BackgroundDifferent healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome.MethodsWe conducted a randomized dietary study lasting for 18–24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m−2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids.ResultsBody weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (−0.18, mmol L−1 95% CI −0.35; −0.01, P = 0.04), LDL to HDL cholesterol (−0.15, −0.28; −0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (−0.04, −0.07; −0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference −84, −133; −37 ng L−1, P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, −0.23, −0.41; −0.05, P = 0.012) were associated with IL-1 Ra.ConclusionsHealthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.Electronic supplementary materialThe online version of this article (doi:10.1007/s11745-010-3490-4) contains supplementary material, which is available to authorized users.

The pivotal role of liver X receptors (LXRs) in the metabolic conversion of cholesterol to bile acids in mice is well established. More recently, the LXRalpha promoter has been shown to be under tight regulation by peroxisome proliferator-activated receptors (PPARs), implying a role for LXRalpha in mediating the interplay between cholesterol and fatty acid metabolism. We have studied the role of LXR in fat cells and demonstrate that LXR is regulated during adipogenesis and augments fat accumulation in mature adipocytes. LXRalpha expression in murine 3T3-L1 adipocytes as well as in human adipocytes was up-regulated in response to PPARgamma agonists. Administration of a PPARgamma agonist to obese Zucker rats also led to increased LXRalpha mRNA expression in adipose tissue in vivo. LXR agonist treatment of differentiating adipocytes led to increased lipid accumulation. An increase of the expression of the LXR target genes, sterol regulatory binding protein-1 and fatty acid synthase, was observed both in vivo and in vitro after treatment with LXR agonists for 24 h. Finally, we demonstrate that fat depots in LXRalpha/beta-deficient mice are smaller than in age-matched wild-type littermates. These findings imply a role for LXR in controlling lipid storage capacity in mature adipocytes and point to an intriguing physiological interplay between LXR and PPARgamma in controlling pathways in lipid handling.

In a systematic search for peroxisome proliferatoractivated receptor-␥ (PPAR-␥) target genes, we identified S3-12 and perilipin as novel direct PPAR-␥ target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet-associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-␥ in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-␥ therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-␥ activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain. Diabetes 53:1243-1252, 2004 T oday's western lifestyle, which involves a highcalorie diet and a lack of exercise, has led to an epidemic of obesity, which often is associated with type 2 diabetes, hypertension, hyperlipidemia, and cardiovascular disease. Increased energy intake results in an imbalance between fat synthesis and degradation, leading to an increase in circulating fatty acids (FAs) and accumulation of lipids in white adipose tissue (WAT). Whereas most tissues store triacylglycerol (TAG), cholesterol esters (CEs), or lipids in relatively small (Ͻ1 m diameter) droplets that can be used as an energy source or for membrane biogenesis, WAT stores most of the body's TAG reservoir in droplets that can exceed 50 m in diameter (1). Although the interior of those lipid droplets consists largely of neutral lipids, a number of proteins associate with the droplet surface. These include P 200 , caveolins, vimentin (1,2), mouse adipose differentiation-related protein (ADRP)/human adipophilin (hereafter referred to as adipophilin) (3), perilipin (4,5), S3-12 (6), and tail-interacting protein of 47 kDa (TIP-47) (7).Perilipin, adipophilin, and TIP-47 exhibit high sequence identity within an NH 2 -terminal motif termed PAT-1 (after perilipin, adipophilin, and TIP-47) and a more distally located PAT-2 domain (8,9). A fourth protein, S3-12, has been described along with these PAT family members. S3-12 contains a repeated 33-amino acid motif also found in adipophilin (10), and it shares protein sequence identity to both adipophilin and TIP-47 in the COOH terminus, but not to perilipin (8).At present, the lipid droplet-associating properties have been thoroughly studied only for adipophilin and perilipin (11,12). Adipophilin associates with smaller neutral lipid storage droplets located within most...

The nuclear receptor liver X receptor (LXR) ␣, an important regulator of cholesterol and bile acid metabolism, was analyzed after insulin stimulation in liver in vitro and in vivo. A time-and dose-dependent increase in LXR␣ steady-state mRNA level was seen after insulin stimulation of primary rat hepatocytes in culture. A maximal induction of 10-fold was obtained when hepatocytes were exposed to 400 nM insulin for 24 h. Cycloheximide, a potent inhibitor of protein synthesis, prevented induction of LXR␣ mRNA expression by insulin, indicating that the induction is dependent on de novo synthesis of proteins. Stabilization studies using actinomycin D indicated that insulin stimulation increased the half-life of LXR␣ transcripts in cultured primary hepatocytes. Complementary studies where rats and mice were injected with insulin induced LXR␣ mRNA levels and confirmed our in vitro studies. Furthermore, deletion of both the LXR␣ and LXR␤ genes (double knockout) in mice markedly suppressed insulin-mediated induction of an entire class of enzymes involved in both fatty acid and cholesterol metabolism. The discovery of insulin regulation of LXR in hepatic tissue as well as gene targeting studies in mice provide strong evidence that LXRs plays a central role not only in cholesterol homeostasis, but also in fatty acid metabolism. Furthermore, LXRs appear to be important insulin-mediating factors in regulation of lipogenesis.Insulin plays a major role in the regulation of carbohydrate and lipid metabolism in the liver, adipose tissue, and muscle. Hepatic fatty acid oxidation, lipogenesis, and glycerolipid synthesis are subject to regulation by insulin (for review, see Ref.