M.T. Clandinin

Relationship between fatty acid accretion, membrane composition, and biologic functions.

Dietary fat affects metabolic pathways for phospholipid biosynthesis in tissues in a coordinated fashion. This may be important to aspects of development that concern phosphatidylcholine metabolism or regulatory processes that depend on signals from a changing milieu in the microenvironment of the membrane. Dietary fat influences the phosphatidylethanolamine (PE) composition in many membranes of the brain and retina and may by altered by small changes in the content of 20:4(6) and 22:6(3). Membrane PE fatty acids that contain one, four, or six double bonds and the ratio of 22:5(6) to 22:6(3) in PE that contains four to six double bonds are also affected. An increase in the omega 6 fatty acid content of membranes is associated with increased PE methyltransferase activity and decreased phosphocholine transferase activity, thus indicating a mechanism by which change in an exogenous factor (e.g., dietary fat intake) may alter neural phospholipid biosynthesis. Small changes in the composition of dietary fat intake change the composition of brain membranes during development. It is provocative to ponder whether diet could be used to induce formation of membrane structures that are more resistant to specific insults that cause degeneration of brain structural material, to ensure optimal functional compositions, or to reverse degenerative changes that occur in neural membrane structure and function.

Recent advances in celiac disease

Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists.

Dietary ganglioside inhibits acute inflammatory signals in intestinal mucosa and blood induced by systemic inflammation of Escherichia coli lipopolysaccharide.

Our previous study demonstrated that feeding ganglioside increased total ganglioside content while decreasing cholesterol and caveolin-1 content in developing rat intestinal lipid microdomains. Cholesterol or caveolin depletion in membranes inhibits inflammatory signaling by disrupting microdomain structure. We hypothesized that dietary ganglioside-induced reduction in cholesterol content will reduce proinflammatory mediators in the intestinal mucosa after acute exposure to bacterial endotoxin. Weanling rats were fed semipurified diets with 0.1% (wt/wt of total fat) gangliosides (treatment) or without ganglioside (control). After 2 weeks of feeding, half of animals from each diet group were injected with saline or lipopolysaccharide (LPS) endotoxin (Escherichia coli serotype O111:B4, intraperitoneal, 3 mg/kg body weight) to induce acute gut inflammation. Intestinal mucosa and blood were collected after 6 h. The effect of dietary ganglioside on proinflammatory mediators including cholesterol, platelet-activating factor, prostaglandin E2, leukotriene B4 (LTB4), interleukin-1&bgr; (IL-1&bgr;), and tumor necrosis factor-&agr; (TNF-&agr;) was determined in inflamed mucosa and blood. Feeding animals the control diet increased cholesterol content in intestinal lipid microdomains by 92% after LPS injection compared with saline injection. Animals fed the ganglioside diet significantly decreased cholesterol content in lipid microdomains by 60% compared with animals fed the control diet. Feeding animals the ganglioside diet increased total ganglioside content by 90% while decreasing platelet-activating factor content by 45% in the inflamed mucosa by acute systemic exposure to LPS compared with animals fed the control diet. When animals were fed the ganglioside diet, the levels of prostaglandin E2, LTB4, IL-1&bgr;, and TNF-&agr; were lower in inflamed mucosa, and LTB4, IL-1&bgr;, and TNF-&agr; were decreased in plasma by 41%, 58%, and 55% compared with control animals, respectively. The present study demonstrates that dietary gangliosides inhibit proinflammatory signals in the intestine and blood induced by acute inflammation of LPS and suggests therapeutic potential in the treatment and management of acute local and systemic inflammatory diseases.

The age-related decline in intestinal lipid uptake is associated with a reduced abundance of fatty acid-binding protein

Aging is associated with changes in the absorptive capacity of the small intestine. We tested the hypotheses that (i) aging is associated with a decline in lipid absorption, and that (ii) this decreased lipid absorption is due to a decline in the abundance of mRNA and/or the enterocyte cytosolic intestinal FA-binding protein (I-FABP), the liver FA-binding protein (L-FABP), and the ileal lipid-binding protein (ILBP). In vitro uptake studies were performed on Fischer 344 rats at ages 1, 9, and 24 mon. Northern blotting (L-FABP, ILBP) and immunohistochemistry (I-FABP, ILBP) were performed. Aging was associated with decreased animal weights, but the surface area of the intestine was not significantly altered with age. The rates of ileal uptake of 16∶0, 18∶0, 18∶1, and 18∶2 were reduced by greater than 50% with aging when expressed on the basis of mucosal weight. This decline was not associated with reduced expression of mRNA for L-FABP or ILBP but was associated with a 50% decrease in the abundance of I-FABP and a 40% decrease in the abundance of ILBP. Thus, the decrease with aging in the ileal uptake of some FA when rates were expressed on the basis of mucosal weight was associated with a reduced abundance of I-FABP and ILBP.

Locally and systemically active glucocorticosteroids modify intestinal absorption of lipids in rats.

Orally administered systemically active steroids enhance the digestive and absorptive functions of the intestine, but their effect on lipid uptake is unknown. The effect of the locally acting steroid budesonide on intestinal absorptive function also is unknown. Accordingly, this study was undertaken to assess the influence of 4 wk of treatment of weaning male rats with a daily oral gavage of budesonide (BUD), prednisone (PRED), or control vehicle on the jejunal and ileal uptake of fatty acids and cholesterol. BUD enhanced jejunal uptake of oleic acid and ileal uptake of linoleic acid. PREF increased jejunal uptake of cholesterol and ileal uptake of lauric, palmitic, linoleic, and linolenic acids. Higher doses of BUD (up to 1 mg/kg) given to adult rats for 2 wk further increased the uptake of some lipids. The changes in the uptake of lipids were not due to variations in the weight of the intestinal mucosa or in the animals’ food intake. Ileal ornithine decarboxylase mRNA expression was increased with PRED, but there were no steroid-associated changes in the expression of the mRNA of the early response genes c-myc, c-jun, or c-fos or of proglucagon, the liver fatty acid-binding protein (FABP), the ileal lipid-binding protein, tumor necrosis factor α, interleukin 2 (IL-2), IL-6, or IL-10. In summary, treatment of weanling rats with BUD and DRED enhances the uptake of some lipids by a process that is independent of the effects of early response genes and genes encoding cytokines, proglucagon, and FABP.

Recent advances in small bowel diseases: Part I

As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Partu2005Iu2005of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician.

An isocaloric PUFA diet enhances lipid uptake and weight gain in aging rats

Aging is associated with a change in the morphology and absorptive capacity of the small intestine. In young rats, feeding a semisynthetic diet containing saturated FA (SFA) increases nutrient uptake, as compared with an isocaloric diet containing polyunsaturated FA (PUFA). We tested the hypotheses that (i) aging is associated with a decline in lipid absorption in the Fischer 344 rat; (ii) this decline can be corrected by manipulating the fat composition of the diet; and (iii) the age-and diet-associated variations in lipid uptake are associated with changes in the ileal lipid-binding protein (ILBP) or the intestinal or liver FA-binding proteins (l-or L-FABP, respectively) in the cytosol of the enterocyte. In rats fed SFA or PUFA, aging was associated with a decline in the in vitro uptake of stearic acid (18∶0) when expressed on the basis of intestinal or mucosal weight. In contrast, age had no effect on lipid uptake when expressed on the basis of serosal surface area, whereas lipid uptake increased with age when expressed on the basis of mucosal surface area. The age-associated variations in lipid uptake were not associated with changes in protein abundance and/or expression of ILBP, I-FABP, or L-FABP. In 24-mon-old rats, when uptake of lipids was expressed on the basis of mucosal surface area, feeding PUFA enhanced lipid uptake and body weight gain as compared with rats fed SFA. Future studies must determine whether the enhanced lipid uptake and body weight gain observed in older animals fed PUFA have any therapeutic benefit.

Aging of the Gastrointestinal System

All multicellular organisms undergo change with time. This concept of aging may be considered in different ways. The maximum life span and the average life span are two commonly used definitions. The process of aging must take into account social, biological, physiological, emotional, socioeconomic, as well as cellular and molecular changes. Aging is a multifactorial conditional with environmental and genetic factors. While chronological age is easy to measure, biological age is a better marker of health status that allows for the concept of the introduction of processes to ameliorate the aging process, thereby compressing morbidity, improving competence, well being, and quality of life [1].