Protection of intestinal occludin tight junction protein by dietary gangliosides in lipopolysaccharide-induced acute inflammation.

OBJECTIVES: Intestinal permeability and barrier function are regulated by expression of tight junction proteins. Lipopolysaccharide (LPS), tumor necrosis factor-alpha, and interleukin-1beta induce expression of nitric oxide (NO) and reduce the expression of gut tight junction proteins. The purpose of this study was to determine whether dietary gangliosides (GGs) increase the concentration of the anti-inflammatory cytokine interleukin-10 (IL-10) in response to LPS, thereby inhibiting NO production and protecting gut occludin tight junction protein from degradation. MATERIALS AND METHODS: Rats were fed semipurified diets with (n = 16) or without (n = 16) GGs (0.1% w/w of total lipid). After 2 weeks of feeding, animals were injected with saline (n = 8/diet group) or LPS (n = 8/diet group) (IP, 3 mg mL(-1) kg(-1)). Intestinal tissue, mucosa, and blood sample were collected 6 hours post-LPS exposure. The effect of dietary GGs on production/expression of IL-10, NO, inducible NO synthase, and occludin protein was determined. RESULTS: Dietary GGs increased IL-10 content in intestinal mucosa significantly by 32-fold (P < 0.0001) and in plasma by 2.4-fold (P < 0.001). Feeding animals a ganglioside-enriched diet decreased total NO content in intestinal mucosa and plasma by 44% and 30%, respectively, and inhibited inducible NO synthase expression following LPS exposure compared with control animals. Dietary GGs reduced the degradation of occludin tight junction protein in response to LPS. CONCLUSIONS: Dietary GGs inhibit degradation of gut occludin tight junction protein during LPS-induced acute inflammation. Thus, dietary GGs have a role in protecting the integrity of the intestinal barrier during acute gut inflammation.

Postnatal dietary supplementation with either gangliosides or choline: effects on spatial short-term memory in artificially-reared rats.

This study addressed the hypothesis that dietary supplementation with either gangliosides or choline during the brain growth spurt would enhance short-term spatial memory. Male Long-Evans rats were reared artificially from postnatal days (PD) 5-18 and were fed diets containing either (i) choline chloride 1250 mg/l (CHL), (ii) choline chloride 250 mg/l and GD3 24 mg/l (GNG) or (iii) choline chloride 250 mg/l (STD). A fourth group (SCK) was reared normally. Rats were weaned onto AIN 93G diet and on PD 35 were trained on a cued delayed- matching-to-place version of the Morris water maze. All groups learned to swim to the beacon that indicated the platform position on the first trial; similarly, on the second un-cued trial, the distance swam to reach the platform decreased to the same extent in all groups over the five days of training. The groups also responded in the same way to an increase in delay between the first and second trial from 1 min to 1 h, showing an increase in the distance swam, accompanied by a decrease in the number of direct swims to the platform. Thus, all rats were equally proficient at using spatial short-term memory, regardless of the choline or ganglioside content of the preweaning diet.

Dietary gangliosides increase the content and molecular percentage of ether phospholipids containing 20:4n-6 and 22:6n-3 in weanling rat intestine.

This study was conducted to determine whether dietary ganglioside (GG) increases the content of ether phospholipids (EPL) in intestinal mucosa. Weanling Sprague-Dawley rats were fed a semipurified diet consisting of 20% fat as a control diet. Two experimental diets were formulated by adding either 0.1% (w/w fat) GGs (GG diet) or 1.0% (w/w fat) sphingomyelin (SM diet) to the control diet. Fatty acid methyl esters from the alkenylacyl, alkylacyl and diacyl subclasses of phospholipids were measured to determine total and molecular percentage of EPL comprising the choline phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG) fraction. Animals fed the GG diet significantly increased total EPL content both in CPG (by 36%) and in EPG (by 66%), and the molecular percentage of EPL in CPG (by 76%) and in EPG (by 59%) compared to animals fed the control diet. Dietary GG-induced increase in EPL resulted in a higher level of polyunsaturated fatty acids (PUFA) specifically in 20:4n-6 and 22:6n-3 compared to control animals, leading to a decrease in the ratio of saturated fatty acids (SFA) to PUFA both in CPG and in EPG. Feeding animals the SM diet showed a higher level of EPL than control animals with a concomitant increase in 22:6n-3 in EPL. The present data demonstrate that dietary GG increases the content and composition of EPL containing PUFA in the weanling rat intestine.

Fatty acid composition of serum phospholipid of premenopausal women and postmenopausal women receiving and not receiving hormone replacement therapy.

OBJECTIVE: To compare the fatty acid composition of serum phospholipid of premenopausal women with that of postmenopausal women receiving and not receiving hormone replacement therapy (HRT). DESIGN: Women between the ages of 43 and 70 were recruited for two separate case-comparison studies. Participants were grouped as either premenopausal, postmenopausal receiving HRT, or postmenopausal not receiving HRT. All participants were required to complete a 3-day dietary record before providing a 12-h fasting blood sample. Fatty acid composition of phospholipids and lipid concentrations was determined from serum samples. RESULTS: The postmenopausal women receiving HRT had significantly higher concentrations of palmitic acid (16:0), palmitoleic acid (16:1), and di-homo-gamma-linolenic (20:3n-6) and significantly lower levels of docosapentaenoic acid (22:5n-3) than the other groups in both studies. In addition, the postmenopausal women receiving HRT had lower levels of behenic (22:0), lignoceric (24:0), and nervonic acid (24:1) in comparison with the postmenopausal women not receiving HRT. CONCLUSION: The results of this study indicate that the fatty acid composition of serum phospholipids in women is influenced by menopausal status and hormone use. These results are of interest because high levels of 20:3n-6 and low levels of docosapentaenoic acid have been associated with increased myocardial infarction plus stroke mortality from cardiovascular disease.

Fatty acid compositions of serum phospholipids of postmenopausal women: a comparison between Greenland Inuit and Canadians before and after supplementation with fish oil.

OBJECTIVES: We compared serum phospholipid fatty acid compositions, in particular the status of omega-3 polyunsaturated fatty acid (PUFA), of postmenopausal Greenland Inuit women and postmenopausal Canadian women at baseline and after supplementing the Canadian women with a fish-oil product. METHODS: Fasting serum samples were collected from 15 Inuit subjects from Greenland and 16 non-Inuit subjects from Canada. In addition, eight Canadian subjects provided fasting serum samples after completing a long-chain omega-3 PUFA intervention (2.4 g of eicosapentaenoic acid [EPA] plus 1.6 g of docosahexaenoic acid [DHA] per day) for 28 d. Fatty acid compositions of serum phospholipids of the samples were determined and compared by one-way analysis of variance. RESULTS: In comparison with the Greenlanders, baseline Canadian women had 73% and 46% less EPA (20:5omega-3) and DHA (22:6omega-3), respectively, and 32% and 91% more linoleic acid (LA; 18:2omega-6) and arachidonic acid (AA; 20:4omega-6), respectively. The omega-3 supplementation in Canadian women increased DHA and decreased LA levels to approach those in Greenland Inuit and raised EPA levels to surpass (45% higher) those in Greenland women (P < 0.0001). In contrast, AA was only moderately lowered (by 16% overall) such that AA levels remained 62% higher in the supplemented Canadians than in the Greenlanders (P < 0.0001). CONCLUSIONS: Short-term EPA plus DHA supplementation of postmenopausal North American women can mimic the high EPA and DHA levels and lower LA levels in corresponding Inuit women but not the markedly lower levels of AA. The present findings also support the hypothesis of genetically decreased Delta5-desaturase potential in the Greenland Inuit compared with Canadian postmenopausal women.