Galectin-9 Induced by Dietary Prebiotics Regulates Immunomodulation to Reduce Atopic Dermatitis Symptoms in 1-Chloro-2,4-Dinitrobenzene (DNCB)-Treated NC/Nga Mice.

Atopic dermatitis (AD) is a skin disorder that causes chronic itch. We investigated the inhibitory effects of a mixture of prebiotic short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS), inulin, or ß-glucan on AD development in 1-chloro-2,4- dinitrobenzene (DNCB)-treated NC/Nga mice. Mice were randomly assigned to six groups: untreated mice, AD control, positive control (DNCB-treated NC/Nga mice fed a dietary supplement of Zyrtec), and DNCB-treated NC/Nga mice fed a dietary supplement of prebiotics such as scGOS/lcFOS (T1), inulin (T2), or ß-glucan (T3). The prebiotic treatment groups (T1, T2, and T3) showed suppression of AD symptoms, Th2 cell differentiation, and AD-like skin lesions induced by DNCB. In addition, prebiotic treatment also reduced the number of microorganisms such as Firmicutes, which is associated with AD symptoms, and increased the levels of Bacteroidetes and Ruminococcaceae, which are associated with alleviation of AD symptoms. Our findings demonstrate the inhibitory effects of prebiotics on AD development by improving the Th1/Th2 cytokine balance and beneficial symbiotic microorganisms in in vitro and in vivo models.

Effects of Vitamin C or E on the Pro-inflammatory Cytokines, Heat Shock Protein 70 and Antioxidant Status in Broiler Chicks under Summer Conditions.

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between 32°C to 34°C at day to 27°C to 29°C at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

Effects of cyclic heat stress or vitamin C supplementation during cyclic heat stress on HSP70, inflammatory cytokines, and the antioxidant defense system in Sprague Dawley rats.

A total of 21 male SD rats were divided into three groups to investigate the effects of consecutive cyclic heat stress or vitamin C under heat stress on heat shock protein (HSP) 70, inflammatory cytokines, and antioxidant systems. The heat stress (HS) and vitamin C supplementation during heat stress (HS+VC) groups were exposed to cyclic heat stress (23 to 38 to 23°C) for 2 h on each of seven consecutive days. The HS+VC group had free access to water containing 0.5% vitamin C throughout the experiment. Hepatic HSP70 mRNA in the HS group was significantly (P<0.05) higher than that in the control (CON) or HS+VC group. The mRNA levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in the HS group were greater (P<0.05) than those in the CON group. The HS+VC group showed significantly (P<0.05) lower mRNA levels of hepatic interleukin-6 and TNF-α than the HS group. However, thymic HSP70 and inflammatory cytokines were unaffected by treatments. In the hepatic antioxidant system, the mRNA and activity of glutathione peroxidase (GPX) were greater (P<0.05) in the HS than in the CON group, whereas the HS+VC group showed markedly (P<0.05) lower GPX mRNA and activity than the HS group. However, superoxide dismutase, glutathione S-transferase, and malondialdehyde were unaffected by treatments. In conclusion, cyclic heat stress activated hepatic HSP70, TNF-α, iNOS, and GPX genes, whereas vitamin C during heat stress ameliorated heat stress-induced cellular responses in rats.

Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1).

Preadipocyte factor-1 (Pref-1) is a transmembrane protein highly expressed in preadipocytes. Pref-1 expression is, however, completely abolished in adipocytes. The extracellular domain of Pref-1 undergoes two proteolytic cleavage events that generate 50 and 25 kDa soluble products. To understand the function of Pref-1, we generated transgenic mice that express the full ectodomain corresponding to the large cleavage product of Pref-1 fused to human immunoglobulin-gamma constant region. Mice expressing the Pref-1/hFc transgene in adipose tissue, driven by the adipocyte fatty acid-binding protein (aP2, also known as aFABP) promoter, showed a substantial decrease in total fat pad weight. Moreover, adipose tissue from transgenic mice showed reduced expression of adipocyte markers and adipocyte-secreted factors, including leptin and adiponectin, whereas the preadipocyte marker Pref-1 was increased. Pref-1 transgenic mice with a substantial, but not complete, loss of adipose tissue exhibited hypertriglyceridemia, impaired glucose tolerance, and decreased insulin sensitivity. Mice expressing the Pref-1/hFc transgene exclusively in liver under the control of the albumin promoter also showed a decrease in adipose mass and adipocyte marker expression, suggesting an endocrine mode of action of Pref-1. These findings demonstrate the inhibition of adipogenesis by Pref-1 in vivo and the resulting impairment of adipocyte function that leads to the development of metabolic abnormalities.

Suppression of fatty acid synthase promoter by polyunsaturated fatty acids.

Dietary polyunsaturated fat is known to suppress expression of fatty acid synthase (FAS), a central enzyme in de novo lipogenesis. The sterol regulatory element-binding protein (SREBP) has recently been shown to be involved in this suppression. We previously reported that the first 2.1 kb of the FAS promoter are sufficient for transcriptional induction by a high carbohydrate diet as well as suppression by polyunsaturated fat in transgenic mice. Here, we first examined the DNA sequences responsible for SREBP-mediated suppression of FAS promoter activity by polyunsaturated fatty acids (PUFA) in vivo. Feeding polyunsaturated fat prevented both the low-level activation of the -278 FAS promoter which contains the -150 sterol response element (SRE), as well as the maximal activation of the longer -444 FAS promoter. We observed that ectopic expression of the activated form of SREBP in liver prevented PUFA-mediated suppression of both the endogenous FAS and FAS promoter-reporter transgene expression. We also found that the promoter region required for PUFA suppression in vivo is located between -278 to -131, where SREBP functions. Using HepG2 cells, we further examined the specific FAS promoter elements required for PUFA suppression. We found that the -150 SRE, as well as the -65 E-Box, contribute to PUFA suppression of the FAS promoter, at least in vitro.