Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor.

BACKGROUND: Growth hormone-releasing hormone (GHRH) has a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism. OBJECTIVES: To determine whether GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analyze the effects of GHRH on human adipocyte differentiation and lipolysis. METHODS: GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects. Human mesenchymal stem cells (HMSC) were differentiated to adipocytes with GHRH (10-14-10-8 M). Adipocyte differentiation, lipolysis and gene expression were measured and the effect of GH-R silencing was determined. RESULTS: Mature adipocytes from morbidly obese subjects showed a higher expression of GHRH and GH-R, and a lower expression of GHRH-R and GH than non-obese subjects (P<0.05). A total of 10-14-10-10 M GHRH induced an inhibition of lipid accumulation and PPAR-γ expression (P<0.05), and an increase in glycerol release and HSL expression (P<0.05) in human differentiated adipocytes. A total of 10-12-10-8 M GHRH decreased GHRH-R expression in human differentiated adipocytes (P<0.05). A total of 10-10-10-8 M GHRH increased GH and GH-R expression in human differentiated adipocytes (P<0.05). The effects of GHRH at 10-10 M on adipocyte differentiation and lipolysis were blocked when GH-R expression was silenced. CONCLUSIONS: GHRH and GHRH-R are expressed in human adipocytes and are negatively associated. GHRH at low doses may exert an anti-obesity effect by inhibiting HMSC differentiation in adipocytes and by increasing adipocyte lipolysis in an autocrine or paracrine pathway. These effects are mediated by GH and GH-R.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Changes in thyroid function with age: results from the Pizarra population-based longitudinal study.

BACKGROUND: Results of studies examining the influence of age on thyroid function and TSH levels, in the absence of thyroid disease, remain controversial. The aim of this study was to determine the course of thyroid function over 11 years in a population with normal thyroid function. METHODS: This is a population-based prospective study started in 1995-1997 (first phase), and reassessed 6 (second phase) and 11 years later (third phase). RESULTS: The TSH and FT4 in the third phase were significantly increased (p=0.001 and p=0.001, respectively), with the values being higher particularly from the age of 50 years. In those persons with a baseline TSH≥1.2 and <3 µIU/mL, the OR of having a TSH of 3-5 µIU/mL in the third phase was 6.10 (p=0.004). In those with a baseline TSH≥3 and ≤5 µIU/mL, the OR of having a TSH of 3-5 µIU/mL in the third phase was 20.8 (p<0.0001). Similar results were found for FT4. CONCLUSION: In a population free of clinical thyroid disease, TSH and FT4 values rise over the years. This increase occurs in all age groups, but depends mainly on the basal concentrations of TSH and FT4.

Resistin regulates pituitary lipid metabolism and inflammation in vivo and in vitro.

The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism.

Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance.

OBJECTIVE: Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. DESIGN: We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). RESULTS: Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. CONCLUSION: Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

MICROBIOTA INSIGHTS IN CLOSTRIDIUM DIFFICILE INFECTION AND INFLAMMATORY BOWEL DISEASE.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation that includes Crohn´s disease (CD) and ulcerative colitis (UC). Although the etiology is still unknown, some specific factors have been directly related to IBD, including genetic factors, abnormal intestinal immunity, and/or gut microbiota modifications. Recent findings highlight the primary role of the gut microbiota closely associated with a persistent inappropriate inflammatory response. This gut environment of dysbiosis in a susceptible IBD host can increasingly worsen and lead to colonization and infection with some opportunistic pathogens, especially Clostridium difficile. C. difficile is an intestinal pathogen considered the main cause of antibiotic-associated diarrhea and colitis and an important complication of IBD, which can trigger or worsen an IBD flare. Recent findings have highlighted the loss of bacterial cooperation in the gut ecosystem, as well as the pronounced intestinal dysbiosis, in patients suffering from IBD and concomitant C. difficile infection (CDI). The results of intestinal microbiota studies are still limited and often difficult to compare because of the variety of disease conditions. However, these data provide important clues regarding the main modifications and interrelations in the complicated gut ecosystem to better understand both diseases and to take advantage of the development of new therapeutic strategies. In this review, we analyze in depth the gut microbiota changes associated with both forms of IBD and CDI and their similarity with the dysbiosis that occurs in CDI. We also discuss the metabolic pathways that favor the proliferation or decrease in several important taxa directly related to the disease.

PPARgamma2 protects against obesity by means of a mechanism that mediates insulin resistance.

BACKGROUND: Many studies have focused on the physiological parameters and genetic predisposition of subjects presenting both obesity and insulin resistance (IR) and it has been suggested that the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) Pro12Ala variant may contribute to the observed variability in insulin sensitivity. We investigated whether the PPARgamma2 mRNA expression levels are associated with IR in morbid obesity in adipose and muscle tissues. MATERIALS AND METHODS: In this study, tissue biopsies were obtained from 26 morbidly obese (MO) patients and eight controls. The MO patients were divided into two groups: those with a low homeostasis model assessment of IR (HOMA-IR < 5) (MO-nonIR) and those with a high HOMA-IR (HOMA-IR > or = 8) (MO-IR). PPARgamma1, PPARgamma2 and aP2 mRNA expression levels were measured using quantitative RT-PCR. RESULTS: The study found that PPARgamma2 mRNA expression in visceral adipose tissue (VAT) was significantly lower in the MO patients (P = 0.002) than the controls. Moreover, the PPARgamma2 mRNA expression was lower in VAT (P < 0.05) and muscle tissue (P < 0.01), and higher in subcutaneous adipose tissue (SAT) (P < 0.01) in the MO-IR than the MO-nonIR group. By contrast, PPARgamma1 mRNA expression levels were not dependent on IR. Finally, the MO patients showed a significant negative correlation between PPARgamma2 mRNA expression and IR (r = -0.396, P = 0.020) in VAT and a positive correlation in SAT (r = 0.826, P < 0.001). The variable that best explained the IR was PPARgamma2 mRNA expression in SAT (P = 0.002). CONCLUSIONS: These data show that PPARgamma2 mRNA is expressed differently in the two types of MO patients and is associated with IR.

Anti-oxidized LDL antibody levels are reduced in women with hypertension.

BACKGROUND: Previous studies have suggested that hypertension may be associated with increased oxidized low-density lipoprotein (LDL). Increased in vitro oxidizability of LDL or elevated titers of anti-oxidized LDL antibodies have been shown in subjects with essential hypertension. However, the relationship between oxidized LDL and hypertension is equivocal. We examined the association between hypertension and levels of IgG anti-oxidized LDL antibodies in a group of women from the general population. MATERIALS AND METHODS: The study included 619 women classified according to their blood pressure values. IgG anti-oxidized LDL antibodies were measured by enzyme-linked immunosorbent assay and the women were classified as being above or below the 50th percentile. RESULTS: Hypertension was present in 54.3% of the women. These women had significantly lower levels of IgG anti-oxidized LDL antibodies than the normotensive women (0.280 +/- 0.117 vs. 0.336 +/- 0.125, P < 0.001). Both systolic and the diastolic blood pressures showed a significant negative correlation with the levels of IgG anti-oxidized LDL antibodies (r = -0.204, P < 0.001; r = -0.225, P < 0.001, respectively). Women with IgG anti-oxidized LDL antibody levels above the 50th percentile had a lower prevalence of hypertension than those with IgG anti-oxidized LDL antibody levels below the 50th percentile (40.2% vs. 59.8%) (P < 0.001). CONCLUSIONS: Women with hypertension had lower levels of IgG anti-oxidized LDL antibodies than normotensive women.

Use of povidone-iodine during the first trimester of pregnancy: a correct practice?

Povidone-iodine (PVP-I) has been widely used as an antiseptic agent during invasive procedures for prenatal diagnosis. Women have been reported of thyroid dysfunction after simple exposure to PVP-I. We studied the effect on thyroid function and urinary iodine excretion after a single topical application of PVP-I in 31 women who had a miscarriage during the first trimester of pregnancy. PVP-I is absorbed through the skin and the vaginal mucosa, resulting in a sudden increase in the urinary excretion of iodine and a short-term variation in concentrations of thyroid hormones in maternal serum. This metabolic effect could have consequences for the embryo and the fetus during crucial stages of development.

Anti-oxidized low-density lipoprotein antibody levels are associated with the development of type 2 diabetes mellitus.

BACKGROUND: Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We selected 391 non-diabetic women aged 18-65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile. RESULTS: Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65.1% were still OGTT-N after 6 years versus 79.5% of those who had anti-oxidized LDL antibody levels above the 50th percentile (P = 0.015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9.79 (95% confidence interval, 1.40-68.45) of developing diabetes (P < 0.001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index (P < 0.001) and the levels of anti-oxidized LDL antibodies (P = 0.042). CONCLUSIONS: Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women.

Incidence of type 2 diabetes in southern Spain (Pizarra Study).

BACKGROUND: Few European studies have used an oral glucose tolerance test (OGTT) to examine the incidence of type 2 diabetes. We determined the incidence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes in a population from southern Spain. MATERIAL AND METHODS: A population-based cohort study was undertaken in Pizarra, Spain. Baseline data were recorded on age, sex, weight, height, waist and hip circumferences, and diabetes status for 1051 persons, of whom 910 were free of type 2 diabetes (at-risk sample). Of these, 714 completed the 6-year follow-up study. Body mass index, waist-to-hip ratio and weight increase since baseline were calculated. The homeostasis model assessment equations were used to estimate the indices of insulin resistance and beta-cell function. Each person received an OGTT at baseline and after 6 years. RESULTS: Type 2 diabetes developed in 81 people for a total of 4253 person-years, representing an incidence of 19.1 cases per 1000 person-years (95% confidence interval, 15.3-23.6). Age and the presence of obesity, central obesity and carbohydrate metabolism disorders [IFG (cut off = 100 mg dL(-1), capillary blood glucose level), IGT or both] at baseline were significant markers for the onset of type 2 diabetes during follow-up. After adjusting for these variables, multivariate analysis showed weight increase, waist-to-hip ratio and the indices of insulin resistance and beta-cell function were significantly associated with the risk for type 2 diabetes. CONCLUSIONS: The incidence of type 2 diabetes in a population from southern Spain is high. It is probably associated with the high prevalence of obesity and weight increase in this population.

Different effect of laparoscopic Roux-en-Y gastric bypass and open biliopancreatic diversion of Scopinaro on serum PYY and ghrelin levels.

BACKGROUND: The impact of bariatric surgery on levels of peptide YY (PYY) and ghrelin is still under discussion. We undertook a simultaneous evaluation of the serum changes in PYY and ghrelin depending on the specific type of bariatric surgery. METHODS: Total PYY and ghrelin were analyzed in 29 healthy persons and in morbidly obese persons undergoing open biliopancreatic diversion (BPD) of Scopinaro (n = 38) or laparoscopic Roux-en-Y gastric bypass (RYGB; n = 13). RESULTS: RYGB resulted in a significantly greater loss of weight and body mass index than BPD. Both RYGB and BPD were associated with a significant increase in PYY, significantly greater for BDP (p = 0.001). Ghrelin rose significantly after RYGB (p = 0.022) but not after BPD. After surgery, PYY correlated positively with weight (r = 0.416, p = 0.009). Ghrelin did not correlate significantly with any of the variables studied. Analysis of variance showed that only the type of surgery contributed significantly to explain the variances in the PYY (p = 0.002) and ghrelin (p = 0.018). CONCLUSIONS: BPD results in a greater increase in PYY and a lower weight loss than RYGB. However, only RYGB was associated with a significant increase in ghrelin. The differing weight loss according to the type of bariatric surgery does not seem to be explained by changes arising in PYY and ghrelin.

Inverse relation between levels of anti-oxidized-LDL antibodies and eicosapentanoic acid (EPA).

Oxidative modification of LDL is thought to play an important role in the development of atherosclerosis. Susceptibility of LDL to peroxidation may partly depend on the compositional characteristics of the antioxidant and fatty acid content. The aim of this study was to examine the association between levels of antibodies to oxidized LDL and the various serum fatty acids in women. A total of 465 women aged 18-65 years were selected randomly from the adult population census of Pizarra, a town in southern Spain. Measurement of anti-oxidized-LDL was done by ELISA and the fatty acid composition of serum phospholipids was determined by GC. The levels of anti-oxidized-LDL antibodies were significantly related with age (r - 0.341, P < 0.001), BMI (r - 0.239, P < 0.001), waist:hip ratio (r - 0.285, P < 0.001), glucose (r - 0.208, P < 0.001), cholesterol (r - 0.243, P < 0.001), LDL-cholesterol (r - 0.185, P = 0.002), EPA (r - 0.159, P = 0.003), DHA (r - 0.121, P = 0.026), and the sum of the serum phospholipid n-3 PUFA (r - 0.141, P = 0.009). Multiple regression analysis showed that the variables that explained the behaviour of the levels of anti-oxidized-LDL antibodies were age (P < 0.001) and the serum phospholipid EPA (P < 0.001). This study showed that the fatty acid composition of serum phospholipids, and especially the percentage of EPA, was inversely related with the levels of anti-oxidized-LDL antibodies.

No effect of different bariatric surgery procedures on LINE-1 DNA methylation in diabetic and nondiabetic morbidly obese patients.

BACKGROUND: Bariatric surgery (BS) is proposed as a highly effective therapy for reducing weight and improving obesity-related co-morbidities. The molecular mechanisms involved in the metabolic improvement after BS are not completely resolved. Epigenetic modifications could have an important role. OBJECTIVE: The aim of this study was to evaluate the effect of different BS procedures (Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) on global DNA methylation (long interspersed nucleotide element 1 [LINE-1]) in a group of nondiabetic and diabetic severely obese patients. SETTING: University hospital, Spain. METHODS: This study included 60 patients (30 nondiabetic and 30 diabetic severely obese patients) undergoing BS: 31 patients underwent Roux-en-Y gastric bypass and 29 underwent laparoscopic sleeve gastrectomy. Before and 6 months post-BS, anthropometric data, blood pressure, and metabolic parameters were determined. LINE-1 DNA methylation was quantified by pyrosequencing. We used the methylation levels of tumor necrosis factor-α as a control gene promoter. RESULTS: There were no differences between LINE-1 methylation levels at baseline and at 6 months after surgery (66.3±1.6 versus 66.2±2.06). Likewise, there was no statistically significant difference on LINE-1 methylation levels when we stratified according to metabolic status (diabetic versus nondiabetic), nor was there regarding the BS procedure. A strong correlation was shown between LINE-1 methylation levels and weight at baseline both in diabetic and nondiabetic obese patients (r = .486; P<.001). Tumor necrosis factor-α methylation levels increased significantly after BS in the group of diabetic obese patients. CONCLUSION: After BS, global LINE-1 methylation is not modified in the short term. More studies are required to determine if LINE-1 is a stable epigenetic marker, or, on the contrary, if it is susceptible to modification by external factors such as changes in lifestyle or a surgical intervention.

Dietary fatty acids and insulin secretion: a population-based study.

OBJECTIVE: Few epidemiological studies have examined the relationship of dietary fatty acids, especially MUFA, with the interrelation between insulin secretion and insulin resistance. We assessed the relation of dietary fatty acids with insulin secretion in a free-living population. DESIGN AND SETTING: This cross-sectional, population-based study was undertaken in Pizarra, a small town in Spain. SUBJECTS AND METHODS: Anthropometrical data were collected for 1226 persons selected randomly from the municipal census, 538 of whom (randomly chosen) were given a prospective, quantitative, 7-day nutritional questionnaire. The fatty acid composition of the serum phospholipids was used as a biological marker of the type of fat consumed. Beta-cell function (betaCFI) and insulin-resistance index (IRI) were estimated by the Homeostasis Model Assessment. RESULTS: To determine which factors influence the variability of the betaCFI, we analyzed the variance of the betaCFI according to sex, the presence of carbohydrate metabolism disorders and the different components of the diet, adjusting the models for age, body mass index (BMI) and IRI. The dietary MUFA and polyunsaturated fatty acids (PUFA) contributed to the variability of the betaCFI, whereas only the proportion of serum phospholipid MUFA, but neither the saturated fatty acids nor the PUFA accounted for part of the variability of the betaCFI in a multiple regression analysis. CONCLUSION: The results of this population-based study corroborate the results of other clinical and experimental studies suggesting a favorable relationship of MUFA with beta-cell insulin secretion. SPONSORSHIP: Fondo de Investigación Sanitaria, Junta de Andalucía and the Asociación Maimónides.

Coconut oil affects lipoprotein composition and structure of neonatal chicks.

Supplementation of 10 or 20% coconut oil in the diet for 1-2 weeks produced a significant hypercholesterolemia in neonatal chicks. Plasma triacylglycerol concentration significantly increased after the addition of 20% coconut oil for 2 weeks. These results show that newborn chicks are more sensitive to saturated fatty acids from coconut oil than adult animals. The effects of this saturated fat on lipoprotein composition were studied for the first 1-2 weeks of neonatal chick life. Coconut oil supplementation in the diet (20%) for 2 weeks increased cholesterol concentration in all the lipoprotein fractions, while 10% coconut oil only increased cholesterol in low-density and very-low-density lipoproteins, an increase that was significant after 1 week of treatment. Similar results were obtained for triacylglycerol concentration after 2 weeks of treatment. Changes in phospholipid and total protein levels were less profound. Coconut oil decreased low-density and very-low-density lipoprotein fluidity, measured as total cholesterol/phospholipid ratio. Changes in esterified cholesterol/phospholipid and triacylglycerol/phospholipid ratios suggest that coconut oil affects the distribution of lipid components in the core of very-low-density particles. Likewise, the esterified cholesterol/triacylglycerol ratio was clearly increased in the low-density, and especially in the very-low-density, fraction after the first week of coconut oil feeding. Our results show that neonatal chick provides a suitable model in which to study the role of very-low-density lipoproteins in atherogenesis and the rapid response to saturated fatty acids with 12-14 carbons.

Coconut oil induces short-term changes in lipid composition and enzyme activity of chick hepatic mitochondria.

We studied the short-term effects of a 20% coconut oil supplementation to the chick diet on lipid composition of liver and hepatic mitochondria, and changes that occurred in mitochondrial-associated enzymes as a result of this diet. No significant differences were observed in the lipid contents of liver when young chicks were fed the experimental diet, whereas hepatic mitochondria rapidly changed in response to this diet. Total cholesterol significantly increased in mitochondria at 24 hours of coconut oil diet feeding and decreased when dietary treatment was prolonged for 5 to 14 days. Changes in total mitochondrial phospholipids showed an inverse profile. A significant decrease in phosphatidylethanolamine and an increase in sphingomyelin were found at 24 hours. The cholesterol/phospholipid molar ratio significantly and rapidly (24 hours) increased in mitochondria from treated animals. Cytochrome oxidase activity drastically increased after 24 hours of experimental diet feeding and lowered to the control values when dietary manipulation was prolonged for 5 to 14 days. ATPase activity showed an inverse profile. Changes in cytochrome oxidase activity were parallel to changes in the cholesterol/phospholipid molar ratio, whereas changes in ATPase activity showed an inverse correlation with changes in this molar ratio. To our knowledge, this is one of the first reports on the very rapid response (24 hours) of mitochondrial lipid composition and function to saturated fat feeding.

Differential changes in the fatty acid composition of the main lipid classes of chick plasma induced by dietary coconut oil.

For a better understanding of the hyperlipidemic function of saturated fat, we have studied the comparative effects of diet supplementation with 10 and 20% coconut oil on the main lipid classes of chick plasma. Changes in fatty acid composition of free fatty acid and triglyceride fractions were parallel to that of the experimental diet. Thus, the increase in the percentages of 12:0 and 14:0 acids may contribute to the hypercholesterolemic effects of coconut oil feeding. Plasma phospholipids incorporated low levels of 12:0 and 14:0 acids whereas 18:0, the main saturated fatty acid of this fraction, also increased after coconut oil feeding. The percentage of 20:4 n-6 was higher in plasma phospholipids than in the other fractions and was significantly decreased by our dietary manipulations. Likewise, minor increases were found in the percentages of 12:0 and 14:0 acids in plasma cholesterol esters. However, the percentage of 18:2 acid significantly increased after coconut oil feeding. Our results show a relationship between fatty acid composition of diets and those of plasma free fatty acid and triglyceride fractions, whereas phospholipids and cholesterol esters are less sensitive to dietary changes.

Effects of dietary fish oil on the fatty acid composition of the main lipid classes of chick plasma lipoproteins.

We have studied the effects of diet supplementation with 10% fish oil on fatty acid composition of the main lipid classes of chick plasma lipoproteins bearing in mind the relationship between platelet aggregation and eicosanoid production from arachidonic acid. Fish oil drastically increased the percentages of 20:5 n-3 and 22:6 n-3 acids in the high density lipoprotein lipids. The 20:5/22:6 ratio increased in triacylglycerol fraction whereas in phospholipids and cholesterol esters both 20:5 and 22:6 acids increased in a similar proportion. The percentage of arachidonic acid was higher in phospholipids than in the other lipid classes from this lipoprotein fraction and was significantly reduced by fish oil feeding. Linoleic acid, which was the most abundant fatty acid in cholesterol esters, strongly decreased after fish oil consumption. Changes induced in low- and very low density lipoproteins were similar to that observed in the high density lipoproteins. However, in the very low density lipoproteins, the 20:5/22:6 ratio was not increased in triacylglycerols, in contrast to that found in the high- and low density fractions. Our results suggest that decreases observed by fish oil feeding in the percentages of arachidonic acid in phospholipids and linoleic acid in cholesterol esters in the three lipoprotein fractions may be of importance to explain some pharmacological effects of n-3 PUFA with regard to vascular diseases.

Changes in plasma lipid composition induced by coconut oil. Effects of dipyridamole.

The comparative effects of 10-20% coconut oil feeding on fatty acid composition of the main lipid classes of chick plasma have been studied with and without simultaneous treatment with dipyridamole in order to clarify the hypolipidemic role of this drug. Coconut oil drastically increased the percentages of lauric and myristic acids in free fatty acid and triacylglycerol fractions, whereas these changes were less pronounced in phospholipids and cholesterol esters. The percentage of arachidonic acid was higher in plasma phospholipids than in the other fractions and was significantly decreased by coconut oil feeding. Linoleic acid, the main fatty acid of cholesterol esters, was drastically increased by coconut oil feeding. Changes induced by the simultaneous administration of dipyridamole were more pronounced in the phospholipids and cholesterol esters than in the other fractions. The fall observed in linoleic acid levels after dipyridamole treatment may be of interest for a lower production of its derived eicosanoids, especially in plasma phospholipids and cholesterol esters.