The postprandial inflammatory response after ingestion of heated oils in obese persons is reduced by the presence of phenol compounds.

SCOPE: Heating during the process of cooking alters the chemical properties of foods and may affect subsequent postprandial inflammation. We tested the effects of four meals rich in different oils subjected to heating on the postprandial inflammatory metabolism of peripheral blood mononuclear cells (PBMCs). METHODS AND RESULTS: Twenty obese participants received four breakfasts following a randomized crossover design, consisting of milk and muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seeds oil (SFO/canola oil) with added either dimethylpolysiloxane (SOD), or natural antioxidants from olive mill wastewater alperujo (phenols; SOP)), previously subjected to 20 heating cycles. Postprandial inflammatory status in PBMCs was assessed by the activation of nuclear NF-κB, the concentration in cytoplasm of the NF-κB inhibitor (IκB-α), the mRNA levels of NF-κB subunits and activators (p65, IKKß, and IKKα) and other inflammatory molecules (TNF-α, IL-1ß, IL-6, MIF, and JNK), and lipopolysaccharide (LPS) levels. VOO and SOP breakfasts reduced NF-κB activation, increased IκB-α, and decreased LPS plasma concentration. SFO increased IKKα, IKKß, p65, IL-1b, IL-6, MIF, and JNK mRNA levels, and plasma LPS. CONCLUSION: Oils rich in phenols, whether natural (VOO) or artificially added (SOP), reduce postprandial inflammation, compared with seed oil (sunflower).

Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state.

BACKGROUND AND AIMS: Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins (TRL). In a controlled intervention study on healthy subjects, we evaluated the influence of 3 dietary interventions, with different types of fat on postprandial TRL particle size and number. METHODS AND RESULTS: Volunteers followed three different diets for four weeks each, according to a randomized crossover design. Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); high CHO enriched with ALNA diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After a 12-h fast, volunteers consumed a breakfast with 1g fat and 7 mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets: Butter meal: 35% SFA; Olive oil meal: 36% MUFA; Walnut meal: 16% PUFA, 4% α-linolenic acid. Tryglicerides (TG) in TRL (large and small TRL) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points. The olive oil meal reduced the number of total TRL postprandial particles compared with the other meals (P=0.002). Moreover, the olive oil meal also increased the TRL particle size compared with the walnut meal (P=0.001). CONCLUSION: Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources. These novel findings have implications for understanding the postprandial lipoprotein mechanisms, and could favour the lower cardiovascular risk in Mediterranean countries.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial function in healthy men.

Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.

Monounsaturated fat-rich diet prevents central body fat distribution and decreases postprandial adiponectin expression induced by a carbohydrate-rich diet in insulin-resistant subjects.

OBJECTIVE: Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression. RESEARCH DESIGN AND METHODS: Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values <4 after an oral glucose tolerance test, and they maintained A1C <6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs). RESULTS: Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P < 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P < 0.05). CONCLUSIONS: An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects.

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men.

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN: : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

[Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications]. / La dieta mediterránea mejora la resistencia a la oxidación de las lipoproteínas de baja densidad.

UNLABELLED: Most experts, specially from Anglo-Saxon countries, recommend a low fat diet in order to prevent cardiovascular diseases. However, mortality rate by ischemic cardiopathy is low in Mediterranean countries, probably because of the consumption of a Mediterranean diet, with a high level of monounsaturated fats provided by the olive oil. We have conducted this study in order to investigate the possible influence of this kind of diet on the oxidation of LDL in vitro, the key element for the development of atherosclerosis. PATIENTS AND METHODS: 41 healthy male subjects were submitted to three consecutive 4-week diets. The first was a saturated fat-rich diet (SAT diet, 38% fat, 20% saturated). This was followed by a low fat diet (NCEP-I, 28% fat, 10% saturated) and after that a Mediterranean diet (38% fat, 22% monounsaturated fat). Plasma levels of total cholesterol, LDL-c, HDL-c, triglycerides, apolipoproteins A-I and B, -tocopherol, and the in vitro susceptibility to oxidation of LDL particles. Both hypolipidemic diets produced a significant decrease in total cholesterol, LDL-c, and apo-B plasma levels. However, it was only the NCEP-I diet that revealed a decrease in the HDL-c. The shift from a saturated fat-rich diet, or a diet rich in carbohydrates, to a Mediterranean diet increased the resistance of LDL particles to oxidation increasing the lag time period (p < 0.038), and decreasing (p < 0.001) the progression rate of the curve of oxidation of LDL. Our results point out two positive consequences of the consumption of a Mediterranean diet by healthy young males, compared with the low fat diet recommended by most Anglo-Saxon experts. On the one hand, the Mediterranean diet increases HDL-c plasma levels, and on the other hand, it decreases the susceptibility of LDL to oxidation. This is why the Mediterranean diet must be recommended in order to prevent cardiovascular diseases.

[The diet rich in monounsaturated fat modifies in a beneficial way carbohydrate metabolism and arterial pressure]. / La dieta rica en grasa monoinsaturada modifica de forma beneficiosa el metabolismo de los hidratos de carbono y la presión arterial.

OBJECTIVE: Two dietary regimens recommended for the reduction of coronary risk, by way of their effects on lipid profile, are the diet low in saturated fat and a diet rich in monounsaturated fats (MUFA). However the effects of these diets on carbohydrate metabolism in healthy subjects are not well known. The objective of this study was to compare the effect of both diets on various parameters of carbohydrate metabolism. METHODS: 41 healthy young males were submitted to 3 consecutive diets, each for a duration of 4 weeks. The first diet was rich in saturated fat (SAT) (38% fat, 20% saturated). The second was rich in carbohydrates following the recommendations of the NCEP-I (National Cholesterol Education Program type I) (28% fat, 47% carbohydrates). The last one was a diet rich in monounsaturated fatty acids (38% fat, 22% MUFA). At the end of each dietary period, blood pressure (BP) and blood levels of glucose, insulin and free fatty acids were determined. 29 subjects were also submitted to an oral glucose tolerance test (OGTT) at the end of each diet. RESULTS: The SAT diet induced the highest levels of insulin after the OGTT. The consumption of the MUFA diet determined the lowest levels of fasting blood glucose (-0.60 mmol/l [13%], p < 0.0002), insulin (-9 microUl/ml [47%], p < 0.0002) and free fatty acids (-0.11 mmol/l [24%], p = 0.006), compared to the NCEP-I diet. Systolic and diastolic blood pressure were higher in the NCEP-I diet than during the other periods (SBP: +6 mmHg compare with SAT [5%], p = 0.0001; and +5 mmHg compare with MUFA [4%], p = 0.0001; DBP: +20 mmHg compare with MUFA [27%], p = 0.0001) and +6 mmHg compared with SAT [8%], p = 0.0001). CONCLUSION: Of the diets most commonly used for the treatment and prevention of arteriosclerosis, a diet rich in monounsaturated fats is the most beneficial for the healthy population from the point of view of carbohydrate metabolism and blood pressure.

Plasma lipid response to hypolipidemic diets in young healthy non-obese men varies with body mass index.

Lipid response to dietary fat is highly variable among individuals of a population. The aim of this study was to establish whether being overweight is one of the factors that determines this response. Forty-one non-obese healthy men were divided into two groups according to body mass index as follows: controls, <25 kg/m2; overweight, >25 kg/m2 but <30 kg/m2. After consuming a saturated fat-rich diet (SAT diet: 38% fat, 20% saturated) for 4 wk, subjects were switched to a low fat diet [National Cholesterol Education Program (NCEP)-I diet: 28% fat, 10% saturated] for 4 wk and then to a monounsaturated fat-rich diet (MUFA diet: 38% fat, 22% monounsaturated) for 4 wk. Data were analyzed by Student's t test and two-way ANOVA for repeated measures. After consuming the NCEP-I diet, the overweight subjects had a smaller decrease relative to the SAT diet period in plasma total cholesterol [-0.30 vs. -0.67 mmol/L (-7 vs. -16%), P < 0.02] and low density lipoprotein-cholesterol concentrations [-0.24 vs. -0.55 mmol/L (-9 vs. -21%), P < 0.04] than controls. However, in the overweight subjects, the MUFA diet produced a greater decrease in plasma triglycerides than in the controls relative to the SAT diet period [-0.36 vs. -0.03 mmol/L (-26 vs. -4%), P < 0.006] and to the NCEP-I diet period [-0.29 vs. 0. 01 mmol/L (-22 vs. 1%), P < 0.01). Plasma cholesterol concentrations changed to a lesser extent, and triglyceride concentration to a greater extent, in overweight but non-obese young men than in those of normal weight in response to changes in dietary fat composition. Our data suggest that in the diet treatment of obese hyperlipemic subjects, it is more important for them to lose weight than to change the fat composition of their diets.

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Composition of human VLDL triacylglycerols after ingestion of olive oil and high oleic sunflower oil.

This work was undertaken to determine the effect of diets enriched with olive oil or high oleic sunflower oil on very low density lipoprotein (VLDL) triacylglycerol composition of healthy human subjects. Both oils contain a similar proportion of monounsaturated fatty acids (MUFA) but differ in their triacylglycerol composition. All 22 human subjects initially consumed a low fat, high carbohydrate diet as recommended by the National Cholesterol Education Program (NCEP-I). They then consumed the two experimental oils (40% dietary energy) in a crossover design. The olive oil and high oleic sunflower oil diets resulted in significant increases in palmitoleic (55%, P < 0.05), oleic (27%, P < 0.01) and eicosenoic (>100%, P < 0.001) acids of VLDL triacylglycerols, whereas there was a significant decrease in linoleic acid (38%, P < 0.001). In addition, the high oleic sunflower oil diet increased the content of stearic acid (60%, P < 0.05) and total saturated fatty acids (14%, P < 0.05). Both MUFA-rich diets significantly (P < 0.01) decreased the content of sn-glycerol-palmitate-linoleate-oleate, sn-glycerol-palmitoleate-dioleate and sn-glycerol-palmitate-dilinoleate in VLDL with regard to the NCEP-I diet, whereas they increased the content of sn-glycerol-trioleate (>100%, P < 0.001 after the olive oil diet; 80%, P < 0.05 after the high oleic sunflower oil diet). Intake of olive oil, in particular, significantly decreased the content of sn-glycerol-tripalmitate (36%, P < 0.01) and increased the content of dioleoyl-containing triacylglycerols. MUFA (P < 0.01) and arachidonic acid (P < 0.001) tended to be rich in the sn-2 position of VLDL triacylglycerols during the periods of consuming the olive oil or high oleic sunflower oil diets. In addition, olive oil, but not high oleic sunflower oil, further contributed to VLDL triacylglycerols that contained alpha-linolenic and docosahexaenoic acids acylated in the sn-2 position. These data suggest that differences in the composition of VLDL triacylglycerols may be of major importance in explaining the beneficial effects of dietary olive oil in reducing the atherogenic risk profile in healthy subjects.

Lipoprotein concentrations in normolipidemic males consuming oleic acid-rich diets from two different sources: olive oil and oleic acid-rich sunflower oil.

The effects on plasma lipid concentrations of two oleic acid-rich diets, prepared with two different plant oils--olive oil and sunflower oil high in monounsaturated fatty acids (MUFAs)-- were compared with a National Cholesterol Education Program (NCEP) I diet. Twenty-one healthy, normolipidemic, young males consumed an NCEP-I diet (30% of energy as fat) during a 25-d period. Subjects were then assigned to two 4-wk study periods, according to a randomized, crossover design. Group one was placed on an olive oil-enriched diet (40% fat, 22% MUFAs), followed by a 4-wk period of a sunflower oil-enriched diet (40% fat, 22% MUFAs). In group two, the order of the diets was reversed. Both MUFA dietary periods resulted in an increase in high-density-lipoprotein (HDL) cholesterol (7% for the olive oil diet and 4% for the sunflower oil diet) and in apolipoprotein (apo) A-I (9% for both) compared with the NCEP-I diet. Low-density-lipoprotein (LDL) cholesterol and apo B concentrations (x +/- SEM) were lower (P < 0.05) during the sunflower oil diet (2.40 +/- 0.11 mmol/L, 0.85 +/- 0.04 mg/L) than during the olive oil diet (2.64 +/- 0.15 mmol/L, 0.93 +/- 0.05 mg/L). No significant differences were observed in these variables between the sunflower oil and NCEP-I (2.48 +/- 0.13 mmol/L, 0.89 +/- 0.04 mg/L) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic acinar cell function and morphology in rats fed zinc-deficient and marginal zinc-deficient diets.

The prevalence of marginal zinc nutriture in several populations of people in this country and the lack of reports on the effect of marginal zinc nutriture in experimental animals prompted us to look at pancreatic acinar cell function and morphology in rats fed a zinc-deficient diet ad libitum: 4 and 50 ppm zinc-supplemented diets in amounts isocaloric to a zinc-deficient diet and Rodent-Blox fed ad libitum for a period of 49 +/- 1 (SEM) days. Because of a diminished rate of energy expenditure in zinc-deficient rats, animals receiving 50 ppm zinc-supplemented diets were offered less food, resulting in decreased body weight and pancreas weight, DNA, RNA, total protein, lipase, amylase, and secretion of protein. Specific changes due to zinc deficiency included (a) further decrease in body weight and (b) increase in content, specific activity, and secretion of lipase. Both the size and volume fraction of zymogen granules were reduced in zinc deficiency. The lumina of acinar and small ducts were collapsed with paucity of secretion products. Zinc deficiency may therefore lead to a defect in discharge mechanism. A further reduction in volume fraction of zymogen granules in the 4 ppm zinc-supplemented group was associated with increased secretion of serine proteases (trypsinogen and chymotrypsinogen), which constitute approximately 46% of total secretory protein in the pancreas under normal dietary conditions. This indicated an accelerated discharge due to an unknown mechanism. Changes in the secretion of digestive enzymes in the present study simulated ethanol-induced secretory alterations that were previously observed. Because abnormal zinc nutriture and chronic alcoholism are commonly associated, it is speculated that zinc deficiency may play a role in the ethanol-induced secretory alterations.

Interaction between marginal zinc deficiency and chronic alcoholism: pancreatic structure and function in rats in vitro.

The present study was done to determine interaction of ethanol and marginal zinc nutriture on morphology and function of rat pancreas. Sprague-Dawley rats were maintained on Wayne Rodent-Blox ad libitum; marginal zinc-deficient diet plus ethanol ad libitum and pair fed with animals fed marginal zinc-deficient liquid diet and zinc-supplemented liquid diet with ethanol for 33 (+/- 1 SEM) days. Body, pancreas, liver, heart, and kidney weights were determined, and studies of pancreatic DNA, RNA, total proteins and newly labeled proteins, amylase, lipase, trypsinogen, and chymotrypsinogen were done on pancreatic lobules in vitro. Ethanol feeding independent of the zinc content of the diet caused a decrease in zinc content of the liver, body weight, liver and pancreas weight, pancreatic DNA, total protein, and amylase concentration and an increase in lipase and trypsinogen concentrations and in secretion of amylase and lipase. Interaction of the marginal zinc diet and ethanol feeding resulted in a decreased synthesis of RNA and secretion of newly synthesized protein and an increase in secretion of serine proteases. Morphological studies revealed a reduction in the number of zymogen granules in animals fed low levels of zinc, also with an accumulation of lipid droplets when the diet contained ethanol. These studies confirmed our previous observations of specific injury to the pancreas due to marginal zinc nutriture or to ethanol, independent of each other. Marginal zinc nutriture in concert with ethanol resulted in impaired RNA synthesis and secretion of nascent proteins and increased secretion of serine proteases. These data indicate that altered zinc metabolism induced by ethanol per se may contribute to ethanol-induced disturbance of pancreatic function.