Effects of Timing of Medium-Chain Triglycerides (8:0 and 10:0) Supplementation during the Day on Muscle Mass, Function and Cognition in Frail Elderly Adults.

OBJECTIVES: Supplementation with 6 g/day of medium-chain triglycerides (MCTs) at dinnertime increases muscle function and cognition in frail elderly adults relative to supplementation with long-chain triglycerides. However, suitable timing of MCT supplementation during the day is unknown. DESIGN: We enrolled 40 elderly nursing home residents (85.9 ± 7.7 years) in a 1.5-month randomized intervention trial. Participants were randomly allocated to two groups: one received 6 g/day of MCTs at breakfast (breakfast group) as a test group and the other at dinnertime (dinner group) as a positive control group. MEASUREMENTS: Muscle mass, strength, function, and cognition were monitored at baseline and 1.5 months after initiation of intervention. RESULTS: Thirty-seven participants completed the study and were included in the analysis. MCT supplementation in breakfast and dinner groups respectively increased right arm muscle area from baseline by 1.1 ± 0.8 cm2 (P<0.001) and 1.6 ± 2.5 cm2 (P<0.001), left arm muscle area by 1.1 ± 0.7 cm2 (P<0.001) and 0.9 ± 1.0 cm2 (P<0.01), right knee extension time by 39 ± 42 s (P<0.01) and 20 ± 32 s (P<0.05), leg open and close test time by 1.74 ± 2.00 n/10 s (P<0.01) and 1.67 ± 2.01 n/10 s (P<0.01), and Mini-Mental State Examination score by 1.5 ± 3.0 points (P=0.06) and 1.0 ± 2.1 points (P=0.06). These increases between two groups did not differ statistically significantly. CONCLUSION: Supplementation with 6 g MCTs/day for 1.5 months, irrespective of ingestion at breakfast or dinnertime, could increase muscle mass and function, and cognition in frail elderly adults.

The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes.

PPARgamma is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARgamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARgamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.

Different effects of two proteinase inhibitors on insulin-induced cellular responses in rat adipocytes.

Among various proteinase inhibitors, N-acetyl-L-tyrosine ethyl ester (ATEE), a chymotrypsin substrate analog, and N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), a trypsin inhibitor, showed significant inhibitory effects on insulin stimulated glucose transport in rat adipocytes. ATEE did not affect insulin binding, but inhibited insulin internalization. In intact adipocytes, ATEE inhibited tyrosine phosphorylation of the beta-subunit of the insulin receptor, a 170 kDa protein and a 60 kDa protein at almost the same concentration (ID50 = 0.24 +/- 0.05 mM, n = 4, mean +/- S.E.), but in a plasma membrane fraction, ATEE did not appreciably inhibit the tyrosine phosphorylation of the beta-subunit of the insulin receptor, TLCK did not inhibit insulin binding. At 0.25 mM, TLCK did not inhibit insulin internalization, but inhibited 70% of the insulin-stimulated glucose transport (ID50 = 0.19 +/- 0.02 mM, n = 7). TLCK inhibited insulin internalization at more than 0.25 mM. TLCK did not inhibit the tyrosine phosphorylation of the beta-subunit of the insulin receptor in intact cells or in the plasma membrane fraction. In intact cells, TLCK inhibited the phosphorylation of the 60 kDa protein and simultaneously it stimulated the phosphorylation of the 170 kDa protein more than 3-fold. These results indicate that there are at least two sites in the insulin-induced signal transduction pathway where proteinase inhibitors act to suppress the insulin signal transduction. A major ATEE site is very close to phosphorylation of the beta-subunit of the insulin receptor. On the other hand, TLCK inhibits a step(s) in the signal transduction pathway after the insulin receptor but before the glucose transporter.

Role of two types of glucose transporters in enlarged adipocytes from aged obese rats.

The mechanism of insulin-resistant glucose-transport activity in enlarged aged adipocytes was examined. Glucose-transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of HepG2 erythrocyte/glucose transporter (GLUT1), and the muscle/adipose tissue transporter (GLUT4) was estimated by immunoblotting. Basal glucose-transport activity increased 6.3-fold/cell but remained constant per unit cellular surface area due to cell enlargement. Maximal insulin-stimulated transport activity remained constant per cell but decreased per unit cellular surface area. On a per protein basis, GLUT1 and GLUT4 from aged rats decreased to approximately 60 and 10% of those from young rats, respectively. However, when the protein content of each fraction and the recoveries of marker enzymes were used for estimating the amount of transporters in intact adipocytes, the amount of GLUT1 per cell remained relatively constant, whereas that of GLUT4 decreased. In basal cells from young rats, 31% of the total GLUT1 per cell was located in the plasma membrane, whereas in those from aged rats, 63% was located in the plasma membrane. Thus, in comparing basal adipocytes from aged rats with those from young rats, GLUT1 per cell in the plasma membrane increased 2.8-fold, but this increase was less than that of transport activity (6.3-fold). In basal cells from young rats, 8% of the total GLUT4 was located in the plasma membrane, and a 4.5-fold increase was observed with insulin treatment, but the amount of GLUT4 in each fraction from aged rats markedly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training increases glucose transporter content in skeletal muscles more efficiently from aged obese rats than young lean rats.

Glucose uptake in rat skeletal muscles decreases with age and obesity, but increases with chronic exercise training. The purpose of our study was to determine whether the GLUT4 content in several skeletal muscles from 1-mo-old young, lean rats and 12-mo-old aged, obese rats alters with exercise training. For exercise, a treadmill run of approximately 1 km/day was made for 4 wk by both groups of rats. The concentration of GLUT4 per protein in membrane fraction from several skeletal muscles was measured by immunoblotting. The amount of GLUT4 in the gastrocnemius and white quadriceps from aged rats slightly but significantly decreased to 73% and 78% of that from young rats, respectively. However, no significant difference in GLUT4 amount in the soleus, plantaris, and red quadriceps was observed between young and aged rats. The exercise training resulted in a larger increase in the amount of GLUT4 in each muscle from aged rats than in muscles from young rats. In aged rats, GLUT4 amount increased significantly with exercise training by 30, 33, 41, and 27% in the soleus, plantaris, gastrocnemius, and red quadriceps, respectively, compared with the sedentary controls. However, in young rats, exercise-induced increase of GLUT4 amount was significant only in the plantaris, and the increase was 17%. In exercised aged, obese rats, decreases of body weight, plasma triglyceride levels, and plasma free fatty acid were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-alpha and uncoupling protein (UCP)-2 mRNA levels increased 12- and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-alpha induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-alpha mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.

Mitochondrial uncoupling protein 3 (UCP3) in skeletal muscle.

Mitochondrial uncoupling protein (UCP), mitochondrial transporters, function as a proton channel and increase thermogenesis. UCP1 is expressed in brown adipose tissues (BAT), UCP2 is widely expressed in multiple tissues, while UCP3 is expressed in skeletal muscle. Thus, UCPs, especially UCP3, in skeletal muscles is a good candidates for prevention of obesity and diabetes. However, the role of UCP3 in skeletal muscle for energy expenditure and obesity has been controversial. There is some evidence that the UCP3 is possibly regulated by energy substrate, such as lipid and glucose. These observations suggest that increased energy substrate entry in muscle results in an increase in UCP3 expression which leads to an increase in energy expenditure.

Localization of Na(+)-dependent active type and erythrocyte/HepG2-type glucose transporters in rat kidney: immunofluorescence and immunogold study.

Glucose is actively taken up from the glomerular filtrate into the tubule cells by the Na(+)-dependent active glucose transporter (GT), and passively crosses the basolateral membrane via facilitated diffusion GT. With the use of antibodies directed against two types of GTs, we show the immunocytochemical localization of the Na(+)-dependent active GT (SGLT1) and the erythrocyte/HepG2-type facilitated diffusion GT (GLUT1). For light microscopic observation, frozen sections were stained by the rhodamine labeling method. Counterstaining with fluorescein-phalloidin and 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) was employed to facilitate cell type identification. Immunogold staining was carried out on ultra-thin frozen sections for electron microscopy. The antibody to SGLT1 reacted with a 77 KD protein in immunoblotting of a kidney lysate. By immunocytochemistry, SGLT1 was localized in the microvillous plasma membrane in the apical brush borders of the cells of all three proximal tubule segments (S1, S2, and S3). The antibodies to GLUT1, a member of the facilitated diffusion GT family, were raised against human erythrocyte GT or synthetic oligopeptides derived from HepG2 GT, which reacted with a 48 KD protein in immunoblotting of the kidney lysate. GLUT1 was found at the basolateral plasma membranes of S3 proximal tubule cells, cells of the thick limb of Henle's loop, and collecting duct cells. Combined with known physiological data, our findings suggest that SGLT1 in the apical plasma membrane of the proximal tubule cells is responsible for the Na(+)-dependent active reabsorption of glucose from the glomerular filtrate. GLUT1 in the basolateral plasma membrane of S3 cells may transport reabsorbed glucose to the blood vessels. GLUT1 in the basolateral plasma membranes of cells of the thick limb of Henle's loop and of the collecting duct, on the other hand, may nourish these metabolically active cells by facilitating the diffusion of extracellular glucose provided from blood through the basolateral side of the cells.

Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in the ciliary body and iris of the rat eye.

Aqueous humor, with its unique low concentration of proteins, is produced by the ciliary body and isolated by the blood-aqueous barrier from the body fluid. Glucose in aqueous humor is a major source of nutrients for lens and corneal cells, and is maintained near the plasma level, suggesting a specific glucose transport mechanism in the blood-aqueous barrier. Using antibodies against erythrocyte/HepG2-type glucose transporter (GLUT1), one isoform of the facilitated diffusion glucose transporters, the authors found immunocytochemically that GLUT1 localizes in the epithelial cells of ciliary body and iris. GLUT1 is also found in the endothelial cells of blood vessels in the iris, whereas no labeling is seen in the blood vessels in the ciliary body. In the ciliary body epithelium, the plasma membranes of both the pigmented epithelial (PE) and nonpigmented epithelial (NPE) cells are positive for GLUT1. By the colloidal gold particle counting, the basal infoldings of PE cells show approximately two-fold denser labeling than those of NPE cells. Since PE and NPE cells make up a functional syncytium with numerous gap junctions, the authors suggest that glucose transport in the ciliary body occurs in this manner: glucose diffuses out from blood vessels through the pores of fenestrated endothelial cells, is transported into PE cells by GLUT1 in their plasma membrane, enters NPE cells through gap junctions connecting PE and NPE cells, and is finally transported into the aqueous humor by GLUT1 of NPE cells. The higher density of GLUT1 in PE cells may account for the consumption of glucose by PE and NPE cells in addition to the transepithelial transport.

Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat.

The blood-retinal barrier is part of the blood-ocular barrier. Retinal pigment epithelial cells connected by tight junctions serve as an outer blood-retinal barrier, and the nonfenestrated endothelial cells of blood vessels sealed by tight junctions serve as an inner blood-retinal barrier. Using antibodies specific for the erythrocyte/HepG2-type glucose transporter (GLUT1), one isoform of facilitated-diffusion glucose transporters, it was found, by ultrastructural cytochemical examination, that GLUT1 in the rat was localized at both the apical and basolateral plasma membranes of retinal pigment epithelial cells. The fenestrated endothelial cells of the underlying choriocapillaries were negative for GLUT1. In the inner retina, GLUT1 was found at both the luminal and contraluminal plasma membranes of endothelial cells. These observations show that GLUT1 is concentrated at the critical plasma membranes of the blood-retinal barrier and may serve as the machinery for glucose transport across the barrier.

High-fat diet-induced hyperglycemia and obesity in mice: differential effects of dietary oils.

Mice fed a high-fat diet develop hyperglycemia and obesity. Using non-insulin-dependent diabetes mellitus (NIDDM) model mice, we investigated the effects of seven different dietary oils on glucose metabolism: palm oil, which contains mainly 45% palmitic acid (16:0) and 40% oleic acid (18:1); lard oil, 24% palmitic and 44% oleic acid; rapeseed oil, 59% oleic and 20% linoleic acid (18:2); soybean oil, 24% oleic and 54% linoleic acid; safflower oil, 76% linoleic acid; perilla oil, 58% alpha-linolenic acid; and tuna fish oil, 7% eicosapentaenoic acid and 23% docosahexaenoic acid. C57BL/6J mice received each as a high-fat diet (60% of total calories) for 19 weeks (n = 6 to 11 per group). After 19 weeks of feeding, body weight induced by the diets was in the following order: soybean > palm > or = lard > or = rapeseed > or = safflower > or = perilla > fish oil. Glucose levels 30 minutes after a glucose load were highest for safflower oil (approximately 21.5 mmol/L), modest for rapeseed oil, soybean oil, and lard (approximately 17.6 mmol/L), mild for perilla, fish, and palm oil (approximately 13.8 mmol/L), and minimal for high-carbohydrate meals (approximately 10.4 mmol/L). Only palm oil-fed mice showed fasting hyperinsulinemia (P < .001). By stepwise multiple regression analysis, body weight (or white adipose tissue [WAT] weight) and intake of linoleic acid (or n-3/n-6 ratio) were chosen as independent variables to affect glucose tolerance. By univariate analysis, the linoleic acid intake had a positive correlation with blood glucose level (r = .83, P = .02) but not with obesity (r = .46, P = .30). These data indicate that (1) fasting blood insulin levels vary among fat subtypes, and a higher fasting blood insulin level in palm oil-fed mice may explain their better glycemic control irrespective of their marked obesity; (2) a favorable glucose response induced by fish oil feeding may be mediated by a decrease of body weight; and (3) obesity and a higher intake of linoleic acid are independent risk factors for dysregulation of glucose tolerance.

High-monounsaturated fat diet-induced obesity and diabetes in C57BL/6J mice.

A high-monounsaturated fat diet has been proposed as a palatable alternative to a high-carbohydrate diet in diabetic patients, but it is unknown whether a higher intake of monounsaturated fat induces obesity and diabetes, as usually observed with other types of fat. To answer this question, C57BL/6J mice were divided into three groups: the first group was given a high-carbohydrate diet, and the other two groups were given a high-monounsaturated fat diet (60% of total energy) as olive oil or synthetic triolein for 4 months. It has been previously reported that the C57BL/6J mouse has a genetic predisposition for intraabdominal obesity and non-insulin-dependent diabetes mellitus (NIDDM) by high-polyunsaturated fat (n-6) feeding. Although there were no significant differences in energy intake and fat absorption among these three groups, compared with the high-carbohydrate diet, both high-monounsaturated fat diets produced hyperglycemia, obesity, and triglyceride accumulation in the liver and skeletal muscle. These data indicate that the recently recommended high-monounsaturated fat diet might induce obesity and diabetes.

Radioimmunoassay for human insulin-like growth factor-I receptor: applicability to breast carcinoma specimens and cell lines.

A radioimmunoassay for the human insulin-like growth factor-I (IGF-I) receptor was developed using a rabbit polyclonal antibody to the human IGF-I receptor and a highly purified IGF-I receptor. The purified receptor was radiolabeled with 125I-Bolton-Hunter reagent. Over 18% of the radiolabeled receptor was immunoprecipitated with the polyclonal antireceptor antibody. Purified IGF-I receptor concentrations as low as 5 ng/0.5 mL inhibited the radiolabeled IGF-I receptor binding. Purified insulin receptor weakly inhibited this binding, while the ligand IGF-I did not show inhibition. The radioimmunoassay was applicable to the measurements of IGF-I receptors in the Triton X-100 extracts of various tissues and cells. Breast cancer tissues and cells showed detectable IGF-I receptors, which correlated with IGF-I ligand binding. Receptor content was measurable in placenta and IM-9 cells, but receptor content was not measurable in liver and muscle extracts.

Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle.

This study was performed to assess the effects of short-term, extremely high-intensity intermittent exercise training on the GLUT-4 content of rat skeletal muscle. Three- to four-week-old male Sprague-Dawley rats with an initial body weight ranging from 45 to 55 g were used for this study. These rats were randomly assigned to an 8-day period of high-intensity intermittent exercise training (HIT), relatively high-intensity intermittent prolonged exercise training (RHT), or low-intensity prolonged exercise training (LIT). Age-matched sedentary rats were used as a control. In the HIT group, the rats repeated fourteen 20-s swimming bouts with a weight equivalent to 14, 15, and 16% of body weight for the first 2, the next 4, and the last 2 days, respectively. Between exercise bouts, a 10-s pause was allowed. RHT consisted of five 17-min swimming bouts with a 3-min rest between bouts. During the first bout, the rat swam without weight, whereas during the following four bouts, the rat was attached to a weight equivalent to 4 and 5% of its body weight for the first 5 days and the following 3 days, respectively. Rats in the LIT group swam 6 h/day for 8 days in two 3-h bouts separated by 45 min of rest. In the first experiment, the HIT, LIT, and control rats were compared. GLUT-4 content in the epitrochlearis muscle in the HIT and LIT groups after training was significantly higher than that in the control rats by 83 and 91%, respectively. Furthermore, glucose transport activity, stimulated maximally by both insulin (2 mU/ml) (HIT: 48%, LIT: 75%) and contractions (25 10-s tetani) (HIT: 55%, LIT: 69%), was higher in the training groups than in the control rats. However, no significant differences in GLUT-4 content or in maximal glucose transport activity in response to both insulin and contractions were observed between the two training groups. The second experiment demonstrated that GLUT-4 content after HIT did not differ from that after RHT (66% higher in trained rats than in control). In conclusion, the present investigation demonstrated that 8 days of HIT lasting only 280 s elevated both GLUT-4 content and maximal glucose transport activity in rat skeletal muscle to a level similar to that attained after LIT, which has been considered a tool to increase GLUT-4 content maximally.

Effect of dietary Platycodon grandiflorum on the improvement of insulin resistance in obese Zucker rats.

The effect of dietary Platycodon grandiflorum on the improvement of insulin resistance and lipid profile was investigated in lean (Fa/-) and obese (fa/fa) Zucker rats, a model for noninsulin dependent diabetes mellitus. Dietary Platycodon grandiflorum feeding for 4 weeks resulted in a significant decrease in the concentration of plasma triglyceride in both lean and obese Zucker rats. Furthermore, dietary Platycodon grandiflorum markedly decreased both plasma cholesterol and fasting plasma insulin levels, and significantly decreased the postprandial glucose level at 30 min during oral glucose tolerance test in obese Zucker rats. Although there was no statistical significance, the crude glucose transporter 4 protein level of obese rats fed Platycodon grandiflorum tended to increase when compared with that of obese control rats. Therefore, the present results suggested that dietary Platycodon grandiflorum may be useful in prevention and improvement of metabolic disorders characterized by hyperinsulinemia states such as noninsulin dependent diabetes mellitus, syndrome X, and coronary artery disease.

Effect of the fat/carbohydrate ratio in the diet on obesity and oral glucose tolerance in C57BL/6J mice.

To study whether consumed dietary fat has a linear relationship or a threshold with glycemic controls, female C57BL/6J mice were fed different levels of a safflower oil (10, 20, 30, 40, 50, and 60% of total energy) diet ad libitum for 15 wk. Food intake, body weight, parametrial white adipose tissue (WAT) and liver weight were measured, and oral glucose tolerance tests were conducted. Although there was no significant difference in average energy intake, graded increments of safflower oil resulted in graded deterioration of glucose tolerance during 5 and 12-wk feeding, and deterioration of glucose tolerance was more manifested after 12-wk feeding as compared to 5-wk feeding. After 12-wk feeding, a significant deterioration of glucose tolerance was observed in diets of more than 40% fat. Graded increments of body weight and WAT weight were observed, and their weight increases were manifested in diets of more than 30% fat. These data indicated that the amount of dietary fat had an almost linear relationship with glucose tolerance, and significant differences were observed in mice fed diets more of than 40% fat.

Effects of Platycodon grandiflorum feeding on serum and liver lipid concentrations in rats with diet-induced hyperlipidemia.

To study the effect of Platycodon grandiflorum (P.g.) feeding on serum and liver lipid concentrations, diet-induced hyperlipidemic rats were fed diets containing 5% and 10% P.g. powder for 3 weeks. The P.g. feeding markedly decreased both serum and liver lipid concentrations in hyperlipidemic rats. Especially, 5% P.g. diet significantly decreased the concentrations of total cholesterol and triglycerides in serum and liver as compared with those of the hyperlipidemic control group. Dietary P.g. also induced a reduction in low-density lipoprotein (LDL)-cholesterol as well as an increase in the concentration of high-density lipoprotein (HDL)-cholesterol in serum. Furthermore, the atherogenic index was also low in rats fed P.g. diet. These results indicated that dietary P.g. may have a beneficial effect on preventing hypercholesterolemia and hyperlipidemia.

Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects.

Although important roles of dietary n-3 fatty acids in the prevention of coronary heart disease (CHD) have been suggested, long-term effects of dietary alpha-linolenic acid (ALA, 18:3n-3) have not yet been established under controlled conditions. We tested whether a moderate increase of dietary ALA affects fatty acids composition in serum and the risk factors of CHD. Oxidized LDL (OxLDL) was directly measured by ELISA using antibody specific to OxLDL. By merely replacing soybean cooking oil (SO) with perilla oil (PO) (i.e., increasing 3 g/d of ALA), the n-6/n-3 ratio in the diet was changed from 4:1 to 1:1. Twenty Japanese elderly subjects were initially given a SO diet for at least 6 mo (baseline period), a PO diet for 10 mo (intervention period), and then returned to the previous SO diet (washout period). ALA in the total serum lipid increased from 0.8 to 1.6% after 3 mo on the PO diet, but EPA and DHA increased in a later time, at 10 mo after the PO diet, from 2.5 to 3.6% and 5.3 to 6.4%, respectively (p<0.05), and then returned to baseline in the washout period. In spite of increases of serum n-3 fatty acids, the OxLDL concentration did not change significantly when given the PO diet. Body weight, total serum cholesterol, triacylglycerol, glucose, insulin and HbA1c concentrations, platelet count and aggregation function, prothrombin time, partial thromboplastin time, fibrinogen and PAI-1 concentration, and other routine blood analysis did not change significantly when given the PO diet. These data indicate that, even in elderly subjects, a 3 g/d increase of dietary ALA could increase serum EPA and DHA in 10 mo without any major adverse effects.