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Biomedical subjects

M L Garg

Publications and source records attributed to M L Garg.

At least 55 records · Page 3Linked to original sources

Influence of dietary fat composition on intestinal absorption in the rat.

Omega-3 fatty acids influence the function of the intestinal brush border membrane. For example, the omega-3 fatty acid eicosapentaenoic acid (20:5 omega 3) has an antiabsorptive effect on jejunal uptake of glucose. This study was undertaken to determine whether the effect of feeding alpha-linolenic acid (18:3 omega 3) or EPA plus docosahexaenoic acid (22:6 omega 3) on intestinal absorption of nutrients was influenced by the major source of dietary lipid, hydrogenated beef tallow or safflower oil. The in vitro intestinal uptake of glucose, fatty acids and cholesterol was examined in rats fed isocaloric diets for 2 weeks: beef tallow, beef tallow + linolenic acid, beef tallow + eicosapentaenoic acid/docosahexaenoic acid, safflower oil, safflower oil + linolenic acid, or safflower oil + eicosapentaenoic acid/docosahexaenoic acid. Eicosapentaenoic acid/docosahexaenoic acid reduced jejunal uptake of 10 and 20 mM glucose only when fed with beef tallow, and not when fed with safflower oil. Linolenic acid had no effect on glucose uptake, regardless of whether it was fed with beef tallow or safflower oil. The jejunal uptake a long-chain fatty acids (18:0, 18:2 omega 6, 18:3 omega 3, 20:4 omega 6, 20:5 omega 3 and 22:6 omega 3) and cholesterol was lower in safflower oil than with beef tallow. When eicosapentaenoic acid/docosahexaenoic acid was given with beef tallow (but not with safflower oil), there was lower uptake of 18:0, 20:5 omega 3 and cholesterol. The demonstration of the inhibitory effect of linolenic acid or eicosapentaenoic acid/docosahexaenoic acid on cholesterol uptake required the feeding of a saturated fatty acid diet (beef tallow).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fish oil prevents change in arachidonic acid and cholesterol content in rat caused by dietary cholesterol.

Rats were fed diets high in either saturated fat (beef tallow) or alpha-linolenic acid (linseed oil) or eicosapentaenoic and docosahexaenoic acids (fish oil) with or without 2% cholesterol supplementation. Consumption of linseed oil and fish oil diets for 28 days lowered arachidonic acid content of plasma, liver and heart phospholipids. Addition of 2% cholesterol to diets containing beef tallow or linseed oil lowered 20:4 omega 6 levels but failed to reduce 20:4 omega 6 levels when fed in combination with fish oil. Feeding omega 3 fatty acids lowered plasma cholesterol levels. Addition of 2% cholesterol to the beef tallow or linseed oil diet increased plasma cholesterol concentrations but not when fish oil was fed. Feeding the fish oil diet reduced the cholesterol content of liver, whereas feeding the linseed oil diet did not. Dietary cholesterol supplementation elevated the cholesterol concentration in liver in the order: linseed oil greater than beef tallow greater than fish oil (8.6-, 5.5-, 2.6-fold, respectively). Feeding fish oil and cholesterol apparently reduced 20:4 omega 6 levels in plasma and tissue lipids. Fish oil accentuates the 20:4 omega 6 lowering effect of dietary cholesterol and appears to prevent accumulation of cholesterol in plasma and tissue lipids under a high dietary load of cholesterol.

Animals↗

Dietary saturated fat level alters the competition between alpha-linolenic and linoleic acid.

Male weanling rats were fed semi-synthetic diets high in saturated fat (beef tallow) vs high in linoleic acid (safflower oil) with or without high levels of alpha-linolenic acid (linseed oil) for a period of 28 days. The effect of feeding these diets on cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding linseed oil with beef tallow or safflower oil had no significant effect on serum levels of cholesterol. Serum cholesterol concentration was higher in animals fed the safflower oil diet than in animals fed the beef tallow diet without linseed oil. Feeding linseed oil lowered the cholesterol content in liver tissue for all dietary treatments tested. Consumption of linseed oil reduced the arachidonic acid content with concomitant increase in linoleic acid in serum and liver lipid fractions only when fed in combination with beef tallow, but not when fed with safflower oil. Similarly, omega 3 fatty acids (18:3 omega 3, 20:5 omega 3, 22:5 omega 3, 22:6 omega 3) replaced omega 6 fatty acids (20:4 omega 6, 22:4 omega 6, 22:5 omega 6) in serum and liver lipid fractions to a greater extent when linseed oil was fed with beef tallow than with safflower oil. The results suggest that the dietary ratio of linoleic acid to saturated fatty acids or of 18:3 omega 3 to 18:2 omega 6 may be important to determine the cholesterol and arachidonic acid lowering effect of dietary alpha-linolenic acid.

Animals↗

Intestinal aspects of lipid absorption: in review.

The rapidly evolving field of lipid absorption is reviewed with the thrust of new knowledge focused on the interpendency of the luminal and cellular phases of absorption. To date little attention has been paid to factors that regulate the phospholipid biosynthesis in the enterocyte. The availability of 20:4 omega 6 may be the rate-limiting factor for phospholipid synthesis. The source of 20:4 omega 6 is unknown, whether it be synthesized de novo the enterocyte or entirely originating from degradation of bile phospholipid. It has been established that dietary fat can modulate the enterocyte membrane lipid composition and transport properties. Specified fats such as as fish oils rich in 20:5 omega 3 and 22:6 omega 3 have been implicated as protective against hypercholesterolemia. However, the effects of these dietary fats on the transport of nutrients across the enterocyte are not yet known, nor are the mechanisms responsible for the adaptive responses of the brush border identified.

Animals↗

Fish oil prevents effect of high cholesterol diet on active intestinal transport of galactose.

We tested the hypothesis that diets containing fish oils prevent the effects of a high cholesterol diet on the morphology and nutrient uptake of the intestine. Isocaloric semisynthetic diets were supplemented with beef tallow or fish oil containing low or high amounts of cholesterol and were fed to growing female Wistar rats for 14 days, after which the in vitro jejunal and ileal uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined. Feeding cholesterol with beef tallow was associated with a 12% decrease in the jejunal mucosal surface area. Feeding fish oil decreased jejunal mucosal surface area by 24%, as compared with the beef tallow diet, but the reduction was increased to 42% when fish oil and cholesterol were fed together. Ileal surface area was unaffected by varying the major source of dietary lipid, or by adding cholesterol. Despite the effect of fish oil on the mucosal surface area, the jejunal and ileal uptake of saturated as well as unsaturated long-chain fatty acids and cholesterol was similar in the four diet groups. Cholesterol supplementation enhanced the jejunal uptake of high concentrations of galactose only when fed with beef tallow, i.e., feeding fish oil prevented the enhancing effect of cholesterol on galactose uptake observed when beef tallow was fed. Thus, (i) a fish oil diet prevents the enhancing effect of cholesterol on jejunal active transport of galactose, an effect not explained by the reduction in jejunal mucosal surface area observed with the fish oil diet; (ii) these dietary manipulations result in a clear dissociation of the morphological from the transport adaptation of the intestine; and (iii) substitution of fish oil for beef tallow as the major source of lipid in the diet prevents the influence of cholesterol on the active intestinal transport of galactose.

Animals↗

Dietary cholesterol and/or n-3 fatty acid modulate delta 9-desaturase activity in rat liver microsomes.

delta 9-Desaturase activity and fatty acid composition of liver microsomal phospholipids in rats fed diets enriched with either saturated (hydrogenated beef tallow) or alpha-linolenic (linseed oil) or eicosapentaenoic and docosahexaenoic (fish oil) acids with or without 2% cholesterol supplementation were investigated. Both the linseed oil and the fish oil diets inhibited delta 9-desaturase activity in the rat liver microsomes. The inhibition was greater when feeding fish oil (90%) compared with the linseed oil (60%) diet. Dietary cholesterol feeding accelerated conversion of palmitic (16:0) to palmitoleic (16:1) acid, irrespective of the fatty acid supplement. Feeding the linseed oil diet decreased, while feeding the fish oil diet increased synthesis of the monounsaturated fatty acids of n-7 series (palmitoleic and vaccenic acid) and decreased 18:1(n-9) in microsomal membrane lipids when compared with animals fed beef tallow. Addition of 2% cholesterol to the otherwise low cholesterol diets led to accumulation of 16:1(n-7), and 18:1(n-9) in microsomal membranes. These results suggest that delta 9-desaturase activity is dependent on the cholesterol contents as well as the n-3 fatty acid content of microsomal membranes on which it is localized.

Animals↗

Fish oil reduces cholesterol and arachidonic acid content more efficiently in rats fed diets containing low linoleic acid to saturated fatty acid ratios.

Rats were fed diets containing a high level of saturated fatty acids (hydrogenated beef tallow) versus a high level of linoleic acid (safflower oil) at both low and high levels of fish oil containing 7.5% (w/w) eicosapentaenoic and 2.5% (w/w) docosahexaenoic acids for a period of 28 days. The effect of feeding these diets on the cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding diets high in fish oil with safflower oil decreased the cholesterol content of rat serum, whereas feeding fish oil had no significant effect on the cholesterol content of serum when fed in combination with saturated fatty acids. The serum cholesterol level was higher in animals fed safflower oil compared to animals fed saturated fat without fish oil. Consumption of fish oil lowered the cholesterol content of liver tissue regardless of the dietary fat fed. Feeding diets containing fish oil reduced the arachidonic acid content of rat serum and liver lipid fractions, the decrease being more pronounced when fish oil was fed in combination with hydrogenated beef tallow than with safflower oil. These results suggest that dietary n-3 fatty acids of fish oil interact with dietary linoleic acid and saturated fatty acids differently to modulate enzymes of cholesterol and fatty acid metabolism.

Animals↗

Homoeostatic control of membrane cholesterol and fatty acid metabolism in the rat liver.

Experiments were designed to assess the effect of cholesterol feeding, with or without high levels of either saturated (coconut oil) or unsaturated (sunflower-seed oil) fat on the fatty acid composition of hepatic microsomal membrane lipids, as well as on the activities of several membrane-bound enzymes of cholesterol synthesis and metabolism. Administration of 2% (w/w) cholesterol in the rat diet inhibited hydroxymethylglutaryl-CoA reductase activity, and this inhibition was much more pronounced when cholesterol was fed in combination with unsaturated rather than with saturated fat. Cholesterol 7 alpha-hydroxylase activity was increased by all the high-cholesterol diets and inhibited by both the high-fat diets. Cholesterol esterification, as assessed by acyl-CoA:cholesterol acyltransferase (ACAT) activity, was enhanced after unsaturated-fat feeding. Cholesterol supplement, without any added fat, failed to elicit any significant increase in ACAT activity, whereas consumption of cholesterol in combination with unsaturated fat led to the greatest increase in ACAT activity. After cholesterol feeding, C18:1 and C18:2 fatty acids in the microsomal phospholipids were increased, with concomitant decreases in C18:0, C20:4 and C22:6 fatty acids, leading to an overall decrease in membrane unsaturation, irrespective of the particular fat supplement. It can be concluded that the inhibition of cholesterol biosynthesis and the enhancement of cholesterol utilization, either by increased bile formation or by increased cholesterol esterification, after cholesterol feeding, may not be enough to prevent cholesterol accumulation in the microsomal membranes. Then, to compensate for the altered fluidity resulting from cholesterol enrichment, the unsaturation of membrane phospholipids is decreased, which would in turn have an effect on membrane lipid fluidity opposite to that of increased cholesterol.

Animals↗

Fatty acid desaturation in the intestinal mucosa.

Information as to the ability of the enterocyte to desaturate fatty acids is lacking. This is important in understanding whether the source of intestinal arachidonic (20:4(n-6) acid is biliary or from de novo synthesis. Delta 9- and delta 6-desaturase enzymes were assayed in homogenates of rat jejunum, ileum and liver. Rat small intestine possesses desaturase activity to convert palmitic (16:0) to palmitoleic (16:1) and linoleic (18:2(n-6) to linolenic (18:3(n-6) acid. Enzyme activities were highest in liver relative to activity in jejunal and ileal homogenates. It is concluded that delta 9- and delta 6-desaturase activities may have an important role in determining physico-chemical properties and thus transport properties of enterocyte membranes.

Animals↗

Delta 6-desaturase activity in liver microsomes of rats fed diets enriched with cholesterol and/or omega 3 fatty acids.

The effect of feeding semipurified diets enriched in linseed (rich in C18:3, omega 3 fatty acid) or fish (rich in C20:5, omega 3 and C22:6, omega 3 fatty acid) oil with and without cholesterol supplementation on the desaturation of linoleic acid (C18:2, omega 6) by rat liver microsomal fractions was investigated. Animals fed diets supplemented with beef tallow were used as equal-energy controls. Both linseed-oil and fish-oil diets, without added cholesterol, decrease conversion of C18:2, omega 6 fatty acid to gamma-linolenic acid (C18:3, omega 6). Reduction in delta 6-desaturation was significantly greater for animals fed the diet containing fish oil than with animals fed the linseed-oil diet. The major effect of cholesterol supplementation was to decrease the rate of desaturation of C18:2, omega 6, when fed in combination with the beef-tallow diet, whereas delta 6-desaturation was unaffected when cholesterol was fed along with diets high in omega 3 fatty acids (linseed oil or fish oil). The activity of the delta 6-desaturase in vitro is consistent with the fatty acid composition observed for the microsomal membranes on which this enzyme is localized. Dietary linseed oil and fish oil lowered the arachidonic (C20:4, omega 6) acid content of rat liver microsomes, with an accompanying increase in membrane eicosapentaenoic (C20:5, omega 3) and docosahexaenoic (C22:6, omega 3) acid content, in comparison with the group fed beef tallow. Inclusion of cholesterol into the beef-tallow or linseed-oil diets resulted in decreased membrane C20:4, omega 6-fatty-acid content, with concomitant increase in C18:2, omega 6-fatty-acid content. However, addition of cholesterol to the fish-oil diet did not alter the microsomal membrane content of C20:4, omega 6 fatty acid. Thus it is suggested that (1) the decrease in prostaglandin E2, thromboxane and prostacyclin levels generally observed after fish-oil consumption may be at least partly due to inhibition of C20:4, omega 6-fatty-acid synthesis from C18:2, omega 6 fatty acid; and (2) consumption of fish oil prevents the further decrease in C20:4, omega 6-fatty-acid levels by dietary cholesterol that is apparent when cholesterol is fed in combination with diets high in saturated fat or C18:3, omega 3 fatty acid.

Animals↗

Differential effects of dietary linoleic and alpha-linolenic acid on lipid metabolism in rat tissues.

Comparative effects of feeding dietary linoleic (safflower oil) and alpha-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased alpha-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18:2 omega 6 shifts cholesterol from plasma to liver pools followed by redistribution of 20:4 omega 6 from tissue to plasma pools. This redistribution pattern was not apparent when 18:3 omega 3 was included in the diet.

Adipose Tissue↗

Effect of dietary cholesterol and/or omega 3 fatty acids on lipid composition and delta 5-desaturase activity of rat liver microsomes.

Male weanling rats were fed for 28 d a purified diet containing 20% (wt/wt) fat providing high levels of either saturated fat or alpha-linolenic acid or eicosapentaenoic and docosahexaenoic acids with or without 2% (wt/wt) cholesterol supplementation. Effect of diet on rate of desaturation of eicosatrienoic acid (20:3 omega 6) and lipid composition of liver microsomal membranes was examined. The desaturation of 20:3 omega 6 to arachidonic acid (20:4 omega 6) was higher in rats fed linseed oil and lower in rats fed fish oil than in control animals fed the beef tallow diet. The desaturation of 20:3 omega 6 was lower in rats fed beef tallow or linseed oil diets supplemented with cholesterol than in the respective unsupplemented diet. Inclusion of 2% (wt/wt) cholesterol in the fish oil diet failed to affect synthesis of 20:4 omega 6 from 20:3 omega 6. These in vitro changes in delta 5-desaturase activity are consistent with the diet-induced alterations observed in the fatty acid composition of microsomal membranes. Both free cholesterol and cholesterol ester in the microsomal membrane were higher in rats fed beef tallow or linseed oil diets supplemented with exogenous cholesterol than in the respective unsupplemented diet, and only free cholesterol was higher in rats fed the fish oil diet supplemented with cholesterol. Feeding fish oil appears to prevent both the inhibition of 20:4 omega 6 biosynthesis and the accumulation of cholesterol ester that were apparent when 2% cholesterol was added to either beef tallow or linseed oil diets.

8,11,14-Eicosatrienoic Acid↗

Regional differences in lipid composition and incorporation of saturated and unsaturated fatty acids into microsomal membranes of rat small intestine.

Incorporation of [1-14C]palmitic (16:0) and [1-14C]linoleic (18:2 omega 6) acids into microsomal membranes of proximal (jejunum) and distal (ileum) regions of rat small intestine was investigated, and the lipid composition, including fatty acid profiles of membrane phospholipids, was determined. Jejunal microsomes contained significantly higher amounts of total phospholipids, phosphatidylcholine, and phosphatidylinositol, and lower amounts of cholesterol and sphingomyelin when compared with ileal microsomes. Jejunal microsomal phospholipids contained higher levels of stearic (18:0), 18:2 omega 6, and eicosapentaenoic (20:5 omega 3) acids followed by reduced levels of oleic (18:1 omega 9), arachidonic (20:4 omega 6), and docosahexaenoic (22:6 omega 3) acids when compared with those from the ileum, except for phosphatidylinositol where no significant difference between 20:4 omega 6 content of each site was observed. In both jejunal and ileal microsomes, incorporation of [1-14C]18:2 omega 6 was significantly higher than that of [1-14C]16:0. Incorporation of both [1-14C]16:0 and [1-14C]18:2 omega 6 was significantly higher in jejunal microsomal lipid fractions (phospholipids, diacylglycerols, triacylglycerols) when compared with the ileal microsomal fraction. These data suggest that (1) jejunal and ileal microsomal membranes differ from each other in terms of lipid composition and lipid synthesis, (2) site variations in the specificity of acyltransferases for different fatty acids exist, and (3) higher delta 9-, delta 6-, delta 5-, and delta 4-desaturase activities exist in ileal compared with jejunal enterocytes.

Animals↗

Modulation of receptor-mediated gonadotropin action in rat testes by dietary fat.

The effect of feeding diets enriched with 18:2 omega 6, 18:3 omega 3, or saturated fatty acids on lipid composition and receptor-mediated action of luteinizing hormone/human chorionic gonadotropin (LH/hCG) in rat testicular plasma membranes was investigated. Linoleic and alpha-linolenic acid treatments reduced total phospholipid and cholesterol content of the testicular plasma membrane and altered membrane phospholipid composition. Change in phospholipid and cholesterol content after feeding the polyunsaturated fats decreased cholesterol to phospholipid ratios and binding capacity of the LH/hCG receptor in the testicular plasma membrane. LH-stimulated adenylate cyclase activity was decreased in animals fed the linolenic acid-rich diet. NaF-stimulated adenylate cyclase activity was decreased in animals fed diets high in either polyunsaturated fatty acid. Decreased plasma membrane LH/hCG receptor content was associated with decreased testosterone production in Leydig cells in response to LH in the linolenic acid-fed group. It is suggested that change in cholesterol-to-phospholipid ratios alters the physical properties of testicular plasma membranes in a manner that influences accessibility of LH/hCG receptors in testicular tissue.

Adenylyl Cyclases↗

Mortality-associated factors in infected lymphoma patients.

Three hundred eighty-eight medical records of patients with lymphoma seen between 1971 and 1980 were analyzed for factors related to infection-associated mortality. Infection occurred in 100 patients (36 Hodgkin's lymphoma [HL], and 64 non-Hodgkin's lymphoma [NHL]). The overall mortality with infection was 17% (6 of 36) for HL and 52% (33 of 64) for NHL. In patients with NHL mortality correlated with infection in the respiratory tract (P less than or equal to 0.0001), blood (P less than or equal to 0.003), and multiple sites (P less than or equal to 0.0004) and with the following factors: granulocytopenia (P less than or equal to 0.05), thrombocytopenia (P less than or equal to 0.035), and cytotoxic therapy (P less than or equal to 0.034). Patients with HL showed a positive correlation only with staphylococcal infections (P less than or equal to 0.001) and monocytopenia (P less than or equal to 0.01). The above data may be used to generate a risk factor profile of patients at greater risk of mortality associated with such infections. Advance knowledge of such a profile may assist in the clinical management of these high-risk patients.

Adult↗

A new methodology for ancillary services review.

This study used life table analysis techniques to evaluate the daily charges generated for diagnostic tests, procedures, and therapies for a sample of patients without regard to diagnosis and for patients with a primary diagnosis of congestive heart failure. The study indicated that about 50% of all ancillary services ordered are accumulated by the 5th day of stay and 75% by the 9th day. Length-of-stay review (LOS) undertaken after the 9th day, therefore, affects only 25% of tests and treatments. A method is proposed to generate data useful for reviewing the diagnostic tests, procedures, and therapies ordered during the early days of a patient's hospital stay. This approach has relevance for cost control under the new diagnosis-related groups reimbursement plan.

Actuarial Analysis↗