was reflected in the neutral lipid fraction, while smaller levels of phospholipid esterified EPA and docosapentaenoic acid (DPA; 22:5n-3) were evident. Docosahexaenoic acid (DHA; 22:6n-3) content was elevated by the high SFA diet. Expression of Fads1 (Δ5 desaturase) and Fads2 (Δ6 desaturase) was elevated by the high MUFA and reduced by the high SFA diet. These data indicate that a high MUFA diet, but not a high SFA diet, reduces ALA metabolism and point to selective hepatic disposition of ALA versus LNA.

Topics: alpha-Linolenic Acid; Animals; Delta-5 Fatty Acid Desaturase; Diet, High-Fat; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Oleic Acids