Long term effects of high fat and sucrose diets on obesity and lymphocyte proliferation in mice.

OBJECTIVE: To clarify the effect of prolonged feeding of a high-fat and sucrose, and to clarify the effect of sucrose instead of other carbohydrate on obesity and immunity in C57BL/6J mice. METHODS: We investigated the development of obesity and immune cell function in four groups of mice fed high-fat, high-fat plus high-sucrose, high-sucrose, and control diet for 7 months. RESULTS: Mice fed high-fat and high-fat plus high-sucrose groups developed severe obesity. Body weight, adipose tissue weight, serum leptin, blood glucose, and insulin were significantly higher, while the level of serum soluble leptin receptor was significantly lower in mice fed high-fat and high-fat plus high-sucrose diets than in mice fed the control or high-sucrose diets. Splenocyte proliferation stimulated by T-cell mitogen (PHA, ConA, and anti-CD 3 antibody) and B-cell mitogen (LPS) was significantly lower in both obese, high-fat and high-fat plus high-sucrose groups than in control and high-sucrose groups. However, these parameters did not differ between high-fat and high-fat plus high-sucrose groups. CONCLUSIONS: Long-term feeding of high-fat diet and high-fat plus high-sucrose diet similarly induced severe obesity in C57BL/6J mice. Not only T-cell, but also B-cell function may be impaired in mice made severely obese by the high-fat or high-fat plus high-sucrose diets.

Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester.

OBJECTIVE: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women in early pregnancy. DESIGN: A cross-sectional, observational study. SUBJECTS: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were not consuming any folate supplements or folate fortified foods. METHODS: Three-day dietary records were obtained from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers. Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate group (serum folate > or = 9 ng/ml). RESULT: Mean serum and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels were remarkably higher than the reported values from many other countries despite our subjects receiving no folic acids supplements. However, mean folate intake by our subjects from natural foods was 289 microg/day, which is thought to be low according to the Japanese dietary recommendation specified for pregnant women. The intake of spinach and fruits was significantly greater in the high folate group than in the low folate group. CONCLUSION: Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in Japanese pregnant women in the first trimester, although the intake of folate from natural food was not high enough to meet the recommended daily intake.

Analysis of the effect of leptin on immune function in vivo using diet-induced obese mice.

Leptin can regulate several immune functions. However, the role of leptin on lymphocyte function has not been recognized in vivo. Accordingly, we have investigated the effect of leptin on starvation-induced immune dysfunction using diet-induced obese mice. To induce obesity, C57BL/6J mice were fed a high-fat diet for 14 weeks and control mice were fed a standard diet for the same period. The obese and control groups of mice were then starved for 48 h, and received intraperitoneal injections of recombinant leptin or phosphate-buffered saline four times during starvation. Other control mice in both diet groups were free fed without being starved. Although starvation of the control mice dramatically reduced the weights of the immune organs, cytokine production and increased proliferation of cultured splenocytes, these levels returned to those of the free-feeding groups with exogenous leptin administration. However, these effects of leptin were not observed in obese mice. These findings provide some evidence that leptin can regulate the immune function in vivo. It is also suggested that the action of leptin might not appear in obesity.

Effect of obesity and insulin on immunity in non-insulin-dependent diabetes mellitus.

OBJECTIVE: To understand the effect of obesity and insulin on immune functions in non-insulin-dependent diabetes mellitus (NIDDM). SUBJECT: Fourteen obese NIDDM (body mass index (BMI)=30.6+/-1.1), seven non-obese NIDDM (BMI=24.2+/-0.5) and five obese non-NIDDM (BMI=28.3+/-0.67). INTERVENTIONS: We first examined the influence of insulin on the proliferation of several human cell lines. Second, we compared several immune functions between obese and non-obese NIDDM, and obese non-NIDDM patients using peripheral blood mononuclear cells. RESULT: Insulin decreased proliferation of T-cell lines but not that of other types of cell lines. Furthermore, obesity augmented the production of IL-1beta which could have cytotoxity against islet beta cells in NIDDM. CONCLUSION: Our data suggested that the pathophysiology of NIDDM could be affected by the change of immunity due to obesity, and the treatment of obesity in NIDDM may be important from an immunological aspect.

Change of cytokine balance in diet-induced obese mice.

Although decreased T-cell function has been observed in obese human subjects and genetically obese animals, the precise role of immune functions in obesity is still unclear. To investigate immune functions in obesity, we examined the proliferative responses of splenic lymphocytes and their capacity to produce cytokines in the presence or absence of leptin, the protein produced by the obese gene, in diet-induced obese and control mice. For induction of obesity, C57BL/6J mice were fed a high-fat diet for 13 weeks. In mice fed the high-fat diet, body weight, fat pad weight, and tumor necrosis factor (TNF) alpha production by adipocytes were significantly increased relative to mice fed the normal diet. Lipopolysaccharide (LPS) stimulated proliferation of cultured splenocytes from diet-induced obese mice was also increased. However, production of interleukin (IL)-2 by splenic lymphocytes from obese mice was suppressed, whereas interferon (IFN)-gamma and IL-4 production was increased. Exogenous lepitn regulated the cytokine production by cultured splenocytes from control and obese mice, respectively (upregulation of IFN-gamma and downregulation of IL-2 in control mice, and downregulation of IL-4 in obese mice). These results suggest that changes in cytokine production by splenic lymphocytes in obesity are indicative of altered immune functions that might contribute to related complications, although the effect of difference in nutrient intake (macro and micro) may also have contributed to the changes.

Sugar regulates mRNA abundance of H(+)-ATPase gene family members in tomato.

The plant plasma membrane H(+)-ATPase energizes the secondary uptake of nutrients and may facilitate cell expansion by acidifying the cell wall. In yeast, Glc stimulates the accumulation of H(+)-ATPase mRNA, and the growth rate supported by various sugars is correlated with H(+)-ATPase protein abundance. Expression of three H(+)-ATPase genes, LHA1, LHA2, and LHA4, was previously detected in tomato (Lycopersicon esculentum). We have characterized the sequence of the LHA4 gene and examined the expression of these three tomato H(+)-ATPase genes in growing tissues and in response to exogenous sugars. LHA4 is a member of the H(+)-ATPase subfamily, including the Arabidopsis thaliana genes AHA1, AHA2, and AHA3. The 5' untranslated region of the deduced LHA4 cDNA contains a short, open reading frame very similar to that in the Nicotiana plumbaginifolia gene PMA1. LHA4 transcript abundance in seedlings is correlated with cell growth, being 2.5 times greater in hypocotyls of dark- versus light-grown plants. The accumulation of both LHA4 and LHA2 mRNAs is induced by the addition of exogenous sugars and this induction appears to be dependent on sugar uptake and metabolism, because mannitol and 3-O-methylglucose do not stimulate mRNA accumulation. These results suggest that the induction of expression of H(+)-ATPase genes by metabolizable sugars may be part of a generalized cellular response to increased cell growth and metabolism promoted by the availability of an abundant carbon source.

The diageotropica mutation and synthetic auxins differentially affect the expression of auxin-regulated genes in tomato.

The effect of a tomato (Lycopersicon esculentum) mutation, diageotropica (dgt), on the accumulation of mRNA corresponding to tomato homologs of three auxin-regulated genes, LeAux, LeSAUR, and Lepar, was examined. The dgt mutation inhibited the induction of LeAux and LeSAUR mRNA accumulation by naphthalene acetic acid (NAA) but had no effect on NAA-induced Lepar mRNA accumulation. The effect of two synthetic auxins, NAA and 3,7-dichloro-8-quinoline carboxylic acid (quinclorac), on the accumulation of LeAux, LeSAUR, and Lepar mRNA was also examined. Quinclorac induced the expression of each of the auxin-regulated genes, confirming its proposed mode of herbicidal action as an auxin-type herbicide. Concentrations of quinclorac at least 100-fold higher than NAA were required to induce LeAux and LeSAUR mRNA accumulation to similar levels, whereas Lepar mRNA accumulation was induced by similar concentrations of NAA and quinclorac. Collectively, these data suggest the presence of two auxin-dependent signal transduction pathways: one that regulates LeSAUR and LeAux mRNA accumulation and is interrupted by the dgt mutation and a second that regulates Lepar mRNA accumulation and is not defective in dgt tomato hypocotyls. These two auxin-regulated signal transduction pathways can be further discriminated by the action of two synthetic auxins, NAA and quinclorac.

Assignment of most genes encoding major peroxisomal polypeptides to chromosomal band V of the asporogenic yeast Candida tropicalis.

The peroxisomes of the asporogenic yeast Candida tropicalis contain about 20 major polypeptides (PXPs). We have isolated a number of genes encoding them; 11 POX genes encoded independent PXPs and three POY genes were likely to encode three other PXPs. To locate these genes on the chromosomes, chromosomes of C. tropicalis were separated by pulsed-field gel electrophoresis. Eight chromosomal bands were observed over the range of 1.0 Mbp (band 1) to 2.8 Mbp (band VIII); the genome size was estimated to be about 20 Mbp. Southern blot analysis showed that ten genes were on band V, three genes were on band IV, and the other gene was on band VI. Three genes gave hybridization signals of nearly equal intensity on two different chromosomal bands: POX6A and POX8B, on bands V and VII; and POX8A, on bands IV and VI. Ribosomal RNA genes also hybridized to two bands, VI and VII. Most genes assigned to only one band hybridized to two restriction fragments produced by either NotI or SfiI endonuclease. The results suggested that C. tropicalis was diploid and that restriction sites were conserved little between homologues. The three POX genes that were found on two chromosomal bands hybridized to not more than two restriction fragments, implying that the allelic genes were present on different chromosomal bands.

Studies on a new herbicidal antibiotic, homoalanosine.

Homoalanosine having a herbicidal activity was isolated from the culture filtrate of a soil isolate SC-1688 which was classified as Streptomyces galilaeus. The chemical structure of homoalanosine was determined to be L-2-amino-4-nitrosohydroxyaminobutyric acid by analyses of spectral and biological data. The antibiotic has high herbicidal activity at low concentrations against especially common cocklebur and ladysthumb among the tested weeds and crops. Foliar application of this antibiotic inhibited the growth of roots and buds. This result indicated that homoalanosine had a systemic herbicidal activity.