Decaffeinated green tea extract rich in epigallocatechin-3-gallate improves insulin resistance and metabolic profiles in normolipidic diet--but not high-fat diet-fed mice.

Supplementation with epigallocatechin-3-gallate (EGCG), which restores metabolic profiles, has been proposed as an option for preventing and treating obesity. We investigated whether decaffeinated green tea extract rich in EGCG, attenuates high-fat diet (HFD)-induced metabolic alterations in Swiss mice. The mice were maintained on either a control diet (CD) or HFD for 8 weeks and supplemented with either a placebo or EGCG (50mg/kg/day). Body weight, serum lipid profiles, cytokine protein expression, and content in epididymal (EPI) and retroperitoneal (RET) adipose tissues, and adipocyte area were measured. The body weights of HFD + placebo-fed mice were increased compared with those of HFD + EGCG-fed mice (28 and 21%, respectively), whereas the body weights of CD + EGCG-fed mice were decreased 16% compared with those of the CD + placebo group. Serum triglyceride levels were decreased 32% in the CD + EGCG group compared with the CD + placebo group. Compared with the CD + placebo group, increased phosphorylation of AMPK and hormone-sensitive lipase in EPI and RET, respectively, was found in the CD + EGCG group. Increased acetyl-CoA carboxylase phosphorylation was observed in both adipose tissues. In addition, TNF-α and IL-10 levels in EPI and adiponectin levels were higher in the CD + EGCG group than in the CD + placebo group. TNF-α levels were lower in the HFD + EGCG group than in the HFD + placebo group. Furthermore, the CD + EGCG group exhibited a lower adipocyte area than the CD + placebo group. These indicate that the effects of decaffeinated green tea extract on body mass may be related to the crosstalk between lipolytic and inflammatory pathways in normolipidic diet-fed mice but not in HFD-fed mice.

Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-κB pathway in 3T3-L1 adipocytes.

Adiponectin and interleukin 10 (IL-10) are adipokines that are predominantly secreted by differentiated adipocytes and are involved in energy homeostasis, insulin sensitivity, and the anti-inflammatory response. These two adipokines are reduced in obese subjects, which favors increased activation of nuclear factor kappa B (NF-κB) and leads to elevation of pro-inflammatory adipokines. However, the effects of adiponectin and IL-10 on NF-κB DNA binding activity (NF-κBp50 and NF-κBp65) and proteins involved with the toll-like receptor (TLR-2 and TLR-4) pathway, such as MYD88 and TRAF6 expression, in lipopolysaccharide-treated 3T3-L1 adipocytes are unknown. Stimulation of lipopolysaccharide-treated 3T3-L1 adipocytes for 24h elevated IL-6 levels; activated the NF-κB pathway cascade; increased protein expression of IL-6R, TLR-4, MYD88, and TRAF6; and increased the nuclear activity of NF-κB (p50 and p65) DNA binding. Adiponectin and IL-10 inhibited the elevation of IL-6 levels and activated NF-κB (p50 and p65) DNA binding. Taken together, the present results provide evidence that adiponectin and IL-10 have an important role in the anti-inflammatory response in adipocytes. In addition, inhibition of NF-κB signaling pathways may be an excellent strategy for the treatment of inflammation in obese individuals.

Supplementing alpha-tocopherol (vitamin E) and vitamin D3 in high fat diet decrease IL-6 production in murine epididymal adipose tissue and 3T3-L1 adipocytes following LPS stimulation.

BACKGROUND: It is well known that high fat diets (HFDs) induce obesity and an increase in proinflammatory adipokines. Interleukin-6 (IL-6) is considered the major inflammatory mediator in obesity. Obesity is associated with a vitamin deficiency, especially of vitamins E and D3. We examined the effects of vitamin D3 and vitamin E supplementation on levels of IL-6 and IL-10 (as a marker of anti-inflammatory cytokines since, a balance between pro- and anti-inflammatory cytokines is maintained) protein expression in adipose tissue of mice provided with an HFD. Additionally, we measured the effects of vitamin E and vitamin D3 treatment on LPS-stimulated 3T3-L1 adipocytes IL-6 and IL-10 secretion. RESULTS: IL-6 protein levels and the IL-6/IL-10 ratio were decreased in epididymal white adipose tissue in groups receiving vitamins E and D3 supplementation compared to the HFD group. A 24-hour treatment of vitamin D3 and vitamin E significantly reduced the IL-6 levels in the adipocytes culture medium without affecting IL-10 levels. CONCLUSIONS: Vitamin D3 and vitamin E supplementation in an HFD had an anti-inflammatory effect by decreasing IL-6 production in epididymal adipose tissue in mice and in 3T3-L1 adipocytes stimulated with LPS. Our results suggest that vitamin E and D3 supplementation can be used as an adjunctive therapy to reduce the proinflammatory cytokines present in obese patients.

Depot-specific modulation of adipokine levels in rat adipose tissue by diet-induced obesity: the effect of aerobic training and energy restriction.

The present study examined the effects of aerobic training and energy restriction on adipokines levels in mesenteric (MEAT) and retroperitoneal (RPAT) white adipose tissue from obese rats. Male Wistar rats were fed with standard laboratory diet (Control group) or high fat diet (HFD). After 15 weeks, HFD rats were randomly assigned to the following groups: rats submitted to HFD, which were sedentary (sedentary HFD, n=8) or trained (trained HFD, n=8); or submitted to energy-restriction (ER), which were sedentary (sedentary ER, n=8) or trained (trained ER, n=8). Trained rats ran on a treadmill at 55% VO(2max) for 60 min/day, 5 days/week, for 10 weeks. ER rats were submitted to a reduction of 20% daily caloric ingestion compared to the Control group. ER and aerobic training decreased body weight, MEAT and RPAT absolute weight, and fat mass. IL-6, IL-10 and TNF-α levels were decreased and adiponectin did not change in RPAT in response to ER protocol. On the other hand, ER and the aerobic training protocol decreased IL-6, TNF-α and adiponectin levels in MEAT. Absolute MEAT weight showed a positive correlation with IL-6 (r=0.464), TNF-α (r=0.508); and adiponectin (r=0.342). These results suggest a tissue-specific heterogeneous response in adipokines level. The combination of the protocols (aerobic training and energy restriction) did not induce an enhanced effect.