Modulation of lipid droplet size and lipid droplet proteins by trans-10,cis-12 conjugated linoleic acid parallels improvements in hepatic steatosis in obese, insulin-resistant rats.

The isomer-specific effects of conjugated linoleic acid (CLA) on hepatic steatosis were assessed in fa/fa Zucker rats, a model for insulin resistance and the metabolic syndrome. Eight weeks of feeding trans-10,cis-12 CLA significantly improved glucose tolerance without changing body weight or visceral adipose mass. The trans-10,cis-12 isomer was also associated with reduced liver lipid content, improved liver function and reduced inflammation; these effects were not observed in rats fed the cis-9,trans-11 CLA isomer. Reduced liver lipid content did not correlate with activation of AMP-activated protein kinase or suppressed activation of sterol-regulatory element binding protein-1, two key regulators of hepatic lipid metabolism. Interestingly, rats fed cis-9,trans-11 CLA had fewer cytoplasmic lipid droplets in hepatocytes compared to rats fed control diet, but these droplets were larger in size. Conversely, fa/fa rats fed the trans-10,cis-12 CLA isomer had greater numbers of hepatic lipid droplets that were smaller in size, resulting in overall lower total lipid within these droplets. Changes in lipid droplets were associated with lower hepatic levels of PERILIPIN-2 (formerly known as adipophilin) in rats fed trans-10,cis-12 CLA, whereas amounts of other members of the PERILIPIN family of lipid droplet proteins were unaffected by dietary CLA. However, CLA isomers differentially affected the subcellular localization of these proteins. Treatment of H4IIE rat hepatoma cells with CLA isomers neither prevented nor reversed, but rather induced cytoplasmic lipid droplet formation, suggesting that the anti-steatotic effects of trans-10,cis-12 CLA are likely indirect and potentially mediated via increased lipid utilization by peripheral tissues.

Altered plasma adipokines and markers of oxidative stress suggest increased risk of cardiovascular disease in First Nation youth with obesity or type 2 diabetes mellitus.

OBJECTIVE: To evaluate cardiovascular disease risk in First Nation youth with and without type 2 diabetes mellitus (T2DM) or obesity by comparing pro- and anti-inflammatory adipokines, markers of oxidative stress and the plasma phospholipid fatty acid profile. METHOD: Self-declared First Nation youth (12-15 yr) with T2DM (n = 24) as well as age-, gender-, and body mass index-matched controls (obese group; n = 19) and unmatched controls (control group; n = 34) were recruited from a pediatric diabetes clinic. RESULTS: Plasma tumor necrosis factor-alpha, ultrasensitive C-reactive protein, resistin, and total antioxidant status were not different among the three groups. Plasma total leptin, soluble leptin receptor, and free leptin were significantly higher in the T2DM group than the control group (p < 0.001, p = 0.019, p < 0.001, respectively) but did not differ from the obese group. Similarly, oxidized low-density lipoprotein was higher in the T2DM group compared with controls (p = 0.002) but not in the obese group. However, interleukin-6 was significantly higher (p < 0.001) in the T2DM group compared with both the control and the obese groups, suggesting that T2DM, but not an increase in adiposity, was responsible for this elevation. Adiponectin was significantly lower in the T2DM group compared with the control group only (p = 0.035). CONCLUSIONS: Changes in plasma adipokines and oxidative stress can already be detected in youth with T2DM; however, many of the changes are mirrored in obese youth, suggesting that both these populations are at an increased risk for future cardiovascular complications.

Dietary conjugated linoleic acid does not adversely affect bone mass in obese fa/fa or lean Zucker rats.

Conjugated linoleic acid (CLA) elevates body ash in healthy animals. The objective of the present study was to determine if single or mixed CLA isomers improve bone mass in an obese and hyperinsulinemic state. Male (n = 120) lean and obese fa/fa Zucker rats (age, 6 weeks) were randomized to 8 weeks on a control diet or to 0.4% (w/w) cis-9, trans-11 CLA (Group 1); 0.4% (w/w) trans-10, cis-12 CLA (Group 2); 0.4% (w/w) cis-9, trans-11 CLA and 0.4% (w/w) trans-10, cis-12 CLA (Group 3); 0.4% (w/w) cis-9, trans-11 CLA, 0.4% (w/w) trans-10, cis-12 CLA, and traces of other CLA isomers (Group 4); and 0.4% (w/w) cis-9, trans-11 CLA, 0.4% (w/w) trans-10, cis-12 CLA, and 0.3% (w/w) other CLA isomers (Group 5). Bone area (BA), bone mineral content (BMC), and bone mineral density (BMD) of the whole body, spine, and femur were measured at baseline (6 weeks) and at 14 weeks of age. Effects of genotype, diet, and genotype x diet interactions were assessed using factorial analysis of variance. At 6 and 14 weeks, whole-body BA and BMC were lower in lean rats compared with fa/fa rats. Similarly, at 14 weeks, fa/fa rats had a higher spine and femur BMD despite a lower femur weight. The fa/fa rats in Groups 4 and 5 had higher adjusted whole-body BMC compared with Group 3, but not with Group 1, Group 2, or the control. In lean rats, Group 3 had a greater adjusted whole-body BMC than Groups 1 and 2, but not Group 4, Group 5, or the control. Thus, commercially available CLA mixtures and single CLA isomers do not affect bone mass in a hyperinsulinemic, obese state.

Maternal supplementation with dietary arachidonic and docosahexaenoic acids during lactation elevates bone mass in weanling rat and guinea pig offspring even if born small sized.

Whether post-natal long chain polyunsaturated fatty acids (LCPUFA) elevates bone mineral content (BMC) of small and normal neonates was studied using pregnant rats and guinea pigs fed a control (C) diet or low protein (LP) diet to induce small neonates followed by C or LCPUFA diets during lactation. Measurements (days 3 and 21 post-partum) included BMC and density (BMD) plus bone metabolism. In rats LP reduced birth weight but at day 21 elevated weight and whole body BMC; LCPUFA enhanced spine BMC, tibia BMC and BMD and whole body BMD. In guinea pig pups, at days 3 and 21, LP reduced weight, whole body and regional BMC and BMD whereas LCPUFA reduced day 3 osteocalcin and elevated day 21 spine BMD. LCPUFA minimized loss of whole body BMC in dams and elevated osteocalcin in sows. LCPUFA during lactation enhances bone in normal and small neonates without compromising maternal bone.