Intramuscular Lipid Research Articles

Not only accumulation, but also saturation status of intramuscular lipids is significantly affected by PPARγ activation

Intramuscular lipid accumulation has been associated with insulin resistance, and after thiazolidinediones (TZD) treatment, it was shown to be reduced in some, but not all, studies. This work was undertaken to investigate the relationships between intramuscular lipids [free fatty acids (FFA), diacylglycerols (DAG), triacylglycerol (TAG) and phospholipids] and plasmalemmal expression of fatty acid (FA) transporter [FAT/CD36 and FABPpm] in the muscles of varying oxidative capacity, after peroxisome proliferator-activated receptors gamma (PPARγ) activation (rosiglitazone) in an animal model of high-fat-diet-induced insulin resistance. Endurance training was also included to further explore the differences in these relationships. We have used gas liquid chromatography to estimate FA content and composition in each lipid fraction. For sarcolemmal expression of FA transporters, subfractionation of skeletal muscles with subsequent western blot technique was applied. High-fat diet induced intramuscular accumulation of FFA, DAG and TAG, irrespective of muscle's fibre composition. PPARγ activation (rosiglitazone) and, to a lesser extent, endurance training further increased TAG accumulation, while it reduced DAG in oxidative muscles (soleus and red gastrocnemius). Aforementioned interventions increased also sarcolemmal FAT/CD36 and FABPpm expressions in particular muscles. Irrespective of diet, rosiglitazone and exercise decreased significantly FA saturation status favouring proportionate enhancement in monounsaturated FA (rosiglitazone) or polyunsaturated FAs (endurance training). These findings support the conclusion that not only the change in total lipid content (DAG and TAG), but also FA composition is affected by rosiglitazone in an animal model of high-fat-diet-induced insulin resistance.

PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial insulin sensitivity in obese, insulin-resistant men. In a single-blind, randomized, crossover study, 10 insulin-resistant men consumed 3 high-fat mixed meals (2.6 MJ), which were high in SFAs, MUFAs, or PUFAs. Fasting and postprandial skeletal muscle FA processing was examined by measuring differences in arteriovenous concentrations across the forearm muscle. [²H₂]Palmitate was infused intravenously to label endogenous triacylglycerol and FFAs in the circulation, and [U-¹³C]palmitate was added to the meal to label chylomicron-triacylglycerol. Skeletal muscle biopsy samples were taken to assess intramuscular lipid metabolism and gene expression. Insulin and glucose responses (AUC) after the SFA meal were significantly higher than those after the PUFA meal (P = 0.006 and 0.033, respectively). Uptake of triacylglycerol-derived FAs was lower in the postprandial phase after the PUFA meal than after the other meals (AUC₆₀₋₂₄₀; P = 0.02). The fractional synthetic rate of the triacylglycerol, diacylglycerol, and phospholipid pool was higher after the MUFA meal than after the SFA meal. PUFA induced less transcriptional downregulation of oxidative pathways than did the other meals. PUFAs reduced triacylglycerol-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity, a more transcriptional oxidative phenotype, and altered intramyocellular lipid partitioning and may therefore be protective against the development of insulin resistance.

Lipid metabolism in pigs fed supplemental conjugated linoleic acid and/or dietary arginine

We proposed that the combination of conjugated linoleic acid (CLA) and arginine would decrease adiposity by depressing lipid synthesis in liver and adipose tissues of growing pigs. Pigs were allotted to treatments in a 2 × 2 factorial design with two lipids (CLA or canola oil) and two amino acids [L-arginine or L-alanine (isonitrogenous control)]; supplements were provided from 80 to 110 kg body weight (approximately 4 weeks). Treatment groups (n = 4) were: control (2.05% L-alanine plus 1% canola oil); CLA (2.05% L-alanine plus 1% CLA); arginine (1.0% L-arginine plus 1.0% canola oil); arginine plus CLA (1.0% arginine plus 1.0% CLA). Arginine increased backfat thickness (P = 0.07) in the absence or presence of CLA, and arginine supplementation increased subcutaneous and retroperitoneal adipocyte volume, especially in combination with dietary CLA (interaction P = 0.001). Arginine increased palmitate incorporation into total lipids by over 60% in liver (P = 0.07). Dietary CLA increased palmitate incorporation into lipids in longissimus muscle by over 100% (P = 0.01), and CLA increased longissimus muscle lipid by nearly 20%. CLA increased glucose oxidation to CO(2) by over 80% in retroperitoneal and subcutaneous adipose tissues (P = 0.04), and doubled palmitate oxidation to CO(2) in intestinal duodenal mucosal cells (P = 0.07). Arginine supplementation decreased muscle pH at 45 min postmortem (P = 0.001), indicating elevated early postmortem glycolysis, and CLA and arginine independently increased PGC-1α gene expression in longissimus muscle. CLA but not arginine depressed mTOR gene expression in intestinal duodenal mucosal cells. CLA decreased serum insulin by 50% (P = 0.02) but increased serum triacylglycerols by over 40%. CLA supplementation increased (P ≤ 0.01) total saturated fatty acids in liver and adipose tissue. In conclusion, neither CLA nor arginine depressed tissue lipid synthesis in growing/finishing pigs, and in fact dietary CLA promoted elevated intramuscular lipid and arginine increased carcass adiposity.

Effect of long‐term betaine supplementation on chemical and physical characteristics of three muscles from the Alentejano pig

The use of betaine as a dietary supplement to reduce fat deposition and increase lean muscle mass in pigs is increasing. However, there is no available information on its effect on the physical and chemical (i.e. fatty acid (FA) profile) characteristics of pork. The effects of long-term betaine intake (1 g betaine kg(-1) diet for 20 weeks) on the chemical and physical characteristics of Musculus longissimus dorsi, M. biceps femoris and M. semimembranosus from the Alentejano pig were investigated. The contents of total protein, intramuscular lipids (neutral and polar), myoglobin and total collagen as well as the water-holding capacity, physical colour characteristics and FA profile of the three muscles were determined. With the exception of a significant increase in the intramuscular lipid content of M. longissimus dorsi and M. biceps femoris, betaine supplementation did not influence muscle chemical and colour characteristics or body fat deposition. These data suggest that long-term betaine supplementation selectively increases intramuscular lipid deposition (a trait related to meat quality) while not affecting other chemical (including the atheroprotective FA profile) and physical characteristics of the Alentejano pig muscles studied.

Insulin-sensitizing properties of adiponectin

Adiponectin administration improves glucose tolerance in rodents. This is due to both reductions in hepatic glucose production, and likely improved insulin stimulated glucose disposal in skeletal muscle. Adiponectin's effects in both liver and muscle are believed to be due in large part to AMP-activated protein kinase (AMPK) activation, resulting in a reduction in hepatic gluconeogenic enzymes and increased fatty acid oxidation and reduced ectopic lipid deposition in muscle. In addition, adiponectin can robustly stimulate mitochondrial biogenesis, at least in muscle, and this appears to be due to AMPK-independent mechanisms. Various treatments successful at improving insulin response (thiazolidinediones (TZDs), n-3 polyunsaturated fatty acid (PUFA) supplementation) also stimulate adiponectin production. Obesity and insulin resistance are often characterized by both a state of resistance to adiponectin (both liver and muscle), as well as a reduction in total circulating adiponectin concentrations. The mechanisms underlying the impaired response of muscle and liver to adiponectin have not been clearly elucidated. Surprisingly, the significance of adiponectin resistance, at least in muscle, is not entirely clear. While the development of adiponectin resistance precedes intramuscular lipid accumulation and impaired insulin response in high-fat fed rodents, the restoration of adiponectin response does not appear to be necessary in order to restore insulin response in muscle. Further research examining the cellular mechanisms underlying the development of adiponectin resistance, and the importance of treating this, needs to be conducted.

Effect of production system on physical–chemical, antioxidant and fatty acids composition of Longissimus dorsi and Serratus ventralis muscles from Iberian pig

The effect of three production systems of Iberian pigs namely Montanera (free-range system and feeding based on acorns and grass), Recebo (free-range system and nutrition based in combination of acorns, grass and mixed feeds) and Intensive (confinement with mixed feeds) on some quality traits of Longissimus dorsi (LD) and Serratus ventralis (SV) muscles were studied. Muscles from pigs raised in the Montanera system showed significantly higher CIE L∗, a∗ and b∗ values and higher haem pigment content than those from Intensive system. Similarly, muscles from pigs raised in the Montanera system had significantly higher contents of α and γ-tocopherol and phenolic compounds contents and higher lipophilic and hydrophilic activity antioxidant than those from pigs raised in the Intensive system. Fatty acids profiles from Montanera pigs had significantly higher monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids and lower saturated fatty acids (SFA) than those from pigs raised in the Intensive system. In relation to muscle effect, LD showed lower intramuscular fat (IMF), α-tocopherol, phenolic compounds, lipid oxidation and PUFA, but higher MUFA than SV.

Effect of antioxidant on the fatty acid composition and lipid oxidation of intramuscular lipid in pressurized pork

To investigate the effect of antioxidants on lipid oxidation and fatty acid composition in pressurized pork, minced pork with or without 1% Na2EDTA was pressurized at 500MPa before 7days storage at 4°C. TBARS value, lipid content and fatty acid composition in untreated and high-pressure (HP) treated samples were analyzed. HP treatment induced marked increases in TBARS values and lipolysis of partial phospholipids causing an increase of free fatty acid content. Preferential hydrolysis for polyunsaturated fatty acids (PUFA) in phospholipids resulted in the percentage of PUFA in phospholipids decreasing markedly and thereby that in free fatty acids increasing significantly. Addition of 1% Na2EDTA to minced pork before HP significantly decreased the TBARS values in pressurized samples, but did not inhibit the lipolysis of phospholipids, causing the fatty acid composition of phospholipids and free fatty acids to change similarly to those samples without Na2EDTA.

Effect of dietary polyunsaturated fatty acids on Stearoyl CoA-Desaturase gene expression in intramuscular lipids of lamb

The effect of replacement of dietary sunflower oil (SO) with linseed oil (LO) on Stearoyl CoA desaturase (SCD) gene expression was investigated. Thirty-six lambs were randomly assigned to four groups and fed with one of the experimental diets, consisting of lucerne pellets with oil (60 g/Kg). The diets varied in the percentage of the oil supplemented and were: 100% SO; 66.6% SO plus 33.3% LO; 33.3% SO plus 66.6% LO and 100% LO. The trial period was of 7 weeks. Longissimus dorsi was removed from each carcass and stored at −80°C until the analysis. Total fatty acids composition was determined by gas-chromatograph, while SCD gene expression was assessed by Real-Time Reverse-Transcription PCR. Replacement of SO with LO decreases significantly the SCD mRNA content with a concomitant increment of polyunsatured fatty acids (PUFA) n-3. These results are related to the higher level of PUFA n-3 present in linseed than sunflower. Although, there were differences on mRNA level, there was not a simultaneously changes on SCD activity. In conclusion, PUFA n-3 act on the regulation of mRNA SCD level without affecting the activity of the relative enzyme.

Measurement of precursor enrichment for calculating intramuscular triglyceride fractional synthetic rate

Our goal was to assess the validity of the enrichments of plasma free palmitate and intramuscular (IM) fatty acid metabolites as precursors for calculating the IM triglyceride fractional synthetic rate. We infused U-¹³C₁₆-palmitate in anesthetized rabbits for 3 h and sampled adductor muscle of legs using both freeze-cut and cut-freeze approaches. We found that IM free palmitate enrichment (0.70 ± 0.07%) was lower (P < 0.0001) than IM palmitoyl-CoA enrichment (2.13 ± 0.17%) in samples taken by the freeze-cut approach. The latter was close (P = 0.33) to IM palmitoyl-carnitine enrichment (2.42 ± 0.16%). The same results were obtained from the muscle samples taken by the cut-freeze approach, except the enrichment of palmitoyl-CoA (2.21 ± 0.08%) was lower (P = 0.02) than that of palmitoyl-carnitine (2.77 ± 0.17%). Plasma free palmitate enrichment was ∼2-fold that of IM palmitoyl-CoA enrichment and palmitoyl-carnitine enrichment (P < 0.001). These findings indicate that plasma free palmitate overestimated IM precursor enrichment owing to in vivo IM lipid breakdown, whereas IM free palmitate enrichment underestimated the precursor enrichment because of lipid breakdown during muscle sampling and processing. IM palmitoyl-carnitine enrichment was an acceptable surrogate of the precursor enrichment because it was less affected by in vitro lipid breakdown after sampling.

The curious case of anabolic resistance: old wives' tales or new fables?

the progressive loss of muscle mass, commonly termed sarcopenia, accompanies the process of healthy aging ([27][1]). The underlying basis of this condition, in a very simplistic view, would be at a more advanced age skeletal muscle proteins are being lost because of an imbalance between muscle

Tenderness profiles of ten muscles from F1 Bos indicus x Bos taurus and Bos taurus cattle cooked as steaks and roasts

Twenty Bos taurus (Hereford x Angus crosses) and 20 F1 Bos indicus x Bos taurus heifers of the same age, management and feeding regimen, were harvested and evaluated at 2 days postmortem for carcass and meat traits. Ten muscles were obtained from the right sides and aged until 10 days postmortem. Bos indicus carcasses were lighter, had less fat cover, smaller ribeyes, and less intramuscular lipid (all p ≤ 0.05). Bos taurus longissimus lumborum, gluteus medius, triceps brachii, and semimembranosus muscles cooked as steaks and roasts had a lower Warner–Bratzler shear force (WBSF) ( p ≤ 0.05) than those from Bos indicus. Bos taurus deep pectoral and semitendinosus muscles cooked as roasts had a lower WBSF ( p < 0.05) than Bos indicus. Infraspinatus, longissimus lumborum, and semitendinosus muscles were more tender ( p < 0.05) as roasts than steaks, whereas the opposite was true for the deep pectoral and semimembranosus muscles. Seven of the 10 muscles had lower WBSF ( p ≤ 0.05) for Bos taurus when cooked as steaks, roasts or both.

Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle

During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated eight healthy subjects after a 72-h fast compared with a 10-h overnight fast. Insulin action on skeletal muscle was assessed by a hyperinsulinemic euglycemic clamp and by determining insulin signaling to glucose transport. In addition, substrate oxidation, skeletal muscle lipid content, regulation of glycogen synthesis, and AMPK signaling were assessed. Skeletal muscle insulin sensitivity was reduced profoundly in response to a 72-h fast and substrate oxidation shifted to predominantly lipid oxidation. This was associated with accumulation of both lipid and glycogen in skeletal muscle. Intracellular insulin signaling to glucose transport was impaired by regulation of phosphorylation at specific sites on AS160 but not TBC1D1, both key regulators of glucose uptake. In contrast, fasting did not impact phosphorylation of AMPK or insulin regulation of Akt, both of which are established upstream kinases of AS160. These findings show that insulin resistance in muscles from healthy individuals is associated with suppression of site-specific phosphorylation of AS160, without Akt or AMPK being affected. This impairment of AS160 phosphorylation, in combination with glycogen accumulation and increased intramuscular lipid content, may provide the underlying mechanisms for resistance to insulin in skeletal muscle after a prolonged fast.

NUDT6, the FGF-2’s antisense gene, showed associations with fat deposition related traits in pigs

The nudix (nucleoside diphosphate linked moiety X)-type motif 6 (Nudt6) belongs to the cytosolic Nudix hydrolase family genes, and it has been identified as a fibroblast growth factor 2 (Fgf-2)'s anti-sense gene in humans and rats, and can regulate Fgf-2 stability by its 3' un-translated region (UTR) of mRNA. Here we cloned two completed mRNA of porcine NUDT6 variant transcripts and then analyzed the overlapping relationships of 3'UTR ends between NUDT6 and FGF-2 genes. The expression patterns of NUDT6 were detected in heart, liver, spleen, lung, kidney, muscle and fat tissues, suggesting a widespread mRNA expression of this gene in pigs. The real-time PCR results revealed the reverse expression patterns of NUDT6 and FGF-2 in Tongcheng and Yorkshire pig's tissues including heart, live, spleen, lung, kidney and fat tissues. A C/T single nucleotide polymorphism in NUDT6 was genotyped in two experimental populations, and the association analyses revealed that it was significantly associated with intramuscular fat percentage (P<0.01) and intramuscular lipid (P<0.05) in experiment population 1, and it was significantly associated with percentage of leaf and caul fat (P<0.05), percentage of leaf fat (P<0.05), proportion of lean and bone of the ham (P<0.05) in experimental population 2. The findings from this study could offer new evidences that NUDT6 maybe a candidate gene for fat deposition in pigs.

Effect of high-pressure treatment on the fatty acid composition of intramuscular lipid in pork

To investigate the effect of high-pressure (HP) treatment on lipid oxidation and fatty acid composition of intramuscular lipid in pork, the longissimus muscles from Rongchang (RC) pig were pressurized at 200, 350 and 500MPa for 20min at 20°C prior to 7days storage at 4°C. The changes in TBARS number, lipid content and fatty acid composition of total intramuscular lipids, phospholipids, triglycerides and free fatty acids in untreated and HP treated samples were analyzed. HP treatment had no significant effect on the content and fatty acid composition of total lipids and triglycerides in the samples, but treatment at 350MPa and above led to marked increases in TBARS values and lipolysis of partial phospholipids causing a correlative increase of free fatty acid content. A preferential hydrolysis for polyunsaturated fatty acids (PUFA) in phospholipids was observed, which resulted in the percentage of PUFA in phospholipids decreasing markedly and thereby that in free fatty acids increasing significantly.

Assessment of intra-hepatic and intra-muscular lipid in obese pregnant women: an application of 3-tesla MRI

BackgroundInsulin resistance is exaggerated in both pregnancy and in obesity: obese pregnant women may display earlier onset or exaggerated insulin resistance which could contribute to some of the pregnant pathology...

Regulation of Mitochondrial Biogenesis in Metabolic Syndrome

Insulin resistant individuals manifest multiple disturbances in free fatty acids metabolism and have excessive lipid accumulation in insulin-target tissues. A wide range of evidence suggests that defective muscle mitochondrial metabolism, and subsequent impaired ability to oxidize fatty acids, may be a causative factor in the accumulation of intramuscular lipid and the development of insulin resistance. Such mitochondrial dysfunction includes loss of mitochondria, defects in the mitochondrial OXPHOS system and decreased rate of ATP synthesis. Stimulation of mitochondrial biogenesis appears as a strategy for the clinical management of the metabolic syndrome, by enhancing mitochondrial activity and protecting the cell against the increased flux of reduced substrates to the electron transport chain and thus reducing metabolic inflammation.

Resveratrol attenuates high-fat diet–induced insulin resistance by influencing skeletal muscle lipid transport and subsarcolemmal mitochondrial β-oxidation

Although resveratrol (RES) is implicated in the regulation of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle lipid transportation and lipid oxidation of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)–induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle lipid transportation was studied in rats fed a normal diet, an HFD, and an HFD with intervention of RES for 8 weeks. Citrate synthase (CS), electron transport chain (ETC) activities, and several enzymes for mitochondrial β-oxidation were assessed in SS and IMF mitochondria from tibialis anterior muscle. The HFD-fed rats exhibited obvious systemic and skeletal muscle IR as well as intramuscular lipid accumulation. SIRT1 activity and expression of genes related to mitochondrial biogenesis were greatly declined, whereas the gene for lipid transportation, FAT/CD36, was upregulated ( P < .05). Subsarcolemmal but not IMF mitochondria displayed lower CS, ETC, and β-oxidation activities. By contrast, RES treatment protected rats against diet-induced intramuscular lipid accumulation and IR, increased SIRT1 activity and mitochondrial biogenesis, and reverted the decline in SS mitochondrial CS and ETC activities. Importantly, although expression of FAT/CD36 was increased (11%, P < .05), activities of SS mitochondrial β-oxidation enzymes were largely enhanced (41%∼67%, P < .05). This study suggests that RES ameliorates insulin sensitivity consistent with an improved balance between skeletal muscle lipid transportation and SS mitochondrial β-oxidation in HFD rats.

Intramyocellular lipid droplets increase with progression of cachexia in cancer patients

BackgroundIntramyocellular lipids are an important source of fuel for mitochondrial fat oxidation and play an important role in intramuscular lipid homeostasis. We hypothesised that due to the phenotype associated with cancer cachexia, there would exist an association between increasing weight loss and the number/size of intramyocellular lipid droplets.MethodsNineteen cancer patients and 6 controls undergoing surgery were recruited. A rectus abdominis biopsy was performed and processed for transmission electron microscopy (TEM). The number of intramyocellular lipid droplets and lipid droplet diameter were calculated from the TEM images. CT scans, performed as part of patients' routine care, were analysed to determine amount of adipose (intermuscular, visceral and subcutaneous) and muscle tissue.ResultsCompared with controls, cancer patients had increased numbers of lipid droplets (mean (SD) 1.8 (1.9) vs. 6.4 (9.1) per ×2,650 field, respectively, p = 0.036). Mean (SD) lipid droplet diameter was also higher in cancer patients compared with controls (0.42 (0.13) vs. 0.24 (0.21) μm, p = 0.015). Mean lipid droplet count correlated positively with the severity of weight loss (R = 0.51, p = 0.025) and negatively with CT-derived measures of intermuscular fat (R = −0.53, p = 0.022) and visceral fat (R = −0.51, p = 0.029).ConclusionsThis study suggests that the number and size of intramyocellular lipid droplets is increased in the presence of cancer and increases further with weight loss/loss of adipose mass in other body compartments.

Finishing cattle at pasture at 30 months of age or indoors at 25 months of age: Effects on selected carcass and meat quality characteristics

To examine the effect of a modification of a typically Irish dairy calf-to-beef production system, Charolais×Friesian steers were offered a finishing ration of grass silage ad libitum and 5.6kg concentrates daily for 174days prior to slaughter at 25months of age or grass silage ad libitum for 174days, followed by pasture for 167days and slaughter at 30months of age. Finishing at pasture increased carcass weight (376 vs. 342kg) but did not affect intra-muscular lipid concentration (28 vs. 24g/kg). Finishing at pasture decreased Longissimus thoracis et lumborum lightness (35.6 vs. 36.9) and increased shear force of muscle at 2 (8.54 vs 4.32) and 7days (5.21 vs 3.64kg) post-mortem but not at 14days post-mortem (4.45 vs. 3.42kg). Finishing at pasture did not affect the sensory characteristics of tenderness, juiciness, firmness or chewiness and tended (P<0.1) to decrease texture and acceptability. It is concluded that modification of this beef production system as described, had minor effects on beef quality which are unlikely to be of commercial significance.

The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene

Neutral lipid storage disease is caused by mutations in the CGI-58 or the PNPLA2 genes. Lipid storage can be detected in various cell types including blood granulocytes. While CGI-58 mutations are associated with Chanarin-Dorfman syndrome, a condition characterized by lipid storage and skin involvement (ichthyosis), mutations in the patatin-like phospholipase domain-containing protein 2 gene (PNPLA2) were reported with skeletal and cardiac muscle disease only. We describe clinical, myopathological, magnetic resonance imaging (MRI), and genetic findings of six patients carrying different recessive PNPLA2 mutations. Pulse-chase labeling of control and patient cells with supplementation of clenbuterol, salmeterol, and dexamethasone was performed in vitro. The patients share a recognizable phenotype with prominent shoulder girdle weakness and mild pelvic girdle and distal muscle weakness, with highly elevated creatine kinase (CK) and cardiomyopathy developing at later stages. Muscle histology invariably reveals massive accumulation of lipid droplets. New muscle or whole-body MRI techniques may assist diagnosis and may become a useful tool to quantify intramuscular lipid storage. Four novel and two previously reported mutations were detected, affecting different parts of the PNPLA2 gene. Activation of hormone-sensitive lipase by beta-adrenergic substances such as clenbuterol appears to bypass the enzymatic block in PNPLA2-deficient patient cells in vitro. PNPLA2 deficiency is a slowly progressive myopathy with onset around the third decade. Cardiac involvement is relatively common at a later stage. Muscle MRI may detect increased lipid in a characteristic distribution, which could be used for monitoring disease progression. Beta-adrenergic agents may be beneficial in improving triacylglycerol breakdown in patients with PNPLA2 mutations.