Miyoung Suh

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.

Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol)

Using streptozotocin-induced diabetic Wistar rats, studies were carried out to examine the metabolic availability of vitamin A in the plasma, liver and the retina of the eye. Control and diabetic rats were fed ad lib. on a semi-purified diet either with or without (basal) vitamin A supplementation, or pair-fed on the basal diet for 4 weeks. Despite the fact that diabetic rats consumed 48% more feed, they had lower plasma concentrations of retinol (P < 0.003). The decrease in plasma retinol concentration was a response to diabetes (or diabetes-induced trauma), since neither pair-feeding (P < 0.01) nor vitamin A supplementation altered this effect (P < 0.05). Furthermore, the hepatic concentrations of the vitamin in these animals remained elevated and this increase was greater in the supplemented diabetic group (P < 0.001). Decreases in 11-cis retinal (a component of rhodopsin) concentrations in the retina were also observed in diabetic animals. The increased hepatic and the decreased plasma and retina vitamin A levels suggest a defect in the transport of the vitamin from the liver.

Dietary fat alters membrane composition in rod outer segments in normal and diabetic rats: Impact on content of very-long-chain (C ⩾ 24) polyenoic fatty acids

The effect of high n - 3 (5.8%, w/w) vs. a low n - 3 (1.2%, w/w) fatty acids in a diet with a low ratio of polyunsaturated/saturated fatty acids (P/S = 0.27) content was investigated to determine the effect of diet on the level of long- and very-long-chain fatty acids (VLCFA C > or = 24) in phospholipids of rod outer segments (ROS) of normal and diabetic rats. After 6 weeks of feeding, diets high in n - 3 fatty acids increased the levels of 22:5(n - 3) and 22:6(n - 3), while decreasing the 22:5(n - 6) level in all major phospholipid classes. n - 6 and n - 3 VLCFA of C24 to C34 with 4, 5 and 6 double bonds were found only in phosphatidylcholine (PC) while other phospholipid classes contained only C24 fatty acids as minor components. The content of VLCFA in PC was approx. 6.7% (w/w) of total fatty acids in the ROS. Feeding a high n - 3 fatty acid diet significantly reduced n - 6 tetraenoic VLCFA in all phospholipids. In the diabetic state, the levels of n - 6 tetraenes and pentaenes in individual phospholipids were different from control animals. This study demonstrates that the VLCFA content of photoreceptor cells reflects the dietary level of n - 3 fatty acids fed. The unique polyenoic n - 6 and n - 3 VLCFA appear to be synthesized from shorter chain precursors which respond to altering the ratio of n - 6/n - 3 fatty acids fed.

Dietary lipids containing gangliosides reduce Giardia muris infection in vivo and survival of Giardia lamblia trophozoites in vitro.

We examined whether a ganglioside supplemented diet affected the course of Giardia muris infection in mice and survival of Giardia lamblia trophozoites in vitro. Female CD-1 mice were fed 1 of 5 experimental diets: standard lab chow as a control diet; semi-synthetic diets containing 20% (w/w) triglyceride based on the fat composition of a conventional infant formula; triglyceride diet; triglyceride diet containing a low level of ganglioside (0.1% w/w); and triglyceride diet containing a high level of ganglioside (1.0% w/w of diet). After 2 weeks of feeding, mice were inoculated with G. muris by gastric intubation and fed the experimental diets during the course of the infection. Cysts released in the faeces and trophozoites present in the small intestine were enumerated at various times post-infection. The average cyst output and the number of trophozoites during the course of the infection in mice fed ganglioside-containing diet were found to be significantly lower (3-log10 reduction) compared to animals fed control diets. The results of in vitro growth studies indicated that gangliosides may be directly toxic to the parasites. Thus, gangliosides have a protective effect against G. muris infection in vivo and affect the survival of G. lamblia trophozoites in vitro.

Relationship between dietary supply of long-chain fatty acids and membrane composition of long- and very long chain essential fatty acids in developing rat photoreceptors

The present study was designed to determine if dietary supply of long-chain fatty acid (LCFA, C20∶4n-6, and/or C22∶6n-3), reflecting levels that might be incorporated into infant formulas, influences the fatty acid composition of the visual cell membrane. The rod outer segment (ROS) of the retina was analyzed from rats fed diets varying in the ratio of 18∶2n-6 to 18∶3n-3 with or without 20∶4n-6 [arachidonic acid (AA)] and 22∶6n-3 (docosahexaenoic acid) from birth to six weeks of age. The level of very long chain fatty acids (VLCFA, C24−C36) was identified using gas chromatography and gas chromatography-mass spectrometry. In the ROS, the highest relative percent of AA was attained in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of animals fed 1% AA diet, whereas feeding 0.7% docosahexaenoic acid (DHA) diet significantly increased the DHA level in PC, phosphatidylserine, and phosphatidylinositol compared to feeding diets containing AA. VLCFA of n-6 and n-3 up to C36 were found in PC, with the most abundant fatty acids being C32 and C34. In PC, phosphatidylserine and PE, the n-6 tetraenoic VLCFA level was highly increased in animals fed 1% AA compared to other dietary groups. This study suggests that dietary fat containing small amounts of AA or DHA is an important factor influencing membrane fatty acid composition of the visual cell during development.

Dietary n-3 FA modulate long and very long chain FA content, rhodopsin content, and rhodopsin phosphorylation in rat rod outer segment after light exposure.

A previous study has shown that the long and very long chain FA (VLCFA) content of the rat retina responds to changes in dietary n−6/n−3 ratio of the fat fed (1). The present study tested whether similar changes in these FA are associated with alterations in rhodopsin content and rhodopsin phosphorylation after light treatment. Weanling rats were fed diets containing 20% (w/w, 40% energy) fat with either high (4.8%, w/w) or low (1.2%, w/w) n−3 FA. After 6 wk of feeding, half of the animals in each group were exposed to light for 48 h at 350 lx or were kept in complete darkness. In the rod outer segment, the high n−3 diet treatment increased the level of 20∶5n−3 and 22∶6n−3 and reduced the levels of 20∶4n−6 and 24∶4n−6 in PC, PE, and PS. After the feeding of a high n−3 FA diet, total n−3 pentaenoic VLCFA from C24 to C34 increased in PC, whereas the n−6 tetra- and pentaenoic VLCFA decreased. No changes occurred in n−3 hexaenoic VLCFA regardless of the level of 22∶6n−3 in the diet. After light exposure, animals fed a high n−3 FA diet showed reduction in 22∶6n−3 as well as in n−6 and n−3 VLCFA in PC. FFA and TG fractions contained increased levels of both 20∶4n−6 and 22∶6n−3 after light exposure. Dark-adapted rhodopsin content and rhodopsin phosphorylation in the rod outer segment of rats fed the low n−3 FA diet were higher than in animals fed a high n−3 FA diet. After light exposure, animals fed the low n−3 FA diet lost more rhodopsin compared to animals fed the high n−3 FA diet, resulting in less phosphorylation of rhodopsin. Results indicate that the FA composition, rhodopsin content, and phosphorylation in visual cells is influenced by the dietary n−3 FA fed as well as by light exposure. The results also imply that 22∶6n−3 may not be the precursor for synthesis of hexaenoic VLCFA.

Impact of Dietary Essential Fatty Acids on Neuronal Structure and Function

The form of nervous system brain development at early stages is remarkably similar in adult vertebrates. Distinct characteristics of the neural plate and neural tube, from which the nervous system originates in all vertebrates, suggests that development of the central nervous system occurs through similar overall mechanisms. Cells, regions, and various brain structures do not develop uniformly as in other tissues and organs (Dobbing, 1990; Dobbing & Sands, 1979; Herschkowitz, 1989). Well-defined stages of growth occur anatomically and biochemically (Albers, 1985; Gottlieb et al., 1977) and result in significant growth spurts of critical periods during fetal and neonatal life. Brain development occurs in stages: induction of the neural plate, localized proliferation of cells in different regions, migration of cells, formation of identifiable parts of the brain by cell aggregation, differentiation of immature neurons, formation of connections, selective cell death, and modification of connections (Cowan, 1979). These changes within the developing nervous system proceed in a caudal (brainstem) to rostral sequence (Jacobson, 1970). Caudal brain structures include phylogenetically older brain structures, whereas rostral structures are phylogenetically more recent (McLean, 1970). Brain development results in increase in weight and size that is not necessarily parallel: The greatest growth in size occurs prior to the greatest gain in weight (Marshall, 1968). Different parts of the brain grow at different speeds and not all regions reach their fastest rates at the same time. In this respect, the “growth spurt” and velocity curves as defined by Dobbing (Dobbing & Sands, 1979; Dobbing, 1968, 1971) represent rates of change in total brain weight over time and not individual regions of the brain. The early concepts developed by Dobbing did not encompass other developmental processes that are now also understood to be critical periods of growth and highly susceptible to nutritional insult or reflect interrelationships of growth occurring in subregions of the developing brain (Morgane et al., 1993).