Compared with that of MUFA, a high dietary intake ofn-3 PUFA does not reduce the degree of pathology in mdx mice

Abstract

Duchenne muscular dystrophy (DMD) is a severe muscle disease that affects afflicted males from a young age, and the mdx mouse is an animal model of this disease. Although new drugs are in development, it is also essential to assess potential dietary therapies that could assist in the management of DMD. In the present study, we compared two diets, high-MUFA diet v. high-PUFA diet, in mdx mice. To generate the high-PUFA diet, a portion of dietary MUFA (oleic acid) was replaced with the dietary essential n-3 PUFA a-linolenic acid (ALA). We sought to determine whether ALA, compared with oleic acid, was beneficial in mdx mice. Consumption of the high-PUFA diet resulted in significantly higher n-3 PUFA content and reduced arachidonic acid content in skeletal muscle phospholipids (PL), while the high-MUFA diet led to higher oleate content in PL. Mdx mice on the high-MUFA diet exhibited 2-fold lower serum creatine kinase activity than those on the high-PUFA diet (P,0·05) as well as a lower body fat percentage (P, 0·05), but no significant difference in skeletal muscle histopathology results. There was no significant difference between the dietary groups with regard to phosphorylated p65 (an inflammatory marker) in skeletal muscle.In conclusion, alteration of PL fatty acid (FA) composition by the high-PUFA diet made mdx muscle more susceptible to sarcolemmal leakiness, while the high-MUFA diet exhibited a more favourable impact. These results may be important for designing dietary treatments for DMD patients, and future work on dietary FA profiles, such as comparing other FA classes and dose effects, is needed.Key words: Dystrophic muscle: n-3 Fatty acids: Olive oil: Flaxseed oil Duchenne muscular dystrophy (DMD) is an X-linked, recessive, degenerative muscle disease, and the mdx mouse is an animal model of DMD (1) . Approximately one in 3500 boys are afflicted with the disease (2) . Compared with those in their wild-type counterparts on the same diet, skeletal muscle phospholipid (PL) in mdx mice exhibit increased oleic acid (18 : 1) and linoleic acid (18 : 2) abundances and reduced DHA (22 : 6) abundance (3) . Results from similar assessments of fatty acid (FA) composition in the muscle of human subjects with DMD are unclear due to a lack of dietary control in these studies (4 -6) as well as issues related to age matching and sample handling (5) . In DMD and the mdx mouse, the skeletal muscle sarcolemma is destabilised as a result of a mutation in the dystrophin gene (2) . Corticosteroid treatment is useful but not sufficiently effective (7) , and lifestyle changes could be additionally useful to favourably alter the trajectory of disease progression. Little is known regarding appropriate dietary recommendations for patients with DMD. However, based on known dysfunction in dystrophic muscle, hypotheses can be generated. The skeletal muscle of DMD patients (8,9) and mdx mice (10 -14) exhibits high levels of inflammation and membrane permeability or leakiness. Therefore, dietary treatments that could alter the...

Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy

“…These findings reinforce the idea that endogenously produced fatty-acids are likely functionally distinct from fatty acids imported from circulation or intracellular triglyceride lipolysis [45–47]. We incubated myotubes in OA, EPA, or DHA in addition to PA because of data suggesting that saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids may differentially affect muscle functions in muscular dystrophy [48, 49]. Neither OA, EPA, nor DHA had an effect on SERCA-dependent Ca 2+ uptake.…”

Intensity-dependent and sex-specific alterations in hepatic triglyceride metabolism in mice following acute exercise

“…Plasma glycerol (a marker of whole body lipolysis) and plasma TG concentrations were measured using a commercially available kit (Sigma-Aldrich). For measurement of hepatic TG concentration, lipids were extracted from ϳ8 mg of tissue, and TG content of the extract was determined using a commercially available kit (Sigma-Aldrich) (18,23) and expressed as percentage of liver wet weight.…”

“…Dawn Brasaemle of Rutgers University), MTP (1:100,000; BD Transduction Laboratories, San Jose, CA), cAMP response element-binding protein (CREB) (1:500; Cell Signaling Technology), phospho-CREB Ser133 (1:1,000; Cell Signaling Technology), and ␤-actin (1:2,000; Cell Signaling Technology). Membranes were then incubated with IR Dye 680 (1:10,000; LI-COR Biosciences, Lincoln, NE) or IR Dye 800 (1:10,000; LI-COR Biosciences) secondary antibodies and bands quantified with ␤-actin as a loading control (23).…”

Creatine, L-Carnitine, andω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle

“…Further, initial observations suggest that ω 3 PUFA supplementation with fish oil or EPA decreases muscle degeneration and inflammation in mdx mouse model mirrored by reduced functional impairment evaluated by grip strength tests [207, 208]. On the contrary, by using a highly controlled diet design, Henderson et al [209] have recently put forward a detrimental effect of a high intake of ω 3 PUFA, unlike high MUFA, in the same animal model as demonstrated by higher serum CK activity and no changes in skeletal muscle histopathology and inflammatory markers (p65) [209]. Congruent with the latter observations, Galvao and coworkers [210] have recently demonstrated that high ω 3-PUPA diet enriched with α-linoleic and α-linolenic acid, unlike high long chain saturated fatty acids diet, promotes a negative effect on lifespan in the same animal model with genetic cardiomyopathy.…”