Anti-Obesity Effect of Fish Oil and Fish Oil-Fenofibrate Combination in Female KK Mice

Abstract

Aim:The aim of our study is to elucidate the effects of EPA-or DHA-rich fish oil, and of the latter plus fenofibrate, on lipid metabolism in female KK mice. Methods: Female KK mice were fed purified experimental diets containing lard/safflower oil (4:6, Lard/SO), EPA-rich fish oil (EPA), DHA-rich fish oil (DHA), or DHA-rich fish oil plus 0.2% (w/w) fenofibrate (DHA FF) for 8 weeks. At the end of the experiments, we measured levels of plasma lipids, hepatic triglycerides, and cholesterol, as well as the hepatic mRNA expression of lipogenic and lipidolytic genes. Results: The final body weight of EPA-and DHA-fed groups was significantly lower than that of the Lard/SO-fed group, and that of the DHA FF-fed group was the lowest. All three fish oil treatments significantly reduced plasma insulin levels. Hepatic lipid levels significantly decreased in all three of these groups compared with the Lard/SO-fed group. Plasma adiponectin increased in both the EPAand DHA-fed groups, but the increase was suppressed in the DHA FF-fed group. Hepatocytes of Lard/SO-fed mice were filled with numerous fat droplets, but fat accumulation was inhibited in both EPA-and DHA-fed mice and was significantly prevented by fenofibrate treatment. SREBP-1c mRNA levels were decreased by about half in EPA-and DHA-fed mice compared with Lard/SO-fed mice. FAS, Insig-1, HMG-CoA reductase, and LDL-receptor mRNA levels also markedly decreased in both EPA-and DHA-fed mice, but there was no additional decrease in DHA FF fed mice. Fenofibrate treatment significantly induced mRNA expression of AOX and UCP-2, but not of PPAR . Conclusion: These data suggest that fish oil inhibited body weight gain and exhibited an anti-obesity effect through the inhibition of lipid synthesis in female KK mice. Furthermore, fenofibrate treatment markedly inhibited body weight gain by the induction of fatty acid oxidation. Plasma adiponectin levels did not increase in mice fed DHA-rich fish oil with fenofibrate, although white adipose tissue (WAT) weight significantly decreased. We considered that adiponectin sensitivity increased more in mice fed DHA-rich fish oil with fenofibrate than in mice fed DHA-rich fish oil alone.

The differential effects of EPA and DHA on cardiovascular risk factors

“…There is also growing evidence from animal studies that fish oil intake increases insulin sensitivity and adiponectin levels in insulin resistant rats and mice (187,188) . In contrast, intervention studies generally show little or no effect of fish oils on insulin sensitivity and glycaemic control in human subjects.…”

Docosahexaenoic Acid Content in Plasma Phospholipids and Desaturase Indices in Obese Children

“…Monounsaturated fatty acids (MUFA) are also associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension 7) . Furthermore, n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert hypolipidemic effects and prevent the development of obesity and insulin resistance in animals fed high-fat diets [8][9][10] ; however, the mechanisms of these series of fatty acids against obesity have not been fully elucidated. In regard to n-3 PUFAs, some mechanisms of the anti-obesity effect have been proposed in in vitro and in vivo studies: upregulation of mitochondrial biogenesis and increased beta-oxidation in adipocytes 11) , inhibition of adipocyte differentiation 12) , increase of fatty acid oxidation in the small intestine 13) , and marked stimulation of thermogenic activity in brown adipose tissue 14) .…”

Effects of Simultaneous Dietary Fish Oil Ingestion and Sulfur Amino Acid Supplementation on the Lipid Metabolism in Hepatoma-Bearing Rats with Hyperlipidemia

“…Fatty acid oxidation was estimated using liver slices ( 30 ). Liver slices weighing 200 mg were placed in 2 mL of Krebs-Ringer phosphate buffer (pH ϭ 7.4) containing 37 kBq/ mol/assay of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitic acid (original specific radioactivity ϭ 310 MBq/mmol, NEN Research Products). Each tube was gassed with 100% O 2 , connected with a rubber tube (18 mm in inside diameter) to a counting vial which held circular filter paper (No.…”

“…Dietary fish oil, which is rich in n -3 polyunsaturated fatty acids, is well known to suppress concentrations of serum lipids such as triglyceride, cholesterol, phospholipid and nonesterified fatty acid (NEFA) in normal rats ( 8 , 9 ), rats with cancer-related hyperlipidemia ( 10 ), non-insulin dependent diabetes mellitus mice ( 11 ), and hyperlipidemic patients ( 12 ). Dietary supplementation of amino acids and their derivatives have been demonstrated to affect the lipid metabolism.…”