Opposing Effects of Omega-3 and Omega-6 Long Chain Polyunsaturated Fatty Acids on the Expression of Lipogenic Genes in Omental and Retroperitoneal Adipose Depots in the Rat

Mühlhäusler, B. S.; Cook-Johnson, Rebecca J.; James, Michael J.; Miljkovic, Dijana; Duthoit, Emmanuelle; Gibson, Robert A.

doi:10.1155/2010/927836

Cited by 58 publications

(57 citation statements)

References 22 publications

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“…To the best of our knowledge, our results show for first time in humans the modulatory effect of n-3 PUFA in reducing the expression of lipogenic genes in AT, which has been described previously in studies with animal models (Ikeda et al 1998;Muhlhausler et al 2010).…”

Section: Discussionsupporting

confidence: 81%

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

et al. 2014

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Adipose tissue (AT) is a key organ in the regulation of total body lipid homeostasis, which is responsible for the storage and release of fatty acids according to metabolic needs. We aimed to investigate the effect of the quantity and quality of dietary fat on the lipogenesis and lipolysis processes in the AT of metabolic syndrome (MetS) patients. A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to one of four diets: (a) high-saturated fatty acid (HSFA) (b) highmonounsaturated fatty acid, and (c, d) two low-fat, highcomplex carbohydrate diets supplemented with long chain (LC) n-3 (LFHCC n-3) polyunsaturated fatty acids (PUFA) or placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the same fatty acid composition as the original diets was conducted post-intervention. Long-term consumption of the LFHCC diet induced an increase in the fasting expression levels of the sterol regulatory element binding protein-1 and stearoyl-CoA desaturase D9-desaturase genes, whereas the supplementation of this diet with n-3 PUFA reversed this effect (p = 0.007). In contrast, long-term consumption of the HSFA diet increased the expression of the adipose triglyceride lipase (ATGL) gene, at both fasting and postprandial states (both, p \ 0.001). Our results showed the anti-lipogenic effect exerted by LC n-3 PUFA when administered together with a LFHCC diet. Conversely, a diet high in saturated fat increased the expression of the lipolytic gene ATGL relative to the other diets.

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Section: Discussionsupporting

confidence: 81%

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

et al. 2014

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“…As shown in Table 3, the level of phosphorylated ACC was increased in the high n-3:n-6 group, consistent with decreased activity of the enzyme and reduced lipid biosynthesis. Similarly, levels of FASN, HMGCR, and SREBP-1 were reduced, effects consistent with both PPAR activation and reduced mTOR activity (44)(45)(46)(47)(48)(49)(50). Strikingly, the unbiased ranking of effects reported in Fig.…”

Section: Discussionmentioning

confidence: 55%

Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids

et al. 2012

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An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to inhibit the development of mammary cancer in animal models. However, the molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown. Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty acids on cell signaling in a rat model of chemically induced mammary carcinoma. Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6 treatment group compared with the low n-3:n-6 treatment group. These changes were associated with decreased cyclin-D1 and phospho-retinoblastoma protein expression and increased levels of cyclin-dependent kinase inhibitors, CIP1 (p21) and KIP1 (p27). In addition, the apoptotic index was increased in carcinomas from the high n-3:n-6 group and was associated with elevated apoptotic protease-activating factor 1 and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein expression were consistent with reduced inflammation and suppressed mTOR activity, and the molecular signature associated with high n-3:n-6 treatment revealed changes in PPARg activation and suppression of lipid synthesis. Together, our findings indicate that the molecular effects of high dietary n-3 to n-6 ratios are heterogeneous in nature but point to consistent changes in lipid metabolism pathways, which may serve as potential therapeutic targets for cancer prevention and control. This study identifies the pathways modulated by dietary fatty acid ratios in a rat model of breast cancer, with implications for cancer prevention. Cancer Res; 72(15); 3795-806. Ó2012 AACR.

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“…One proposed mechanism is based on differences in the relative tissue amounts of arachidonic acid and EPA, because arachidonic acid has been shown in vitro (24) and in rodents (1) to promote adipose tissue development. It should be noted that n-6 PUFA have been proposed to be prolipogenic (25), and the observed trends could thus be speculated to be driven by an increased fat deposition in the SO group. However, we find that both oil supplements are positively related to s.c. fat deposition, which could imply that the parents did not completely compensate the intake of intervention oils in the habitual fat intake of their infants.…”

Section: Discussionmentioning

confidence: 96%

A Randomized Controlled Intervention With Fish Oil Versus Sunflower Oil From 9 to 18 Months of Age: Exploring Changes in Growth and Skinfold Thicknesses

et al. 2011

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n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), from fish oil (FO), in rodents have been shown to reduce adipogenesis. Evidence of an effect on adipose tissue mass in humans is limited, and no studies have specifically aimed to elucidate this in infancy. To explore whether n-3 LCPUFA intake affects adipose tissue growth, we randomly allocated 154 healthy infants to daily supplementation with FO or sunflower oil (SO) from 9 to 18 mo of age and measured z-score changes in various anthropometric assessments of body size and skinfold thicknesses and plasma adipokine concentrations. Among the 133 completing infants, erythrocyte n-3 PUFA increased more in those receiving FO than in infants receiving SO [12.2 Ϯ 0.7 (mean Ϯ SE) versus 2.0 Ϯ 0.4 fatty acid percentage (FA%), p Ͻ 0.001] with a concomitant larger decrease in n-6 PUFA (Ϫ8.9 Ϯ 0.7 versus Ϫ0.9 Ϯ 0.6 FA%, p Ͻ 0.001). We found no association between FO consumption relative to SO consumption and any of the anthropometric measures related to the size of the fat mass, but infants in the FO group had a lower skinfold ratio (triceps/ subscapular) at 18 mo than those in SO group (p ϭ 0.02). Our findings do not support the hypothesis that dietary n-3 LCPUFA is important for infant fat mass, but future studies testing this specifically are warranted. A sedentary lifestyle that favors a positive energy balance is generally acknowledged as the major cause of the increasing prevalence of obesity, but other potential contributing factors are also receiving attention. Among these are the dietary changes in the consumption of polyunsaturated fatty acids (PUFA) toward a higher n-6 and lower n-3 PUFA intake, which has been suggested as a partial explanatory factor (1). Dietary n-3 long-chain PUFA (LCPUFA) in rodents has been shown to prevent diet-induced obesity (2) and has also been reported to enhance fat mass reduction in two randomized weight-loss trials in overweight adults (3) and obese women with type-2 diabetes (4).Early life is a period of rapid growth with major changes in both body size and composition. It is well established that docosahexaenoic acid (DHA, 22:6n-3) is important for, e.g., visual development in infancy (5), but it is presently unknown to what extent n-3 LCPUFA should be considered relevant with respect to adiposity. The natural content of n-3 PUFA in breast milk has been found to be positively associated with infant weight gain in preterm (6) but not term-born infants (7). Furthermore, two intervention studies giving n-3 LCPUFA to pregnant and/or lactating mothers suggest a programming effect on later infant BMI, although in opposite directions (8,9). However, no studies have to our knowledge aimed specifically to investigate whether dietary n-3 LCPUFA in early life is associated with the size of the fat mass per se.Inspired by the clear finding in rodents, this study was conducted to attempt to elucidate whether growth and fat deposition in healthy Danish infants during the complementary feeding period, 9 -18 mo of age, are associ...

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Opposing Effects of Omega-3 and Omega-6 Long Chain Polyunsaturated Fatty Acids on the Expression of Lipogenic Genes in Omental and Retroperitoneal Adipose Depots in the Rat

Cited by 58 publications

References 22 publications

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids

A Randomized Controlled Intervention With Fish Oil Versus Sunflower Oil From 9 to 18 Months of Age: Exploring Changes in Growth and Skinfold Thicknesses

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