Maternal omega-3 fatty acid deficiency affects fetal thermogenic development and postnatal musculoskeletal growth in mice.

Maternal omega-3 (n-3) polyunsaturated fatty acids (PUFAs) deficiency can affect offspring's adiposity and metabolism by modulating lipid and glucose metabolism. However, the impact of n-3 PUFA deficiency on the development of fetal thermogenesis and its consequences is not reported. Using an n-3 PUFA deficient mice, we assessed fetal interscapular brown adipose tissue (iBAT), body fat composition, insulin growth factor-1 (IGF-1), glucose transporters (GLUTs), and expression of lipid storage & metabolic proteins in the offspring. The n-3 PUFA deficiency did not change the pups' calorie intake, organ weight, and body weight. However, the offspring's skeletal growth was altered due to excess fat to lean mass, reduced tibia & femur elongation, dysregulated IGF-1 in the mother and pups (P< .05). Localization of uncoupling protein 1 (UCP1) in iBAT exhibited a reduced expression in the deficient fetus. Further, UCP1, GLUT1, GPR120 were downregulated while FABP3, ADRP, GLUT4 expressions were upregulated in the BAT of the deficient offspring (P< .05). The deficiency decreased endogenous conversion of the n-3 LCPUFAs from their precursors and upregulated SCD1, FASN, and MFSD2A mRNAs in the liver (P< .05). An altered musculoskeletal growth in the offspring is associated with impaired browning of the fetal adipose, dysregulated thermogenesis, growth hormone, and expression of glucose and fatty acid metabolic mediators due to maternal n-3 PUFA deficiency. BAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency. Maternal n-3 PUFA intake may prevent excess adiposity by modulating fetal development of thermogenesis and skeletal growth dynamics in the mice offspring.

Diets with low n-6:n-3 PUFA ratio protects rats from fructose-induced dyslipidemia and associated hepatic changes: Comparison between 18:3 n-3 and long-chain n-3 PUFA.

In the present study, we investigated the impact of substituting alpha-linolenic acid (ALA) or long-chain n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) for linoleic acid and hence decreasing n-6:n-3 PUFA ratio on high-fructose diet-induced hypertriglyceridemia and associated hepatic changes. Weanling male Wistar rats were divided into four groups and fed with starch-diet (n-6:n-3 PUFA ratio 215:1) and high-fructose diets with different n-6:n-3 PUFA ratio (215:1, 2:1 with ALA and 5:1 with long-chain n-3 PUFA) for twenty-four weeks. Substitution of linoleic acid with ALA (n-6:n-3 PUFA ratio of 2) or long-chain n-3 PUFA (n-6:n-3 PUFA ratio of 5) protected the rats from fructose-induced dyslipidemia, hepatic oxidative stress and corrected lipogenic and proinflammatory gene expression. Both ALA and long-chain n-3 PUFA supplementation also reversed the fructose-induced upregulation of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) gene, which is involved in the generation of active glucocorticoids in tissues. Although both ALA and LC n-3 PUFA prevented fructose-induced dyslipidemia to a similar extent, compared to ALA, LC n-3 PUFA is more effective in preventing hepatic oxidative stress and inflammation.

Substitution of linoleic acid with α-linolenic acid or long chain n-3 polyunsaturated fatty acid prevents Western diet induced nonalcoholic steatohepatitis.

Imbalance in the n-6 polyunsaturated fatty acids (PUFA) and n-3 PUFA in the Western diet may increase the risk of nonalcoholic fatty liver disease (NAFLD). This study investigates the impact of substitution of linoleic acid with α-linolenic acid (ALA) or long chain (LC) n-3 PUFA and hence decreasing n-6:n-3 fatty acid ratio on high fat, high fructose (HFHF) diet induced nonalcoholic steatohepatitis (NASH). Male Sprague-Dawley rats were divided into four groups and fed control diet, HFHF diet (n-6:n-3 ratio of 200), HFHF diet with ALA (n-6:n-3 ratio of 2) or HFHF diet with LC n-3 PUFA (n-6:n-3 ratio of 5) for 24 weeks. Rats fed HFHF diet with n-6:n-3 ratio of 200 resulted in hepatic steatosis, induced glucose intolerance, insulin resistance and oxidative stress accompanied by increase in markers of inflammation, plasma lipids and aminotransferase levels. Histopathological examination of liver further confirmed the establishment of NASH. ALA and LC n-3 PUFA supplementation prevented hepatic steatosis and dyslipidemia by inhibiting lipogenesis and increasing insulin sensitivity. Furthermore, n-3 PUFA supplementation attenuated hepatic oxidative stress by restoring antioxidant status, decreased inflammation and preserved hepatic architecture. These finding suggest that decreasing n-6:n-3 ratio prevented HFHF induced NASH by attenuating oxidative stress and inflammation.

Partial replacement of dietary linoleic acid with long chain n-3 polyunsaturated fatty acids protects against dextran sulfate sodium-induced colitis in rats.

Imbalances in the dietary n-6 and n-3 polyunsaturated fatty acids have been implicated in the increased prevalence of inflammatory bowel disease. This study investigated the effects of substitution of linoleic acid with long chain n-3 polyunsaturated fatty acids and hence decreasing n-6:n-3 fatty acid ratio on inflammatory response in dextran sulfate sodium induced colitis. Male weanling Sprague Dawley rats were fed diets with n-6:n-3 fatty acid in the ratios of 215,50,10 or 5 for 3 months and colitis was induced by administration of dextran sulfate sodium in drinking water during last 11 days. Decreasing the dietary n-6:n-3 fatty acid ratio to 10 and 5 significantly attenuated the severity of colitis as evidenced by improvements in clinical symptoms, reversal of shortening of colon length, reduced severity of anemia, preservation of colonic architecture as well as reduced colonic mucosal myeloperoxidase activity. This protection was associated with suppression of colonic mucosal proinflammatory mediators such as TNFα, IL-1ß and nitric oxide. These findings suggest that long chain n-3 polyunsaturated fatty acids at a level of 3.0 g/kg diet (n-6:n-3 ratio of 10) prevents dextran sulfate sodium induced colitis by suppressing the proinflammatory mediators.

Attenuation of colonic inflammation by partial replacement of dietary linoleic acid with α-linolenic acid in a rat model of inflammatory bowel disease.

Increasing prevalence of inflammatory bowel disease may be due to imbalance in the intake of n-6 and n-3 PUFA in the diet. This study investigates the impact of varying ratios of dietary linoleic acid (LA, 18 : 2n-6) to α-linolenic acid (ALA, 18 : 3n-3) on the inflammatory response in dextran sulphate sodium (DSS)-induced colitis. Weanling male Sprague-Dawley rats were divided into five groups: a non-colitic group with a LA:ALA ratio of 215 (CON-215), and colitic groups with LA:ALA ratios of 215 (DSS-215), 50 (DSS-50), 10 (DSS-10) and 2 (DSS-2). Blends of groundnut, palmolein and linseed oils were used to provide varying LA:ALA ratios. All the rats were fed the respective experimental isoenergetic diets containing 10 % fat for 90 d and DSS was administered during the last 11 d. Colonic inflammation was evaluated by clinical, biochemical and histological parameters. The results showed attenuation of colitis in the DSS-2 group as evidenced by significant reductions in disease activity index, mucosal myeloperoxidase activity (P < 0·05), alkaline phosphatase activity (P < 0·01) and increase in colon length (P < 0·01) compared to the groups fed with higher ratios (DSS-215). This was accompanied by significant reductions in mucosal proinflammatory cytokines TNF-α (P < 0·01) and IL-1ß (P < 0·01) and improvement in the histological score. Further, ALA supplementation increased long-chain (LC) n-3 PUFA and decreased LC n-6 PUFA in colon structural lipids. These data suggest that substitution of one-third of LA with ALA (LA:ALA ratio 2) mitigates experimental colitis by down-regulating proinflammatory mediators.

Dietary (n-3) long chain polyunsaturated fatty acids prevent sucrose-induced insulin resistance in rats.

This study was designed to determine the effect of substituting (n-3) long-chain PUFAs (LCPUFAs) for linoleic acid and hence decreasing the (n-6):(n-3) fatty acid ratio on sucrose-induced insulin resistance in rats. Weanling male Wistar rats were fed casein-based diets containing 100 g/kg fat for 12 wk. Insulin resistance was induced by replacing starch (ST) with sucrose (SU). The dietary fats were formulated with groundnut oil, palmolein, and fish oil to provide the following ratios of (n-6):(n-3) fatty acids: 210 (ST-210, SU-210), 50 (SU-50), 10 (SU-10), and 5 (SU-5). Compared with starch (ST-210), sucrose feeding (SU-210) significantly increased the plasma insulin and triglyceride concentrations and the plasma insulin area under the curve (AUC) in response to an oral glucose load. Adipocytes isolated from rats fed SU-210 had greater lipolytic rate, lower insulin stimulated glucose transport, and lower insulin-mediated antilipolysis than those from rats fed ST-210. Decreasing the dietary (n-6):(n-3) ratio in sucrose-fed rats (SU-10 and SU-5) normalized the plasma insulin concentration and the AUC of insulin after a glucose load. The sucrose-induced increase in plasma triglyceride concentration was normalized in rats fed SU-50, SU-10 and SU-5. Further, sucrose-induced alterations in adipocyte lipolysis and antilipolysis were partially reversed and glucose transport improved in rats fed diets SU-5 and SU-10. In diaphragm phospholipids, decreasing the (n-6):(n-3) ratio in the diet increased the concentration of (n-3) LCPUFAs with concomitant decreases in the concentration of (n-6) LCPUFAs. These results suggest that (n-3) LCPUFAs at a level of 2.6 g/kg diet [0.56% energy (n-3) LCPUFAs, (n-6):(n-3) ratio = 10] may prevent sucrose-induced insulin resistance by improving peripheral insulin sensitivity.

Dietary trans fatty acids alter diaphragm phospholipid fatty acid composition, triacylglycerol content and glucose transport in rats.

The present study evaluates the effect of dietary trans fatty acids on diaphragm phospholipid fatty acid composition, intramyocellular triacylglycerol content and insulin-stimulated glucose uptake in comparison with dietary saturated fatty acids. Male weanling WNIN rats were divided into three groups and fed for 3 months on one of the following diets containing 10 % oil differing in fatty acid composition: control diet, saturated fatty acid diet and trans fatty acid diet. Dietary trans fatty acids increased the intramyocellular triacylglycerols and decreased the ratio of 20 : 4n-6 to 18 : 2n-6 and long-chain PUFA levels (20 %) in diaphragm phospholipids, indicating inhibition of PUFA biosynthesis. However, saturated fatty acids decreased both 18 : 2n-6 and 20 : 4n-6 without change in the ratio. Trans fatty acid-induced alterations in diaphragm phospholipid fatty acid composition and intramyocellular triacylglycerol content were associated with decreased insulin-stimulated glucose transport in the diaphragm. These observations suggest that dietary trans fatty acids decrease diaphragm insulin sensitivity, possibly due to increased intramyocellular triacylglycerol accumulation and decreased long-chain PUFA in phospholipids.

Dietary trans-fatty acids alter adipocyte plasma membrane fatty acid composition and insulin sensitivity in rats.

The present study was designed to investigate the effects of dietary trans-fatty acids (TFA) present in Indian vanaspati (partially hydrogenated vegetable oils) in comparison with saturated fatty acids (SFA) on adipocyte plasma membrane fatty acid composition, fluidity, and insulin action. The effects of 3% energy (% en) TFA was studied at 2% and 4% en of linoleic acid (18:2 n-6). WNIN male weanling rats were divided into 4 groups and fed casein-based diet containing 10% groundnut oil control (CON), palmolein (SFA), blend of vanaspati and safflower oil (3% en TFA and 2% en 18:2 n-6, TFA-1), or blend of vanaspati and safflower oil (3% en TFA and 4% en 18:2 n-6, TFA-2) for 12 weeks. Compared with CON, rats fed TFA and SFA diets had high levels of fasting plasma insulin and triglycerides. Both TFA- and SFA-fed groups had low levels of arachidonic acid (20:4 n-6) in adipocyte plasma membrane phospholipids. However, adipocyte plasma membrane fluidity decreased only in TFA-fed rats. Norepinephrine-stimulated lipolysis was high, whereas the antilipolytic effect of insulin and insulin-stimulated glucose transport were low in the adipocytes of SFA- and TFA-fed rats. However, the extent of decrease in the antilipolytic effect of insulin and insulin-stimulated glucose transport was greater in TFA-fed rats. These findings suggest that diet providing approximately 10% en SFA (PUFA/SFA [P/S] ratio 0.2) decreased adipocyte insulin sensitivity in rats. In these diets, replacement of approximately 2% en SFA (16:0) and approximately 1% en monounsaturated fatty acid (18:1 cis) with TFA decreased adipocyte insulin sensitivity to a greater extent. However, increasing dietary 18:2 n-6 did not prevent or reduce the TFA-induced adipocyte insulin resistance.