Skeletal Muscle Phospholipids Research Articles

Fatty acid profile of skeletal muscle phospholipid is altered in mdx mice and is predictive of disease markers

The mdx mouse is a model for Duchenne muscular dystrophy. The fatty acid (FA) composition in dystrophic muscle could potentially impact the disease severity. We tested FA profiles in skeletal muscle phospholipid (PL) and triglyceride in mdx and control (con) mice to assess associations with disease state as well as correlations with grip strength (which is lower in mdx) and serum creatine kinase (CK, which is elevated in mdx). Compared with con, mdx PL contained less docosahexaenoic acid (P < .001) and more linoleic acid (P = .001). Docosahexaenoic acid contents did not correlate with strength or serum CK. Linoleic acid content in PL was positively correlated with CK in mdx (P < .05) but not con. α-Linolenic acid content in PL was positively correlated with strength in mdx (P < .05) but not con. The FA profile in triglyceride showed less difference between groups and far less predictive ability for disease markers. We conclude that profiling the FA composition of tissue lipids (particularly PL) can be a useful strategy for generating novel biomarkers and potential therapeutic targets in muscle diseases and likely other pathological conditions as well. Specifically, the present results have indicated potential benefits of raising content of particular n-3 FAs (especially α-linolenic acid) and reducing content of particular n-6 FAs (linoleic acid) in PL of dystrophic muscle.

Altered fatty acid composition of skeletal muscle phospholipid in mdx mice

Mdx mice are a model for Duchenne muscular dystrophy (DMD) and exhibit increased oxidative stress and inflammation. We sought to determine if the profile of fatty acids (FAs) in muscle phospholipid (PL) is altered in manners that could impact anti-inflammatory status or other aspects of muscular function. 8 mdx mice and 8 C57BL/10 control mice (con), on the same standard diet, were tested with a grip strength meter and then skeletal muscle was collected. The FA profile of quadriceps PL was determined by HPLC, assessing the abundance of 22 FAs as percentage of total FAs in PL. Compared to con, mdx PL contained less of the ω-3 FA docosahexaenoic acid (DHA) (20.3±1.2% vs. 24.0±1.8%, P<0.05) and more linoleic acid (13.4±0.5% vs. 11.7±0.9%, P<0.05). Mdx PL also contained more oleic acid (6.1±1.2% vs. 3.4±0.4%, P<0.05) with no significant difference for stearic acid; thus, Δ-9 desaturase activity may have been accentuated in mdx mice. In addition, α-linolenic acid content in PL was positively correlated with muscular strength in mdx mice (R=0.83, P<0.05) but not in control mice (R=−0.66, P=0.08), indicating a potential benefit of ω-3 FAs to diseased muscle. In conclusion, ω-3 FAs in muscle could be of importance for coping with the disease process in DMD. Furthermore, we discovered potential evidence for altered desaturase activity that requires further study to indicate a physiological role. Supported by Rutgers University

Separation of positional and geometrical fatty acid isomers as 2-nitrophenylhydrazide derivatives by high-performance liquid chromatography

Previously, following derivatization to their 2-nitrophenylhydrazide (2-NPH) derivatives, fatty acid (FA) abundances have been evaluated using high-performance liquid chromatography (HPLC). Although the method was sensitive, resolution was insufficient for many of the biologically important FAs. We have developed an enhanced separation of 24 FAs by use of different column temperature, stationary phase, and mobile phase gradient conditions. We applied this method to analysis of mouse skeletal muscle phospholipid and triglyceride. This further development of the chromatographic separation of 2-NPH FAs may lead to greater utility of this HPLC approach.

Жирнокислотний склад фосфоліпідів плазми крові, печінки і скелетних м’язів щурів за експериментальної гіперхолестеринемії та впливу риб’ячого жиру

Fatty acid composition of phospholipids which are the main structural elements of the cytoplasmic and cell membranes studied. It was established that in the fatty acid composition of blood plasma, liver, skeletal muscles phospholipids in rats with experimental hyperсholesterinemia an increase in saturated fatty acids with even and odd number of carbon atoms in chain and monounsaturated fatty acids of family n-9 took place. However, the relative content of polyunsaturated fatty acids of families n-3 and n-6 decreased. Inverse patterns due to the above fatty acids in fatty acid composition of blood plasma, liver, skeletal muscles phospholipid in rats with experimental hypercholesterinemia corrected by fish oil. It decreased the relative content of saturated fatty acids with even and odd number of carbon atoms in chain and monounsaturated fatty acids of family n-9, and increased the relative content of polyunsaturated fatty acids of families n-3 and n-6. Feeding with fish oil corrected fatty acid composition of blood plasma, liver and skeletal muscle phospholipids in rats with experimental hypercholesterolemia. Keywords: fatty acid composition, phospholipids, experimental hiperсholeste­rinemia, fish oil, rats.

The Effect of Exercise on the Skeletal Muscle Phospholipidome of Rats Fed a High-Fat Diet

The aim of this study was to examine the effect of endurance training on skeletal muscle phospholipid molecular species from high-fat fed rats. Twelve female Sprague-Dawley rats were fed a high-fat diet (78.1% energy). The rats were randomly divided into two groups, a sedentary control group and a trained group (125 min of treadmill running at 8 m/min, 4 days/wk for 4 weeks). Forty-eight hours after their last training bout phospholipids were extracted from the red and white vastus lateralis and analyzed by electrospray-ionization mass spectrometry. Exercise training was associated with significant alterations in the relative abundance of a number of phospholipid molecular species. These changes were more prominent in red vastus lateralis than white vastus lateralis. The largest observed change was an increase of ~30% in the abundance of 1-palmitoyl-2-linoleoyl phosphatidylcholine ions in oxidative fibers. Reductions in the relative abundance of a number of phospholipids containing long-chain n-3 polyunsaturated fatty acids were also observed. These data suggest a possible reduction in phospholipid remodeling in the trained animals. This results in a decrease in the phospholipid n-3 to n-6 ratio that may in turn influence endurance capacity.

Conjugated Linoleic Acid Isomers, t10c12 and c9t11, are Differentially Incorporated into Adipose Tissue and Skeletal Muscle in Humans

Conjugated linoleic acid (CLA) is a popular supplement believed to enhance immune function, body composition and insulin sensitivity, but results of scientific studies investigating its effects are conflicting. The isomer- and tissue-specific effects of CLA may explain these conflicting results. Therefore, this study quantified the incorporation of the c9t11 and t10c12 CLA isomers into adipose tissue and skeletal muscle in response to supplementation in healthy, regularly-exercising, non-obese persons. The CLA group (n = 14) ingested 3.9 g per day CLA (50:50 t9c11:c10t12) and the placebo group (n = 11) 3.9 g per day high-oleic-acid sunflower oil for 12 weeks. Following supplementation, the t10c12 isomer was incorporated into adipose tissue triacylglycerol (P < 0.001), and the c9t11 isomer tended to increase in skeletal muscle phospholipids (P = 0.056). Therefore, human adipose tissue and skeletal muscle are enriched with CLA in an isomer-specific manner.

Membrane fatty acid composition of rat skeletal muscle is most responsive to the balance of dietaryn-3 andn-6 PUFA

The present study quantifies the relationships between diet fatty acid profile and fatty acid composition of rat skeletal muscle phospholipids. Young adult male Sprague-Dawley rats were fed, for 8 weeks, on one of twelve moderate-fat diets (25 % of total energy) differing only in fatty acid profile. SFA content ranged from 8-88 % of total fatty acids, MUFA 6-65 %, total PUFA 4-81 %, n-6 PUFA 3-70 % and n-3 PUFA 1-70 %. Diet PUFA included only essential fatty acids 18 : 2n-6 and 18 : 3n-3. The balance between n-3 and n-6 PUFA (PUFA balance) in the diet ranged from 1 : 99 to 86 : 14 % n-3 PUFA:n-6 PUFA. The slope of muscle phospholipid composition plotted against diet composition quantifies the response of muscle membrane composition to dietary fat (0, no response; 1, complete conformity with diet). The resulting slopes were 0.02 (SFA), 0.10 (PUFA), 0.11 (MUFA), 0.14 (n-3 PUFA) and 0.23 (n-6 PUFA). The response to PUFA balance was biphasic with a slope of 0.98 below 10 % diet PUFA balance and 0.16 above 10 %. Thus, low diet PUFA balance has greater influence on muscle composition than 18-carbon n-3 or n-6 PUFA individually. Equations provided may allow prediction of muscle composition for other diet studies. Diet PUFA balance dramatically affects muscle 20 : 4n-6 and 22 : 6n-3. This may have significant implications for some disease states in human subjects.

Skeletal muscle structural lipids improve during weight-maintenance after a very low calorie dietary intervention

BackgroundThe objective was to investigate in a group of obese subjects the course in skeletal muscle phospholipid (SMPL) fatty acids (FA) during a 24-weeks weight maintenance program, which was preceded by a successful very low calorie dietary intervention (VLCD). Special focus was addressed to SMPL omega-3 FA, which is a lipid entity that influences insulin action.MethodsNine obese subjects (BMI = 35.7 ± 1.0 kg/m2), who had completed an 8 weeks VLCD (weight-loss = -9.7 ± 1.6 kg, P < 0.001), had obtained skeletal muscle biopsies (vastus lateralis) before and after a dietician-guided 24-weeks weight-maintenance program (-1.2 ± 1.5 kg, P = ns). SMPL FA composition was determined by gas liquid chromatography. During the preceding VLCD, insulin sensitivity (HOMA-IR) and glycemic control (HbA1c) improved but no change in SMPL omega-3 FA was observed. During the weight-maintenance program five subjects received the pancreas lipase inhibitor Orlistat 120 mg t.i.d. versus placebo.ResultsHOMA-IR and HbA1c stabilized and SMPL total omega-3 FA, docosahexaenoic acid and ratio of n-3/n-6 polyunsaturated FA increased by 24% (P < 0.01), 35% (P < 0.02) and 26% (P < 0.01), respectively, whereas saturated and monounsaturated FA did not change. Plasma total-cholesterol and LDL-cholesterol, which decreased during the VLCD, reverted to pre-VLCD levels (P < 0.01). Orlistat therapy was associated with weight-loss (P < 0.05), trends for better glycemic control (P = 0.15) and greater increase in SMPL docosahexaenoic acid (P = 0.12) but similar reversal of plasma cholesterols compared to placebo.ConclusionThe data are consistent with the notion that greater SMPL omega-3 FA obtained during a weight-maintenance program may play a role for preserving insulin sensitivity and glycemic control being generated during a preceding VLCD.

Sex and muscle structural lipids in obese subjects – an impact on insulin action?

Long-chain polyunsaturated fatty acid (LCPUFA) especially the n-3-FA of skeletal muscle phospholipids may facilitate insulin action, whereas saturated and trans-FA act oppositely. Community studies show that non-diabetic weight matched obese men and women display similar insulin resistance, despite the fact that an android fat distribution is detrimental to insulin action. The increased extramyocellular fat mass of obese women may act in a paracrine manner such that its release of free FA and cytokines may hamper in situ desaturation and elongation of FA in skeletal muscle phospholipids. To test the hypothesis that obese women may display an inferior FA composition compared to obese men, the FA composition of skeletal muscle phospholipids was determined in vastus lateralis biopsies obtained from 12 non-diabetic obese women with a typical gynoid fat distribution, nine non-diabetic obese men with a typical android fat distribution and 12 (seven females) lean age matched healthy controls (body mass index 34.6 +/- 1.0 kg m(-2), 36.5 +/- 1.2 and 22.5 +/- 0.5; age 47 +/- 2 years, 51 +/- 3 and 49 +/- 2). Obese women displayed decreased LCPUFA n-3 and ratio of n-3/n-6 PUFA, whereas trans-FA and palmitic-FA (C16 : 0) were increased compared to obese men and controls (all Ps < 0.05). Plasma high-density lipoprotein cholesterol (HDL-C), triglycerides and a marker of insulin sensitivity were similar between obese women and men but impaired compared to controls (Ps < 0.05). The data support the hypothesis that insulin resistant non-diabetic obese men display a more optimal skeletal muscle phospholipid FA composition than their female counterparts, which may be a mechanism to compensate the detrimental effect on insulin action of an android fat distribution.

Arachidonic Acid Content in Adipose Tissue Is Associated With Insulin Resistance in Healthy Children

The fatty acid composition of membrane structural lipids, which is partly dependent on dietary intake, is associated with insulin action. To examine the association between fatty acid composition of adipose tissue and skeletal muscle phospholipids with insulin resistance markers in a healthy pediatric population. Using a cross-sectional design, we studied 83 healthy children divided into 3 groups, ages 2 to 5, 6 to 10 and more than 10 years. Fatty acid composition of adipose tissue triacylglycerols and skeletal muscle phospholipids, plasma lipid profile and fasting plasma levels of glucose and insulin were measured. There was a linear increase of insulinemia, glycemia and homeostasis adipose tissue model assessment (HOMA) index throughout the pediatric age range. Linoleic acid proportion in skeletal muscle and arachidonic acid proportion in adipose tissue also increased significantly with age. An age-independent positive correlation between insulinemia or HOMA index and arachidonic acid content in adipose tissue triacylglycerols (r = 0.47, P < 0.001) was found. An age-dependent negative correlation was present between insulinemia or HOMA index and oleic acid content in skeletal muscle phospholipids (r = -0.30, P = 0.03 and r = -0.28, P < 0.04, respectively). Trans fatty acids content did not correlate with any marker of insulin resistance. Healthy children present a prepubertal increase of insulin resistance, which is significantly correlated with arachidonic acid content in adipose tissue.

Effect of L‐Carnitine on Skeletal Muscle Lipids and Oxidative Stress in Rats Fed High‐Fructose Diet

There is evidence that high-fructose diet induces insulin resistance, alterations in lipid metabolism, and oxidative stress in rat tissues. The purpose of this study was to evaluate the effect of L-carnitine (CAR) on lipid accumulation and peroxidative damage in skeletal muscle of rats fed high-fructose diet. Fructose-fed animals (60 g/100 g diet) displayed decreased glucose/insulin (G/I) ratio and insulin sensitivity index (ISI0,120) indicating the development of insulin resistance. Rats showed alterations in the levels of triglycerides, free fatty acids, cholesterol, and phospholipids in skeletal muscle. The condition was associated with oxidative stress as evidenced by the accumulation of lipid peroxidation products, protein carbonyls, and aldehydes along with depletion of both enzymic and nonenzymic antioxidants. Simultaneous intraperitoneal administration of CAR (300 mg/kg/day) to fructose-fed rats alleviated the effects of fructose. These rats showed near-normal levels of the parameters studied. The effects of CAR in this model suggest that CAR supplementation may have some benefits in patients suffering from insulin resistance.

Effect of Amiodarone on Phospholipid Content and Composition in Heart, Lung, Kidney and Skeletal Muscle: Relationship to Alteration of Thyroid Function

To investigate the effect of chronic amiodarone treatment on tissue phospholipids, a marker of amiodarone-induced toxicity, and to test the hypothesis that tissue phospholipids changes are related to amiodarone-induced effects on thyroid function, male Wistar rats were treated with amiodarone and tissue phospholipid content and fractions were assessed. Twenty-six animals were allocated to 4 groups: (i) group 1 received amiodarone, 20 mg/kg per day, for 3 weeks (n = 6); (ii) group 2 received amiodarone for 5 weeks (n = 6); (iii) group 3 received drug for 6 weeks (n = 6), and (iv) group 4 (control group) received the diluent for 6 weeks (n = 8). Total phospholipid content of lung, kidney and skeletal muscle but not heart was increased after 3 weeks of amiodarone treatment. With longer durations of treatment, the phospholipid content was significantly (p < 0.05) reduced in all four organs. The proportion of phospholipids in different classes was modified by amiodarone treatment with the most consistent changes across different tissues being reductions in phosphatidylethanolamine and increases in phosphatidylserine. Serum thyroxine concentration was significantly (p < 0.05) reduced at 5 weeks of treatment and thereafter. There was a significant correlation between serum thyroxine and total phospholipid concentration in heart (r = 0.555; p < 0.05) and lung (r = 0.502; p < 0.05). For heart, there was a significant correlation between serum thyroxine and the distribution of phospholipid classes, mainly for phosphatidylserine even after considering amiodarone dose. The same was found in the lung. In the kidney and skeletal muscle, there was a significant (p < 0.05) correlation between serum thyroxine and the proportion of phospholipids in phosphatidylcholine and sphingomyelin. In conclusion, this study presents the novel finding of a biphasic tissue phospholipid response to amiodarone characterized by a short term increase in phospholipids in lung, kidney and skeletal muscle but not the heart followed by a long term decline in phospholipids in all four organs that is likely due to a direct action of amiodarone on phospholipid metabolism and potentially the result of amiodarone-induced reduction in thyroid function.

Fatty acid composition of skeletal muscle and adipose tissue in Spanish infants and children

There is a relationship between the fatty acid profile in skeletal muscle phospholipids and peripheral resistance to insulin in adults, but similar data have not been reported in infancy and childhood. The objective of this study was to investigate the fatty acid composition of skeletal muscle and adipose tissue across the paediatric age range. The fatty acid profile of skeletal muscle phospholipids and adipose tissue triacylglycerols was analysed in ninety-three healthy Spanish infants and children distributed into four groups: group 1 (0 to <2 years, n 10); group 2 (2 to <5 years, n 41); group 3 (5 to <10 years, n 24); group 4 (10 to 15 years, n 18). In skeletal muscle phospholipids, oleic acid (18: 1n-9cis) content decreased significantly whereas that of linoleic (18: 2n-6) acid increased significantly with age (P for trend <0.01). In adipose tissue, the contents of triacylglycerol and linoleic acid increased significantly across the paediatric age range (P for trend <0.01), whereas dihomo-gamma-linolenic (20: 3n-6) and arachidonic (20: 4n-6) showed significant differences between groups. The variations in fatty acid composition observed with age indicated an imbalance in dietary n-3/n-6 long-chain PUFA.

Regular transcutaneous myostimulation alters skeletal muscle phospholipid fatty acid composition and oxidative stability in rabbits.

This experiment was performed to study the effects of regular, isometric, electrically induced contractions on skeletal muscle phospholipid (PL) and triglyceride (TG) fatty acid profile and oxidative stability. Transcutaneous electrical myostimulation of lo ngissimus dorsi (30 Hz, 20 ms impulse length, 10 mA, for 2 ×20 min daily) was performed on 8 Pannon White male rabbits for 4 weeks; 8 animals were set as control. Muscle TG and PL fatty acid profiles were determined by capillary gas chromatography after lip id fractionation. In the PL, the proportion of pentadecanoic (C15:0), palmitic (C16:0), linoleic (C18:2 n -6) and γ-linolenic (C18:3 n -6) acids decreased significantly compared to the control, as well as the sum of total saturated fatty acids. Increasing pr oportions of palmitoleic (C16:1 n-7), gondoic (C20:1 n -9), arachidonic (C20:4 n -6), eicosapentaenoic (C20:5 n -3) and docosahexaenoic (C22:6 n -3) acids were measured. The C20:4 n -6/C20:3 n -6 ratio (estimated Δ5 desaturase activity), the sum of polyunsaturat ed fatty acids (PUFA) of 20 to 22 carbon chain length, the sum of total n -6 fatty acids and the unsaturation index increased. In the TG, stearic acid (C18:0) proportion was significantly decreased by the stimulation. Electrical treatment increased oxidativ e stability as assessed by thiobarbituric acid reactive substances (TBARS).

Exercise alters the profile of phospholipid molecular species in rat skeletal muscle.

We have determined the effect of two exercise-training intensities on the phospholipid profile of both glycolytic and oxidative muscle fibers of female Sprague-Dawley rats using electrospray-ionization mass spectrometry. Animals were randomly divided into three training groups: control, which performed no exercise training; low-intensity (8 m/min) treadmill running; or high-intensity (28 m/min) treadmill running. All exercise-trained rats ran 1,000 m/session for 4 days/wk for 4 wk and were killed 48 h after the last training bout. Exercise training was found to produce no novel phospholipid species but was associated with significant alterations in the relative abundance of a number of phospholipid molecular species. These changes were more prominent in glycolytic (white vastus lateralis) than in oxidative (red vastus lateralis) muscle fibers. The largest observed change was a decrease of approximately 20% in the abundance of 1-stearoyl-2-docosahexaenoyl-phosphatidylethanolamine [PE(18:0/22:6); P < 0.001] ions in both the low- and high-intensity training regimes in glycolytic fibers. Increases in the abundance of 1-oleoyl-2-linoleoyl phopshatidic acid [PA(18:1/18:2); P < 0.001] and 1-alkenylpalmitoyl-2-linoleoyl phosphatidylethanolamine [plasmenyl PE (16:0/18:2); P < 0.005] ions were also observed for both training regimes in glycolytic fibers. We conclude that exercise training results in a remodeling of phospholipids in rat skeletal muscle. Even though little is known about the physiological or pathophysiological role of specific phospholipid molecular species in skeletal muscle, it is likely that this remodeling will have an impact on a range of cellular functions.

Effect of chronic wheel running on the fatty acid composition of phospholipids and triacylglycerols in rat serum, skeletal muscle and heart.

The purpose of this study was to examine the effects of long-term wheel running on the fatty acid composition of phospholipids (PL) and triacylglycerols (TG) in rat serum, skeletal muscle (soleus and extensor digitorum longus) and heart. To this end, the relevant tissues of 11 trained male Wistar rats were compared with those of 14 untrained ones. There were several significant differences between the two groups regarding the concentrations and percentages of individual fatty acids in serum PL and TG, with most differences appearing in the fatty acid distribution of PL. Monounsaturated fatty acids of muscle PL were significantly lower in the trained rats. Estimated elongase activity was significantly higher, whereas Delta(9)-desaturase activity was significantly lower in the trained muscles. Monounsaturated fatty acids of PL were also significantly lower in the trained hearts. The fatty acid composition of PL in the skeletal muscles and the heart adapted to training in a comparable manner, whereas most of the changes in the fatty acid profile of TG were tissue-dependent. Judging from the magnitude of the effect sizes and the percentage differences between trained and untrained animals, there were many large effects of chronic exercise on the fatty acid composition of the tissues examined. Long-term wheel running modified the fatty acid profile of PL and TG in rat serum, skeletal muscle and heart, and could thus be considered as a modulator of tissue fatty acid composition.

Effect of α‐Lipoic Acid on Lipid Profile in Rats Fed a High‐Fructose Diet

This study investigated the effect of administration of α-lipoic acid (LA) on lipid metabolism in high fructose–fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.

Fatty acid composition of skeletal muscle reflects dietary fat composition in humans

It is still unknown whether the fatty acid composition of human skeletal muscle lipids is directly influenced by the fat composition of the diet. We investigated whether the fatty acid composition of the diet is reflected in the fatty acid profile of skeletal muscle phospholipids and triacylglycerols. Thirty-two healthy adults (25 men and 7 women) included in a larger controlled, multicenter dietary study were randomly assigned to diets containing a high proportion of either saturated fatty acids (SFAs) [total fat, 36% of energy; SFAs, 18% of energy; monounsaturated fatty acids (MUFAs), 10% of energy] or MUFAs (total fat, 35% of energy; SFAs, 9% of energy; MUFAs, 19% of energy) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish oil capsules [containing 3.6 g n-3 fatty acids/d; 2.4 g eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)] or placebo. A muscle biopsy sample was taken from the vastus lateralis muscle after the diet period. Parallel analyses of diet and supplementation effects were performed. The proportions of myristic (14:0), pentadecanoic (15:0), heptadecanoic (17:0), and palmitoleic (16:1n-7) acids in the skeletal muscle phospholipids were higher and the proportion of oleic acid (18:1n-9) was lower in the SFA group than in the MUFA group. The proportion of total n-3 fatty acids in the muscle phospholipids was approximately 2.5 times higher, with a 5 times higher proportion of eicosapentaenoic acid (20:5n-3), in subjects supplemented with n-3 fatty acids than in those given placebo. Similar differences were observed in the skeletal muscle triacylglycerols. The fatty acid composition of skeletal muscle lipids reflects the fatty acid composition of the diet in healthy men and women.

Desaturation and elongation of Fatty acids and insulin action.

Insulin resistance is characterized by specific changes of the composition of fatty acids in the serum lipids and in the skeletal muscle membranes. Impaired insulin sensitivity is associated with high proportions of palmitic (16:0) acid and low levels of linoleic (18:2 n-6) acid in serum. In addition, there are apparent changes of the fatty acid desaturase activities, suggesting an increased activity of the Delta9 and Delta6 desaturases and a decreased activity of the Delta5 desaturase. The activity of the fatty acid desaturases is regulated by long-chain polyunsaturated fatty acids and insulin and is probably also dependent on the degree of physical activity. A high ratio between arachidonic (20:4 n-6) and dihomo-gamma linolenic (20:3 n-6) acid, as a measure of Delta5 desaturase activity, in the skeletal muscle phospholipids has been related to good insulin sensitivity. Available knowledge seems to indicate that the degree of saturation of the body lipids, and especially the proportion of palmitic acid in the lipid membranes, may be critical for insulin sensitivity. The strong relationships between the Delta5 desaturase activity, a high content of long-chain polyunsaturated fatty acids in the skeletal muscle, and insulin sensitivity may be due to parallel effects of diet and/or physical activity on the fatty acid composition and on insulin sensitivity.

Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans

A polymorphism in FABP2 that results in an alanine-to-threonine substitution at amino acid 54 of the intestinal fatty acid-binding protein (IFABP) is associated with insulin resistance in Pima Indians. In vitro, the threonine form (Thr54) has a higher binding affinity for long-chain fatty acids than does the alanine form (Ala54). We tested whether this polymorphism affected metabolic responses to dietary fat, in vivo. Eighteen healthy Pima Indians, half homozygous for the Thr54 form of IFABP and half homozygous for the Ala54 form, were studied. The groups were matched for sex, age, and body mass index. Plasma triglyceride, nonesterified fatty acid (NEFA), glucose, and insulin responses were measured after a mixed meal (35% of daily energy requirements, 50 g of fat) and after a high fat challenge (1362 kcal, 129 g of fat). NEFA concentrations were approximately 15% higher after the mixed meal and peaked earlier and were approximately 20% higher at 7 h in response to the high fat test meal in Thr54 homozygotes compared with Ala54 homozygotes. Insulin responses to the test meals tended to be higher in Thr54 homozygotes, but glucose and triglyceride responses were not different.The results of this study suggest that the Thr54 form of IFABP is associated with higher and prolonged NEFA responses to dietary fat in vivo. Higher NEFA concentrations may contribute to insulin resistance and hyperinsulinemia in individuals with this allele.