Dietary soy phytoestrogens and ERalpha signalling modulate interferon gamma production in response to bacterial infection.

Diets rich in soy phytoestrogens have many potential health benefits but isoflavones such as genistein may suppress cell mediated immune function. The effect of dietary phytoestrogens on the host response to infection has not been extensively examined. Mice were fed a diet containing soy phytoestrogens and infected with Mycobacterium avium to establish a chronic infection and inflammatory response. As phytoestrogens may act through classical oestrogen receptors (ER), mice deficient in ERalpha signalling and wild type mice were evaluated for a panel of Type 1-associated cytokines (IFNgamma, IL-12 and IL-18) in the spleen. IFNgamma production in the spleen was increased approximately 4-fold in ERalpha-deficient mice fed a casein-based diet over wild type mice fed a casein-based diet (P < 0.05), suggesting a role for ERalpha in suppressing IFNgamma production. IL-18 levels in spleens of wild type mice were decreased compared to ERalpha-deficient mice on a casein diet. Splenic IL-12 and IL-18 levels were not affected in wild type and ERalpha-deficient mice on the phytoestrogen containing diets, with the exception that whole soy increased IL-12 levels in the tissues of ERalpha deficient mice. We conclude that ERalpha and dietary phytoestrogens can influence production of key regulatory cytokines in response to chronic bacterial infection.

Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER alpha KO, mice.

Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ER alpha WT) and estrogen receptor-alpha knockout (ER alpha KO) mice. ER alpha WT and ER alpha KO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ER alpha WT and ER alpha KO mice fed genistein consuming less food (p < 0.0001) and subsequently weighing less than mice fed the control diet (p < 0.0001). Significant differences in food intake by genotype were also observed (p = 0.0017), with ER alpha KO mice consuming less than ER alpha WT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential adverse effect on tumor development when high levels of genistein are consumed.

Insulin-like growth factor-I and II receptor expression in rat colon mucosa are affected by dietary lipid intake.

Epidemiologic data and animal models have demonstrated a correlation between dietary fat composition and colon cancer risk. We have previously found that dietary fat alters cell proliferation in rat colon, which may influence the risk of colon cancer. Growth factors, including insulin-like growth factor (IGF) I and II, regulate the cell cycle in most mammalian tissues. Hence, we measured IGF-I and IGF-II receptor expression in colonocytes from Sprague-Dawley rats fed diets containing either beef tallow (BT) or corn oil (CO) at 12, 30 or 37% of energy for 4 wk. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using an internal standard was used to examine the relative expression of both IGF-I and II receptor mRNA in three sections of the colon. The IGF-I receptor protein was also measured by Western immunoblot. In the distal colon, IGF-I receptor gene expression and protein increased significantly as the percentage of CO increased. In both proximal and middle colon, an increased percentage of BT resulted in significantly increased IGF-II receptor expression. In the proximal colon, IGF-II receptor expression decreased with increasing CO concentration, whereas in the middle colon, rats fed 37% CO had significantly higher IGF-II receptor expression than rats fed 12 or 30% CO. IGF-II receptor gene expression in proximal colon decreased with increased fat quantity, independently of fat source, whereas in the middle colon, increased fat quantity resulted in increased IGF-II receptor expression. Thus IGF-I and IGF-II receptor mRNA and IGF-I receptor protein level in colon mucosa were significantly altered by dietary fat source and quantity, thereby suggesting a potential influence of dietary fat on the endocrine regulation of colon cell mitogenesis.

Brain neutral lipids and phospholipids are modified by long-term feeding of beef tallow vs. corn oil diets.

Previous studies examining the response of brain lipids to dietary fat modification have not quantified neutral lipids such as diacylglycerols (DG) and triacylglycerols (TG). In this study we measured the concentrations of neutral lipids and phospholipids, and their fatty acid profiles, in the cerebra of rats fed defined diets containing either beef tallow (BT) or corn oil (CO) at 12% or 37% of energy. The diets were fed to rat pups beginning at 18 d of age and continued for 31 wk. The proportion of brain linoleic acid [18:2(n-6)] in TG from CO-fed rats was two- to fourfold greater than in BT-fed rats. Although 18:2(n-6) levels were higher in serum and brain TG of rats fed CO, differences in other TG fatty acid concentrations in serum were not reflected in the brain. Rats fed CO diets had higher concentrations of 18:2(n-6) in brain phospholipids as well as neutral lipids compared with rats fed BT diets, and the differences were greater in rats fed 37% rather than 12% of energy as fat. Differences in other polyunsaturated fatty acids associated with dietary fat composition were also found among the brain phospholipids. Most notably, the concentration of docosapentaenoic acid [22:5(n-6)] in brain phospholipids was highest in rats fed diets containing the lowest concentrations of alpha-linolenic acid [18:3(n-3)]. A concentration of 0.1 mg 18:3(n-3)/g diet appeared to be adequate to prevent elevation of 22:5(n-6) in brain phospholipids. These results demonstrate that consumption of a low fat diet (12% of energy) primarily comprised of saturated fats may potentiate an 18:3(n-3) deficiency in brain of rats.

Dietary fat quantity and composition alter colon cell kinetics in growing rats.

The effects of corn oil and beef tallow on the proliferation of colon mucosal cells in rats were investigated. In protocol 1, rats were fed diets containing 12 or 38% kJ from fat supplied by either corn oil or beef tallow. Colon crypt column cell number was examined histologically. The source of dietary fat had no effect on the number of cells per crypt column, but rats fed 38% fat had significantly fewer cells per crypt column in the proximal colon than rats fed 12%. Protocol 2 examined the effects of diets containing corn oil or beef tallow at 12, 30, or 37% kJ on the percentage of colon cells in phases of the cell cycle using flow cytometry and expression of proliferating cell nuclear antigen (PCNA). Rats fed corn oil had more cells in S phase compared to rats fed beef tallow. Rats fed 30 or 37% fat had more cells in G1 and fewer cells in G2 + M compared to rats fed 12%. Animals consuming the 12% corn oil diet or the 37% beef tallow diet had the fewest colon cells expressing PCNA, while those animals consuming the 37% corn oil diet or the 12% beef tallow diet had the greatest number of cells expressing PCNA. Based on combined interpretation of PCNA and cell cycle phases, the results suggest that diets high in saturated fat result in reduced colon cell proliferation whereas diets high in unsaturated fat do not.

Influence of dietary fat quantity and composition on insulin binding to rat intestine.

It is presently recommended that the general US population reduce the consumption of dietary lipid in order to reduce the risk of several chronic diseases, although the mechanism(s) through which dietary factors alter cellular function remain unclear. Dietary lipid composition has been shown to alter the plasma membrane lipid composition of adipocytes, muscle and other tissues. These changes in membrane lipid composition have been correlated with altered insulin receptor binding and signal transduction. Insulin receptors are present on mucosal cells of the intestinal tract, although their role in this tissue is not fully understood. We have fed rats diets containing 6, 31.4 or 76% of calories from lard (Protocol 1) and found insulin binding to be increased in the duodenum and decreased in the colon of rats fed the high-fat diet. Additionally, we compared diets containing either 12 or 37.6% of calories from beef tallow (saturated fatty acids or SFA) or corn oil (polyunsaturated fatty acids or PUFA; Protocol 2) and found insulin binding in the jejunum to be significantly decreased by a low SFA or high PUFA diet relative to the low PUFA diet. These results suggest that intestinal insulin receptors are responsive to dietary lipid quantity and quality which may have implications as to the role of dietary factors in modifying nutrient transport and/or risk of intestinal disease.

An open controlled assessment of osteopathic manipulation in nonspecific low-back pain.

An open controlled pilot trial on nonspecific low-back pain sufferers demonstrated responsiveness to osteopathic manipulation of some patients presenting with pain durations of 14 to 28 days. No response was demonstrated in those with shorter episodes at presentation. The advantage to manipulated patients was maximal between 1 and 2 weeks after commencing treatment, but was not discernable after 4 weeks. The demonstration of a similar responsive stratum by other investigators, with both teams totally unaware of each other's work during data collection, suggests a high degree of reliability for this finding.