The ability of obese people to reduce weight in the same treatment varied. Genetic make up as well as the behavioral changes are important for the successfulness of the program. One of the most proposed genetic variations that have been reported in many intervention studies was genes that control lipolysis process. This review summarizes studies that were done showing the influence of genetic polymorphisms in lipolysis pathway and weight loss in a weight loss treatment program. Some studies had shown that certain enzymes involved in this process were related to successfulness of weight loss program. Single Nucleotide Polymorphism (SNP) in PLIN (11482G>A) and ADRB3 (Trp64Arg) are the most studied polymorphisms that have effect on weight loss intervention. However, those studies were not conclusive because of limited number of subjects used and controversies in the results. Thus, replication and confirmation on the role of those genes in weight loss are important due to their potential to be used as predictors of the results of the program.
A human neuroblastoma cell line, NB-1, was treated with 24 h of microgravity simulation by clinostat, or irradiated with extremely small X-ray doses of 0.1 or 1.0 mGy using single and 10 times fractionation regimes with 1 and 2 h time-intervals. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) examination was performed for apoptosis related factors (BAX, CYTC, APAF1, VDAC1–3, CASP3, CASP8, CASP9 P53, AIF, ANT1 and 2, BCL2, MnSOD, autophagy related BECN and necrosis related CYP-40. The qRT-PCR results revealed that microgravity did not result in significant changes except for a upregulation of proapoptotic VDAC2, and downregulations of proapoptotic CASP9 and antiapoptotic MnSOD. After 0.1 mGy fractionation irradiation, there was increased expression of proapoptotic APAF1 and downregulation of proapoptotic CYTC, VDAC2, VDAC3, CASP8, AIF, ANT1, and ANT2, as well as an increase in expression of antiapoptotic BCL2. There was also a decrease in MnSOD expression with 0.1 mGy fractionation irradiation. These results suggest that microgravity and low-dose radiation may decrease apoptosis but may potentially increase oxidative stress.
Bronchial asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils at the site of inflammation. Eotaxins are potent chemoattractants for eosinophils and play important roles in pathogenesis of asthma. In the course of screening for eotaxin-3 inhibitors, we found that wogonin showed potent inhibitory activity of interleukin-4 (IL-4)-induced eotaxin-3 expression in BEAS-2B cells. In this study, we examined the effects of wogonin on IL-4/STAT6 signaling pathway and biological implication in a mouse model of asthma. Wogonin inhibited IL-4-induced activation and nuclear translocation of STAT6 which plays a key role in either the transcription of STAT6-response genes or Th2 cytokine-mediated inflammation. Oral administration of wogonin significantly reduced activation of STAT6 in the lung and the expression of eotaxin and RANTES in bronchoalveolar lavage fluids. Histological examination of lung tissue demonstrated that wogonin significantly inhibited allergen-induced eosinophilic inflammation. Administration of wogonin reduced the total IgE and ovalbumin-specific IgE levels compared with the ovalbumin-challenged group. All of these data demonstrated that wogonin could alleviate airway inflammation through inhibition of STAT6 activation induced by Th2 cytokines. Our finding implicates a potential therapeutic value of wogonin in the treatment of asthma through regulation of IL-4/STAT6 signaling pathway.
Helicobacter pylori (H. pylori) infection causes chronic gastric inflammation, peptic ulceration, and gastric carcinogenesis, in which H. pylori cytotoxin-associated gene A (CagA) plays major pathogenic action. Since transforming growth factor-β (TGF-β) and its signaling also are principally implicated in either modulating gastric mucosal inflammatory responses or causing carcinogenesis and are attenuated after H. pylori infection, we hypothesized that dysregulated Smad signaling and repressed TGF-β might be core pathogenic mechanism for H. pylori-associated gastritis or carcinogenesis. Until now, no precise underlying mechanism how deranged TGF-β signaling developed after H. pylori infection relevant to various clinical manifestations remains unclear. In this study, we examined the molecular mechanism about the inhibition of TGF-β signaling by H. pylori CagA protein. H. pylori CagA significantly suppressed TGF-β/Smad transcriptional responses through critical inhibition of Smad3, though CagA interacted constitutively with Smad2, Smad3, and Smad4. CagA inhibited TGF-β-induced suppression of proinflammatory chemokines, such as IL-8, CXCL1 and CXCL3, as well as TGF-β-induced transcription of target genes. In conclusion, repressed TGF-β signaling associated with CagA-positive H. pylori infection could be an important determinant for the outcome of H. pylori infection. Therefore, TGF-β signaling is one of the important determinants to avoid from H. pylori CagA pathogenicity.
Obesity is associated with health consequences, and thyroid dysfunction may be an adaption to the increased energy expenditure in obesity. With the rising prevalence of obesity in childhood, the prevalence of metabolic syndrome may also increase. In the current study, we have shown gender differences in the association of thyroid hormones with obesity, and attempted to elucidate the relationship between thyroid hormones and anthropometric parameters and biochemical data in obese Japanese children. We analyzed anthropometric measurements, blood pressure, body composition, thyroid hormones, and lipid profiles in 283 obese children. The association between thyroid hormones and several parameters differed by gender. The free T3 to free T4 ratio (fT3/fT4) in boys was negatively associated with the quantitative insulin sensitivity check index, whereas in girls, thyroid-stimulating hormone levels were positively correlated with levels of glucose, diastolic blood pressure, and non-high density lipoprotein-cholesterol, and fT3/fT4 was positively correlated with uric acid levels. FT3/fT4 in boys with metabolic syndrome was relatively higher than in those without metabolic syndrome. The cause of gender differences is unknown. Therefore, further studies with larger sample sizes and a long-term follow-up period are needed to address the influence of thyroid hormones on various parameters.
We assessed the effect of multi-species probiotic mixture on the changes in fecal microbiota and irritable bowel syndrome (IBS) symptoms. Eighty-one IBS patients were randomly assigned to receive either probiotic mixture (n = 39; containing Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium breve, B. actis, B. longum, and Streptococcus thermophilus) or placebo (n = 42) for 4 weeks. A questionnaire regarding general symptom relief was administered. The change in total symptom scores (sum of 10 IBS symptoms) and subtotal scores in 4 domains (pain, constipation, diarrhea, and bloating/gas) were evaluated. The change in fecal flora was determined by quantitative real-time PCR. The concentration of probiotic strains significantly increased after ingestion in probiotics group (B. bifidum, p = 0.043; B. lactis, p<0.001; L. acidophilus, p = 0.016; L. rhamnosus, p<0.001). The proportion of patients with adequate symptom relief was higher in probiotics group than in placebo group (74.4% vs 61.9%, p = 0.230). The decrease in total symptom score over time was not significantly different between the groups (p = 0.703). Among subtotal scores of 4 IBS symptom domains, the time effect was significantly different for diarrhea-symptom score between the groups (p = 0.017). A 4-week administration of multi-species probiotic mixture significantly increased the fecal concentration of most probiotic strains and improved diarrhea-symptom scores in IBS patients.
Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.
The isomaltulose based liquid formula (MHN-01), suppresses postprandial plasma glucose and insulin levels in healthy persons and patients with impaired glucose tolerance (IGT) or type 2 diabetes. MHN-01 intake as a part of breakfast also suppresses glucose and insulin levels after lunch, suggesting second meal effect. The objective of this study was to investigate the effects of nutritional counseling and long-term (24 weeks) MHN-01 ingestion on biomarkers of metabolic syndrome. Forty-one subjects with criteria of metabolic syndrome participated in this study composed with the control period (0–12 week) followed by nutritional counseling and the experimental period (12–36 week) followed by 200 kcal (837 kJ) of MHN-01 or dextrin-based standard balanced liquid formula (SBF) loading as a part of breakfast. In 16 of 41 subjects became to out of criteria for liquid formula loading study during control period (unqualified group). In the unqualified group, several biomarkers were improved. In experimental period, serum HbA1c levels significantly increased in SBF group (n = 12) but did not change in MHN-01 group (n = 10). Thus, intake of 837 kJ MHN-01 as a part of breakfast may be effective for suppression of deteriorating glucose metabolism in metabolic syndrome.
The effects of 5-aminolevulinic acid (5-ALA) on obesity were investigated using a murine model (diet-induced obese mice). Diet-induced obese mice were divided into 4 groups: a control group (C group), which was fed a high-fat diet; a low-5-ALA dose (10 mg/kg/day) group (10A group); a moderate-5-ALA dose (30 mg/kg/day) group (30A group); and a high-5-ALA dose (100 mg/kg/day) group (100A group). 5-ALA was administered by mixing the high fat diet for 8 weeks. Body weight increases in the 30A and 100A groups were significantly smaller compared with those of the C group. Body fat measurements by X-ray computed tomography indicated that the 100A group showed a tendency toward low visceral fat quantities during the final week of the study. Visceral fat weights in the 30A and 100A groups were slightly low. The levels of serum alanine aminotransferase (ALT) and total cholesterol (TC) in the 10A group was slightly low, whereas the 30A and 100A groups showed significantly lower ALT and TC values. Liver lipid concentration showed a dose-dependent decrease with ALA. Thus, in this diet-induced obese murine model, administration of 5-ALA had a significantly beneficial impact on the visceral fat, serum ALT and TC, and liver lipid concentration.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is implicated in vascular endothelial function. Vascular endothelial function is a potent regulator of arterial stiffness, an independent risk factor for cardiovascular disease. However, it is unknown whether LOX-1 is associated with arterial stiffness. Plasma concentrations of soluble LOX-1 (sLOX-1) and brachial-ankle pulse wave velocity (baPWV, an index of arterial stiffness) were measured in 143 individuals between 51 and 83 years of age. Plasma sLOX-1 concentration was correlated with baPWV (r = 0.288, p = 0.0005). In stepwise regression analysis, plasma sLOX-1 concentration was associated with baPWV, after adjusting for age; body mass index; blood pressure; heart rate; blood levels of cholesterol, triglycerides, glucose, hemoglobin A1c, and insulin; sex; and use of antihypertensives, lipid-lowering agents, and other medications (R2 = 0.575, p<0.0001). Multiple logistic regression demonstrated that plasma sLOX-1 concentration was independently associated with elevated baPWV (≥14.0 m/s; odds ratio, 1.01; 95% confidence interval, 1.00–1.03; p = 0.03). These results suggest that LOX-1 is associated with arterial stiffness.
Skin hydration is one of the primary aims of beauty and anti-aging treatments. Barley (Hordeum vulgare) and soybean (Glycine max) are major food crops, but can also be used as ingredients for the maintenance of skin health. We developed a natural product-based skin treatment using a barley and soybean formula (BS) incorporating yeast fermentation, and evaluated its skin hydration effects as a dietary supplement in a clinical study. Participants ingested a placebo- (n = 33) or BS- (3 g/day) containing drink (n = 32) for 8 weeks. A significant increase in hydration in the BS group as compared to the placebo group was observed on the faces of subjects after 4 and 8 weeks, and on the forearm after 4 weeks. Decreases in stratum corneum (SC) thickness were also observed on the face and forearm. BS enhanced hyaluronan (HA) and skin barrier function in vitro and reduced Hyal2 expression in human dermal fibroblasts (HDF). BS also recovered ultraviolet (UV) B-induced downregulation of HA in HaCaT cells. These results suggest that BS has promising potential for development as a health functional food to enhance skin health.
The anorexigenic gut hormones, cholecystokinin (CCK), glucagon-like peptide (GLP)-1 and peptide tyrosine-tyrosine (PYY), are released in response to food intake from the intestines. Dietary nutrients have been shown to stimulate these hormones. Some non-nutrients such as polyphenols show anorexigenic effects on humans. In the present study, we examined whether dietary polyphenols can stimulate secretion of these gut hormones. Caco-2 cells expressed mRNA of the gut hormones, CCK, PC1 (prohormone convertase 1), GCG (glucagon) and PYY. CCK, GLP-1 and PYY were secreted from Caco-2 cells after adding sugars, amino acids or fatty acids. Using Caco-2 cells, epigallocatechin-3-gallate (EGCG), chlorogenic acid and ferulic acid induced secretion of anorexigenic gut hormones. Particularly, EGCG induced secretion of all three hormones. In an ex vivo assay using murine intestines, EGCG also released CCK from the duodenum, and GLP-1 from the ileum. These results suggest that EGCG may affect appetite via gut hormones.