Antiobesity Effect of N-Acetylneuraminic Acid by Enhancing Antioxidative Capacity in Mice Fed a High-Fat Diet.

The sialic acid N-acetylneuraminic acid (NANA), an essential factor in bioregulation, is a functional food component that is known to have beneficial health effects, but its antiobesity effect has not been clearly understood. Adipocyte dysfunction in obesity involves a decrease in the level of NANA sialylation. In this study, we investigated the antiobesity effect of NANA in mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes. Male C57BL/6J mice were randomly divided into three groups and administered the following diets: a normal diet, an HFD, and an HFD with 1% NANA supplementation for 12 weeks. NANA supplementation significantly reduced body weight gain; epididymal adipose tissue hypertrophy; and serum lipid, fasting glucose, and aspartate transaminase levels compared with those in HFD mice. The percentage of lipid droplets in hepatic tissue was also decreased by NANA supplementation in HFD mice. The downregulation of Adipoq expression and upregulation of Fabp4 expression induced by HFD in epididymal adipocytes were improved by NANA supplementation. The downregulation of Sod1 expression and increase in malondialdehyde level were induced by HFD, and they were significantly improved in the liver by NANA supplementation, but not in epididymal adipocytes. However, NANA supplementation had no effect on sialylation and antioxidant enzyme levels in mouse epididymal adipocytes and 3T3-L1 adipocytes. Overall, NANA exerts antiobesity and antihypolipidemic effects and may be beneficial in suppressing obesity-related diseases.

Low-carbohydrate diets adversely impact the skin of a mouse model of photoaging exposed to ultraviolet B radiation.

The study results regarding the effects of low-carbohydrate (LC) diets remain controversial; hence further research is required to assess their safety. Here, we examined whether LC diets cause skin damage in C57BL/6J mice. Six-week-old female mice (n = 20) were fed an LC (protein/fat/carbohydrate energy ratio = 35:45:20) or control diet ad libitum for eight weeks, after which their backs were shaved, and a subset of the mice were exposed to ultraviolet B radiation thrice per week. Ultraviolet B irradiation induced wrinkle formation on the skin surface, and thickening of the epidermis, which was also noticeable in the LC diet-fed mice in the absence of ultraviolet B radiation. Meanwhile, the number of epidermal melanocytes and degree of horny layer keratosis increased in the LC diet-fed mice following ultraviolet B irradia-tion. mRNA expression analysis of the liver and skin showed decreased levels of the antioxidant enzyme superoxide dismutase 1 following ultraviolet B irradiation only in the LC diet-fed mice. Alternatively, the expression of pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-1ß, increased in response to ultraviolet B radiation and LC diet intake. Hence, LC diets may adversely affect skin morphology and exacerbate the effects of ultraviolet B irradiation, which may be associated with anti-oxidant dysfunction.

Low-Carbohydrate Diet Inhibits Different Advanced Glycation End Products in Kidney Depending on Lipid Composition but Causes Adverse Morphological Changes in a Non-Obese Model Mice.

Low carbohydrate diets (LC diets) have been noted for adverse health effects. In addition, the effect of lipid composition on an LC diet is unclear. In this study, we used an LC diet containing two different lipids, lard (LC group) and medium-chain triglyceride oil (MCT-LC group), to examine the effect of an LC diet in non-obese mice. Male C57BL/6J mice were fed the control diet or one of the experimental diets ad libitum for 13 weeks. Increased renal weight and glomerular hypertrophy, as well as enlargement of intraglomerular small vessels with wall thickening, were seen in the LC and MCT-LC groups. Renal AMP-activated protein kinase activity was significantly decreased only in the LC diet group. On the other hand, epididymal adipose tissue weight and adipocyte area were markedly decreased only in the MCT-LC group. A positive effect was also observed in the kidney, where different advanced glycation end products, Nε-(carboxyethyl)-lysine and Nε-(carboxymethyl)-lysine, were inhibited depending on the lipid composition of the LC diet. Our findings suggest that, in non-obese conditions, low dietary intake of carbohydrates had both positive and negative impacts. The safety of diets low in carbohydrates, including the effects of fatty acid composition, requires further investigation.

The Inhibitory Role of α2,6-Sialylation in Adipogenesis.

Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases. Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear. In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice. We found that a gene encoding ß-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice. We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells. Using proteomic analysis, integrin-ß1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding. St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase. Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding. The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing. Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-ß1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.

The effects of moderate exercise on secretory IgA production in mice depends on dietary carbohydrate intake.

Secretory immunoglobulin A (sIgA) is produced from intestinal mucosa and is essential in preventing infection. We analyzed the influence of moderate exercise on intestinal sIgA production and antioxidative function under different carbohydrate nutritional conditions. Thirty-six mice were fed an experimental diet for 10 weeks-a high-carbohydrate (HC) diet, a low-carbohydrate (LC) diet, or a control (C) diet. After 1 week on the experimental diets, mice were divided into sedentary and exercise groups (n = 6/group), where the exercise consisted of treadmill running for 30 min/day at 11 m/min for 6 days/week in 9 consecutive weeks. Intestinal sIgA levels in the exercise groups fed C or LC diets were significantly lower compared with the parallel sedentary groups, or exercise-group mice fed HC diet. Expression of the polymeric immunoglobulin receptor (pIgR) in the small intestine was significantly higher in the exercise group fed a HC diet. Superoxide dismutase activity in the small intestine was higher in the exercise group than in the sedentary group, with no effects resulting from intake carbohydrate levels. Our results indicated that moderate exercise reduced the levels of intestinal sIgA depending on decreasing of carbohydrate intake, which is connected with the expression of pIgR.

Nutritional status in relation to adipokines and oxidative stress is associated with disease activity in patients with rheumatoid arthritis.

OBJECTIVE: We assessed whether disease activity was associated with dietary habits, nutritional status, adipokines, and oxidative stress in patients with rheumatoid arthritis. METHODS: The subjects were 37 patients with RA. The assessment of the nutritional status included anthropometric and biochemical parameters. A food-frequency questionnaire and a 3-d diet record to assess dietary intake were used. The serum levels of adipokines and oxidative stress markers in sera and saliva were measured. The disease activity was determined using the 28 Disease Activity Score (DAS28). We divided the subjects into high (DAS28 ≥3.2) and low (DAS28 <3.2) disease activity groups. RESULTS: The serum leptin and albumin levels were significantly lower, whereas the inflammatory markers were increased, in the high disease activity group. The dietary intake assessment showed a lower intake of fish oil and a lower ratio of monounsaturated fatty acid intake in the high disease activity group. There was a negative correlation between the DAS28 and the dietary intake of the ratio of monounsaturated fatty acid to total fatty acid intake. The serum oxidative stress marker (reactive oxygen metabolites) showed a positive correlation to the DAS28. The salivary reactive oxygen metabolites also correlated with C-reactive protein and serum reactive oxygen metabolites. CONCLUSION: Altered serum adipokine levels with decreased albumin may reflect the deterioration that is associated with rheumatoid arthritis. An increased oxidative stress was observed in sera and saliva. Intakes of ω-3 polyunsaturated fatty acids, fish oil, and monounsaturated fatty acid seem to affect disease activity and may have beneficial effects by decreasing inflammation.

Nutritional status is strongly correlated with grip strength and depression in community-living elderly Japanese.

OBJECTIVES: To evaluate the utility of the Mini-Nutritional Assessment (MNA) in assessing nutritional, physical and psychosocial functions in community-living elderly individuals. DESIGN: A cross-sectional study of elderly individuals investigated in August 2007 and August-September 2008. Nutritional status was assessed using serum biomarkers, anthropometric measurements and the MNA. Physical function was assessed by measuring grip strength and both usual and maximum walking speeds. The Geriatric Depression Scale (GDS) was used to measure the individual's depressive state. SETTING: Elder-care facilities in Tokyo, Japan. SUBJECTS: Community-living elderly individuals aged ≥65 years (n 130). RESULTS: The MNA evaluation classified twenty-seven (20·8 %) individuals as being at risk for malnutrition (MNA score ≤23·5); these at-risk individuals included a high proportion of the elderly aged ≥75 years. MNA scores correlated with nutritional biomarkers (total protein, albumin, cholinesterase, Hb) and anthropometric measurements (triceps skinfold, subscapular skinfold, mid-arm muscle area) and exhibited a strong correlation with grip strength and GDS score. Multivariate analysis revealed that grip strength, GDS score, marital status and maximum walking speed are strong predictors of MNA score. CONCLUSIONS: The MNA is considerably useful in providing a comprehensive assessment of nutritional status in elderly, community-living Japanese. However, larger-scale epidemiological studies are needed to determine the utility and the appropriate cut-off point of the MNA as a screen for risk of malnutrition.

The influence of a high-fat dietary environment in the fetal period on postnatal metabolic and immune function.

Few reports show whether a high-fat (HF) dietary environment in the fetal period affects immune function or the development of lifestyle-related disease at maturity. We examined the influence of an HF dietary environment in the fetal period on postnatal metabolic and immune function. A total of 16 pregnant mice were given control (CON) diet and 16 were given HF diet in the gestational period, from mating to delivery. After delivery lactating mice were given either CON or HF diet, resulting in four groups. After weaning, the offspring mice were given the same diet that their mothers received during lactation. HF dietary intake in the postnatal period increased fat pad weights, serum glucose, and leptin levels. An HF diet in the fetal period resulted in fewer splenic lymphocytes, a thinner thymic cortex, and impaired antigen-specific immune reactions. Furthermore, tumor necrosis factor (TNF)-alpha production and serum triglyceride levels were elevated in the fetal HF group. In addition, the HF-HF group showed a consistent decrease in ovalbumin (OVA)-specific IgG and elevation of IgE, associated with advanced fatty changes in the liver. Results from this study suggest that HF environment during the fetal period induces epigenetic propensity toward obesity and immunological burden in part due to increased adipose tissue mass, significant reduction in the number of immune cells and decreased activities of immune cells.

Improvement of nutritional status and incidence of infection in hospitalised, enterally fed elderly by feeding of fermented milk containing probiotic Lactobacillus johnsonii La1 (NCC533).

Probiotics have potential to improve host immunity; however, there is less evidence showing their efficacy against infections and nutritional status in the elderly. We conducted a double-blinded feeding trial in the elderly to elucidate the effect of fermented milk containing Lactobacillus johnsonii La1 (LC1) on infections and nutritional status. Twenty-four completely enterally fed elderly in-patients aged over 70 years were randomly assigned into two groups. All subjects were administered 3768 kJ (900 kcal)/d of total enteral nutrition (EN) through tube feeding for 12 weeks. Subjects in the LC1 group were administered 373 kJ (89 kcal)/d of LC1 fermented milk after feeding of 3395 kJ (811 kcal)/d of EN for 12 weeks. In the control group, 373 kJ/d of the same EN was replaced from the fermented milk. In the LC1 group, the percentage of days with infections during the run-in observation period was 15.4 (SD 17.3) %, which significantly decreased to 5.7 (SD 8.1) % during the intervention period (P = 0.018), and the reduction was larger than that of the control group (P = 0.047). Blood Hb increased (P < 0.05), and there was a tendency towards an increase in serum albumin and a decrease in TNF-alpha (a pro-inflammatory cytokine) in the LC1 group. There was a trend towards an increase in blood phagocytic activity (a natural immunity marker) in the subjects whose initial level was low in the LC1 group. There were no changes in those parameters in the control group. Administration of fermented milk containing the probiotic L. johnsonii La1 may contribute to suppressing infections by improving nutritional and immunological status in the elderly.

Effect of Lactobacillus johnsonii La1 on immune function and serum albumin in aged and malnourished aged mice.

OBJECTIVE: Protein-energy malnutrition (PEM) is a serious nutritional problem that causes immune dysfunction in elderly people. Probiotic lactic acid bacteria may potentially modify immunity; however, there is little evidence to elucidate the influence of these bacteria on PEM in the elderly. METHODS: The immune modulation effects of lactic acid bacterium Lactobacillus johnsonii La1 (La1) were examined in aged mice and aged mice with PEM. Twenty-month-old male 57BL6/n mice (n = 28) were divided into four groups and received the following diet for 14 d: a complete diet (20% protein) without Lal (control) or with Lal or a low-protein diet (5% protein) to induce PEM, with or without La1. All mice were immunized with diphtheria toxin (DT) with alfacalciferol at 7 d and sacrificed 14 d after starting the experimental diets. RESULTS: Serum albumin concentrations and body weight, both of which were reduced by the low-protein diet, were ameliorated by La1 intake and were the same as in mice receiving the control diet. Anti-DT immunoglobulin (Ig) A in fecal extract was increased by La1 intake in mice receiving the complete and low-protein diets. Serum anti-DT IgA, IgG, splenocyte proliferation, and CD8(+) T cells were reduced by the low-protein diet and restored by La1 intake. CONCLUSION: La1 enhances intestinal IgA production and helps recover nutritional status and systemic immune responses in aged mice with PEM. It is possible that La1 may contribute to immune system recovery in immunocompromised hosts such as elderly humans with PEM.

Oral-tolerance induction in diet-induced obese mice.

OBJECTIVE: It is known that immune functions are altered in various ways by obesity. However, changes in the intestinal immune system resulting from obesity remain poorly understood. Oral tolerance is a system that suppresses antigen specific immune responses to orally administrated antigens. The intestinal immune system is intimately associated with the oral tolerance system, that acts to prevent allergic and inflammatory diseases. In this study we investigated the effect of obesity on induction of oral tolerance to ovalbumin (OVA) in an animal model of obesity. RESEARCH METHODS AND PROCEDURES: Obese mice induced by a high fat diet and control mice were allowed free access for 3 days to a 1%-ovalbumin (OVA) solution in drinking water. After continuous feeding of the antigen, all the mice were immunized by two intraperitoneal injections of OVA administered 7 days apart. RESULTS: In the control mice, induction of oral tolerance caused an increase in antigen specific IgG1 levels and a decrease in IgG2a levels. In contrast, the IgG1/IgG2a ratio was reversed in obese mice. OVA-specific IL-2 production was suppressed by antigen feeding in both the control and obese mice; however, suppression of OVA-specific IL-10 was observed only in the control mice. Although OVA-specific IgA and IgM were not affected by antigen feeding, the obese groups of mice had significantly lower titers of antibodies. DISCUSSION: These findings suggest that obesity may affect induction of oral tolerance following antigen feeding and that these changes may be related to the inflammatory reaction.