Evidence for critical-period programming of intestinal transport function: variations in the dietary ratio of polyunsaturated to saturated fatty acids alters ontogeny of the rat intestine

2-week isocaloric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal transport in rats. This study was undertaken to test the hypotheses that (1) the fatty acid composition of a nutritionally adequate diet in early life has lasting consequences for active and passive intestinal transport processes; and (2) early life feeding experiences with diets of varying fatty acid composition influence the intestines' ability to adaptively up- or down-regulate intestinal transport in later life. Female Sprague-Dawley rats were weaned onto S or P and were maintained on these diets for 2, 10 or 12 weeks. An in vitro uptake technique was used in which the bulk phase was vigorously stirred to reduce the effective resistance of the intestinal unstirred water layer. P decreased and S increased the uptake of glucose, and this effect was progressive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased ileal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the ileal uptake of glucose. The ileal uptake of galactose increased as the animals grew on either P or S. Switching from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switching from S to P. The effect of feeding P or S on hexose uptake was influenced by the animals' dietary history: ileal glucose and galactose uptake was lower in animals fed P at an early age (PSP) than in animals fed P for the first time in later life (SSP). Jejunal glucose and galactose uptake was also lower in animals fed S at an early age (SPS) than in those fed S for the first time in later life (PPS). The alterations in the uptake of long-chain saturated and unsaturated fatty acids and cholesterol did not progress with longer periods of feeding, and in the jejunum, lipid uptake did not change when switching from P to S or S to P. Early feeding with P (PSP vs. SSP) was associated with lower jejunal uptake of 18:3 and lower ileal uptake of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with lower ileal uptake of cholesterol. The changes in uptake of hexoses and lipids was not explained by differences in the animals' food consumption, body or intestinal weight or mucosal surface area.(ABSTRACT TRUNCATED AT 400 WORDS)     

Treatment of the enhanced intestinal uptake of glucose in diabetic rats with a polyunsaturated fatty acid diet

Intestinal absorption of most nutrients is enhanced in diabetic rats. We wished to test the hypothesis that manipulation of dietary fatty acids will modify enhanced uptake of glucose in rats with established streptozotocin-diabetes. Chow-fed control rats or animals with one week of streptozotocin-diabetes were continued on chow or were fed ad libitum for three weeks with semisynthetic isocaloric diets containing a high content of either essential polyunsaturated or non-essential saturated fatty acids. The jejunal and ileal in vitro uptake of varying concentrations of glucose was much higher in diabetic than control rats fed chow or the saturated fatty acid diet. In contrast, the enhanced uptake of this sugar was reduced or normalized in diabetic rats fed the polyunsaturated fatty acid diet. Feeding the polyunsaturated fatty acid diet was associated with increased brush-border membrane activity of alkaline phosphatase in diabetic jejunum and ileum, but neither the saturated fatty acid diet nor the polyunsaturated fatty acid diet altered brush-border membrane cholesterol or phospholipids in control or in diabetic rats. Mucosal surface area was similar in diabetic rats fed the saturated fatty acid diet or the polyunsaturated fatty acid diet. Thus, (1) feeding the polyunsaturated fatty acid diet diminishes the enhanced jejunal and ileal uptake of glucose in diabetic rats, and (2) the influence of the polyunsaturated fatty acid diet on uptake in diabetic rats was not explained by alterations in intestinal morphology or brush-border membrane content of cholesterol or phospholipids. This study suggests that manipulation of dietary lipids may play a role in the normalization of the enhanced intestinal glucose uptake in rats with established diabetes.     

Diet fat composition alters membrane phospholipid composition, insulin binding, and glucose metabolism in adipocytes from control and diabetic animals

The present study was designed to determine if diet fat-induced alteration in the fatty acid composition of the adipocyte plasma membrane alters insulin binding and the insulin responsiveness of glucose metabolism in control and diabetic states. Normal (control) and diabetic (streptozotocin-induced) rats were fed high fat semipurified diets providing a high or low polyunsaturated to saturated fatty acid (P/S) ratio. Feeding a high P/S diet increased the polyunsaturated fatty acid content of major membrane phospholipids of the adipocyte plasma membrane from both normal and diabetic animals. The diabetic state was associated with an elevated content of linoleic acid and a reduced level of arachidonic acid consistent with reduced delta 6-desaturation. Feeding the high P/S diet to diabetic animals increased membrane linoleic acid content and prevented the decrease observed in the arachidonic acid of membrane phospholipids. The high P/S diet was associated with increased insulin binding in nondiabetic animals but did not change the amount of insulin bound by cells from diabetic animals. Significantly (p less than 0.05) increased rates of insulin-stimulated glucose transport and lipogenesis (glucose incorporation into lipids) were observed in control animals fed the high as compared to the low P/S diet. The rates of insulin-stimulated glucose transport, oxidation, and lipogenesis were lower (p less than 0.05) for cells from diabetic as compared to control animals. However, feeding a high P/S diet significantly improved rates for all three of these functions (p less than 0.05). It is concluded that diet-induced alterations in membrane composition may provide a mechanism for improving the cellular response to insulin in cells from diabetic animals.     

Spectrum of effects of dietary long-chain fatty acids on rat intestinal glucose and lipid uptake

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0-12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.     

Effects of prolonged ingestion of glucose or ethanol on tissue lipid composition and lipid biosynthesis in rat

The effects on lipid metabolism of long-term feeding of large amounts of ethanol or glucose differed from those that have been reported in short-term experiments. Three groups of male rats were investigated. The first was fed lab chow and 15% (v/v) ethanol ad lib.; the second was pair-fed with the first and given isocaloric amounts of glucose in lieu of ethanol; the third was fed lab chow and water ad lib. All three groups consumed nearly the same number of calories, and about 30% of the calories in the first group were derived from ethanol. Neither glucose nor ethanol added to a nutritionally adequate diet promoted the development of a fatty liver, although both stimulated acetate-(14)C utilization for hepatic lipid synthesis. In all three groups more than 80% of the label in hepatic lipid was found in fatty acids, and the distribution of label amongst the fatty acids of different chain lengths was virtually the same. Ethanol decreased while glucose increased the quantity of lipid in fat depots, and each altered the fatty acid composition of the lipids in adipose tissue, kidney, liver, and hepatic subcellular fractions in a different manner. The most striking of these changes was the relative increase in monounsaturated fatty acids and the decrease in essential fatty acids produced by glucose.     

Influence of dietary linseed oil and sunflower seed oil on some mechanical and metabolic parameters of isolated working rat hearts

The role played by membrane lipid environment on cardiac function remains poorly defined. The polyunsaturated fatty acid profile of myocardial phospholipids could be of utmost importance in the regulation of key-enzyme activities. This study was undertaken to determine whether selective incorporation of n-6 or n-3 fatty acids in membrane phospholipids might influence cardiac mechanical performances and metabolism. For 8 wk, male weaning Wistar rats were fed a semi-purified diet containing either 10% sunflower seed oil (72% C18:2 n-6) or 10% linseed oil (54% C18:3 n-3) as the sole source of lipids. The hearts were then removed and perfused according to working mode with a Krebs-Henseleit buffer containing glucose (11 mM) and insulin (10 Ul/l). Cardiac rate, coronary and aortic flows and ejection fraction were monitored after 30 min of perfusion. Myocardial metabolism was estimated by evaluating the intracellular fate of 1-14C palmitate. Sunflower seed oil and linseed oil feeding did not modify either coronary or aortic flow, which suggests that cardiac mechanical work was not affected by the diets. Conversely, cardiac rate was significantly decreased (-18%; P less than 0.01) when rats were fed the n-3 polyunsaturated fatty acid rich diet. Radioanalysis of the myocardial metabolism suggested that replacing n-6 polyunsaturated fatty acids by n-3 polyunsaturated fatty acids: i) did not alter palmitate uptake; ii) prolonged palmitate incorporation into cardiac triglycerides; iii) reduced beta-oxidation of palmitic acid. These results support the assumption that dietary fatty acids, particularly n-6 and n-3 fatty acids, play an important role in the regulation of cardiac mechanical and metabolic activity.     

Dietary effects of omega 3-fatty acids on intestinal transport function

Animals were fed for 2 weeks on one of four isocaloric and isocholesterolic semisynthetic diets: high 18:3 omega 3, low 18:3 omega 3, high 20:5 omega 3, or low 20:5 omega 3. The weight of the intestine and the percentage of the wall consisting of mucosa was greater in high 20:5 omega 3 than in high 18:3 omega 3, and greater in low 20:5 omega 3 than in low 18:3 omega 3, although the mucosal surface area was 26% lower in high 20:5 omega 3 than high 18:3 omega 3. The jejunal uptake of 40 mM glucose and ileal uptake of 40 mM galactose was greater in high 18:3 omega 3 than in high 20:5 omega 3, jejunal uptake of fatty acid 12:0 was higher, but 18:0 was lower in high 18:3 omega 3 than in high 20:5 omega 3. The jejunal or ileal uptake of cholesterol was not affected by 20:5 omega 3. However, 20:5 omega 3 had a variable effect on the uptake of medium- and long-chain fatty acids. Alterations in the uptake of fatty acids and glucose were not explained by any difference in the animals' food consumption, body weight gain, or intestinal weight, but the reduced jejunal uptake of 40 mM glucose in rats fed the high 20:5 omega 3 diet was associated with reduced mucosal surface area. Thus, (i) varying the source of omega 3-fatty acids (vegetable, 18:3 omega 3 versus fish oil, 20:5 omega 3) altered the mucosal mass of the intestine, and (ii) the source of the dietary omega 3-fatty acid (18:3 omega 3 versus 20:5 omega 3) influenced intestinal hexose uptake, with fish oil having an anti-absorptive effect on the jejunal uptake of D-glucose.     

Dietary lipids modify the age-associated changes in intestinal uptake of fructose in rats

Because reduced nutrient absorption may contribute to malnourishment in the elderly, age and diet modulate fructose uptake in mice, and alterations in fructose uptake may be paralleled by changes in the abundance of fructose transporters, the objectives of this study were to determine 1) the effects of aging on fructose absorption in rats, 2) the effect of feeding diets enriched with saturated fatty acids (SFA) vs. polyunsaturated fatty acids (PUFA), and 3) the mechanisms of these age-and diet-associated changes. Male Fischer 344 rats aged 1, 9, and 24 mo received isocaloric diets enriched with SFA or PUFA. The uptake of (14)C-labeled D-fructose was determined in vitro using the intestinal sheet method. Northern and Western blot analyses and immunohistochemistry were used to determine the abundance of sodium-independent glucose and fructose transporters (GLUT)2 and GLUT5. When expressed on the basis of mucosal surface area, jejunal fructose uptake was increased in 9 and 24 mo compared with 1-mo-old animals fed SFA. PUFA-fed animals demonstrated increased fructose uptake at 24 mo compared with younger animals. Ileal fructose uptake was increased with SFA vs. PUFA in 9-mo-old rats but was reduced with SFA in 1- and 24-mo-old rats. Variations in GLUT2 and GLUT5 abundance did not parallel changes in uptake. These results indicate that 1) age increases fructose uptake when expressed on the basis of mucosal surface area, 2) age influences the adaptive response to dietary lipid modifications, and 3) alterations in fructose uptake are not explained by variations in GLUT2 or GLUT5.     

Diets alter jejunal morphology and brush border membrane composition in streptozotocin-diabetic rats

Previous studies have demonstrated enhanced active and passive uptake of many nutrients in animals with experimental diabetes. These changes in absorption cannot be explained by differences in intestinal morphology, although the brush border membrane (BBM) phospholipids do change in diabetes. Manipulation of diet produces alterations in intestinal uptake of lipids and glucose. This study was undertaken to determine the effect of diet and diabetes on jejunal morphology and BBM lipid composition. Rats were rendered hyperglycemic with streptozotocin and were fed for 2 weeks on a diet that was high or low in carbohydrate, essential fatty acids, cholesterol, or protein. In both control and diabetic rats, these diets produced changes in villus height and BBM sucrase and alkaline phosphatase activities. In both control and diabetic rats, BBM phospholipids were unaffected by changes in the dietary content of essential fatty acids, cholesterol, or protein, but total BBM phospholipid content was reduced in animals fed low as compared with high carbohydrate diet. Total BBM phospholipid content was higher in diabetic than in control animals fed the low protein diet, whereas BBM phospholipid content was lower in diabetic than in control animals fed the high carbohydrate diet, and was even lower in diabetic animals fed the low as compared with the high carbohydrate diet. These changes in total phospholipids were due to alterations in the BBM content of phospholipids containing choline. In control animals, BBM cholesterol was higher in rats fed the low as compared with the high cholesterol diet, or the low as compared with the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites.

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.     

Fatty liver produced by dietary deficiencies: its pathogenesis and potentiation by ethanol

In a study of the pathogenesis of hepatic fat accumulation under experimental conditions mimicking chronic alcoholism, rats were fed a low-fat diet, deficient in amino acids and choline, containing either ethanol or isocaloric amounts of carbohydrate. Dietary deficiencies alone produced a moderately fatty liver after 24 days. The combination of ethanol and dietary deficiencies resulted in enhanced lipid accumulation, which was apparent after only 11 days. In an investigation of the origin of hepatic triglyceride fatty acids, the experiment was repeated after the adipose lipids had been marked by the feeding of oils containing characteristic fatty acids (linseed oil, containing linolenate, or coconut oil, containing laurate and myristate). In all animals, the fatty acid composition of the hepatic triglycerides differed markedly from that of adipose tissue; it had a larger percentage of endogenously synthesized fatty acids and a five times smaller percentage of the marker fatty acids. In addition, ethanol feeding resulted in a greater retention of the marker fatty acids in the adipose tissue. Thus, the deposition of hepatic triglycerides produced by the feeding of deficient diets is markedly potentiated by ethanol; the triglyceride fatty acids accumulated under these conditions appear to originate, for the most part, not from mobilization of depot fat, but from endogenous synthesis.     

Isoproterenol-induced mortality and cardiac lipids of aspirin-pretreated rats with various fat intakes

The effect of altering cardiac concentrations of precursors and inhibitors of prostaglandin synthesis by varying fat intake was determined in rats injected with the cardiotoxic drug isoproterenol, following pretreatment with aspirin or potassium phosphate buffer solution. Prior to injection, four groups of rats were fed either a low-fat diet (3.7 energy percent coconut oil 3.7 energy percent safflower oil) or a high-fat diet (3.7 energy percent safflower oil-36.4 energy percent coconut oil mixture or 40.1 energy percent safflower oil.) Mortality as well as fatty acid composition of cardiac lipids changed in response to altered kinds and amounts of fats. Mortality and cardiac C20:4/C22:6 ratio were lowered by feeding 3.7 energy percent coconut oil, and increased by feeding 40.1 energy percent safflower oil. Aspirin reduced mortality in rats fed 40.1 energy percent safflower oil, but not in rats fed other diets. Results suggest that dietary manipulations which increase tissue content of polyunsaturated fatty acids of the n-6 type relative to those of the n-3 type may increase sensitivity to isoproterenol, and that effectiveness of aspirin in reducing isoproterenol-induced mortality depends upon the n-6/n-3 ratio of cardiac fatty acids.     

Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.     

Effect of dietary fats on linoleic acid metabolism. A radiolabel study in rats

Effects on the linoleic acid metabolism in vivo of three dietary fats, rich in either oleic acid, trans fatty acids or alpha-linolenic acid, and all with the same linoleic acid content, were investigated in male Wistar rats. After 6 weeks of feeding, the rats were intubated with [1-14C]linoleic acid and [3H]oleic acid. The incorporation of these radiolabels into liver, heart and serum was investigated 2, 4, 8, 24 and 48 h after intubation. The amount of 14C-labelled arachidonic acid incorporated into the liver phospholipid of the group fed the oleic acid-rich diet was significantly higher than that of the other groups. However, compared to the trans fatty acids-containing diet, the oleic acid-rich diet induced only a slightly higher arachidonic acid level in the phospholipid fraction of the tissues as determined by GLC. Dietary alpha-linolenic acid more than halved the arachidonic acid levels. Our results do not support the hypothesis that the delta 6-desaturase system actually determines the polyunsaturated fatty acid levels in tissue lipids by regulating the amount of polyunsaturated fatty acids (e.g., arachidonic acid) synthesized. The biosynthesis of polyunsaturated fatty acids only is not sufficient to explain the complicated changes in fatty acid compositions as observed after feeding different dietary fats.     

The Beneficial Effects of n-3 Polyunsaturated Fatty Acids on Diet Induced Obesity and Impaired Glucose Control Do Not Require Gpr120

GPR120 (Ffar4) has been postulated to represent an important receptor mediating the improved metabolic profile seen upon ingestion of a diet enriched in polyunsaturated fatty acids (PUFAs). GPR120 is highly expressed in the digestive system, adipose tissue, lung and macrophages and also present in the endocrine pancreas. A new Gpr120 deficient mouse model on pure C57bl/6N background was developed to investigate the importance of the receptor for long-term feeding with a diet enriched with fish oil. Male Gpr120 deficient mice were fed two different high fat diets (HFDs) for 18 weeks. The diets contained lipids that were mainly saturated (SAT) or mainly n-3 polyunsaturated fatty acids (PUFA). Body composition, as well as glucose, lipid and energy metabolism, was studied. As expected, wild type mice fed the PUFA HFD gained less body weight and had lower body fat mass, hepatic lipid levels, plasma cholesterol and insulin levels and better glucose tolerance as compared to those fed the SAT HFD. Gpr120 deficient mice showed a similar improvement on the PUFA HFD as was observed for wild type mice. If anything, the Gpr120 deficient mice responded better to the PUFA HFD as compared to wild type mice with respect to liver fat content, plasma glucose levels and islet morphology. Gpr120 deficient animals were found to have similar energy, glucose and lipid metabolism when fed HFD PUFA compared to wild type mice. Therefore, GPR120 appears to be dispensable for the improved metabolic profile associated with intake of a diet enriched in n-3 PUFA fatty acids.     

Insulin binding to liver nuclei from lean and obese mice is altered by dietary fat.

Insulin binding to the plasma membrane is known to be altered by modifying the membrane composition through dietary treatment. As insulin binding receptors are also present on nuclear membrane, this study was undertaken to investigate if specific binding of insulin to the liver nuclei is altered by diet. 8-wk-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low polyunsaturated-to-saturated (P/S) fatty acid ratio for 4 wk. Liver nuclei were prepared, insulin binding was measured and nuclear phospholipids were isolated for lipid analysis. Insulin binding was highest in nuclei prepared from lean mice fed a high P/S diet. Specific binding of insulin to nuclei prepared from obese mice was also increased by the high P/S diet, but to a lesser extent compared to lean mice. Feeding a high P/S diet increased polyunsaturated fatty acid content of membrane phospholipids from both lean and ob/ob mice. Obese mice were characterized by higher levels of arachidonic acid and lower levels of linoleic acid in phosphatidylcholine. The present study establishes that insulin binding to liver nuclei is increased by feeding a high P/S diet, and that insulin binding to liver nuclei from obese mice is lower than from lean mice.     

Chronic ethanol feeding inhibits plasma levels of insulin-like growth factor-1

The purpose of this study was to determine whether the generalized catabolic effects of chronic ethanol may be associated with a decline in plasma levels of insulin-like growth factor-1 (IGF-1). Male Sprague-Dawley rats were fed a liquid diet containing 5% ethanol or pair-fed a diet made isocaloric with maltose-dextrin. Animals were maintained on this diet for either 12 days or 4.5 months. Another group of animals were fed control diet ad libitum for 2 weeks. After 12 days of feeding, plasma concentrations of IGF-1 in ad libitum fed rats were 771 +/- 41 ng/ml which was greater than concentrations in either pair-fed (595 +/- 23 ng/ml) or ethanol-fed (680 +/- 40 ng/ml) rats (P less than 0.05). After 4.5 months of feeding, plasma levels of IGF-1 in ad libitum and pair-fed rats were similar to the 12 day study (736 +/- 56 and 607 +/- 26 ng/ml, respectively). However, a significant decrease in plasma levels of IGF-1 was observed in ethanol-fed animals over the 4.5 month period (551 +/- 28 ng/ml, P less than 0.05). Results of a similar study in rats fed a high-fat diet for 4.5 months were similar to those found with the low-fat diet. These results indicate that 1) dietary restriction of the type routinely used in this pair-feeding regimen decreases plasma levels of IGF-1, 2) chronic ethanol feeding further decreases plasma IGF-1 levels compared to pair-fed rats, 3) the effects of ethanol on IGF-1 concentrations are not modified by dietary fat, and 4) the effects on IGF-1 are not directly dependent on elevated plasma ethanol concentrations. Our results suggest that IGF-1 secreting cells in the liver may be progressively damaged by chronic ethanol feeding.