We examined the effects of habitual exercise plus nutritional intervention through consumption of milk fat globule membrane (MFGM), a milk component, on aging-related deficits in muscle mass and function in senescence-accelerated P1 mice. Combining wheel-running and MFGM (MFGMEx) intake significantly attenuated age-related declines in quadriceps muscle mass (control: 318 ± 6 mg; MFGMEx: 356 ± 9 mg; P < 0.05) and in contractile force (1.4-fold and 1.5-fold higher in the soleus and extensor digitorum longus muscles, respectively). Microarray analysis of genes in the quadriceps muscle revealed that MFGMEx stimulated neuromuscular development; this was supported by significantly increased docking protein-7 (Dok-7) and myogenin mRNA expression. Treatment of differentiating myoblasts with MFGM-derived phospholipid or sphingolipid fractions plus mechanical stretching also significantly increased Dok-7 mRNA expression. These findings suggest that habitual exercise plus dietary MFGM improves muscle function deficits through neuromuscular development, and that phospholipid and sphingolipid in MFGM contribute to its physiological actions.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-339) contains supplementary material, which is available to authorized users.
The hydrosulfido-bridged diruthenium complex
[Cp*RuCl(μ-SH)2RuCp*Cl] (4; Cp* =
η5-C5Me5) was obtained by the reaction of
either [(Cp*Ru)4(μ3-Cl)4]
(1) or [Cp*RuCl(μ-Cl)2RuCp*Cl] with excess H2S gas, while the reactions of
1 with thiols resulted in the formation
of the thiolato-bridged diruthenium complexes
[Cp*RuCl(μ-SR)2RuCp*Cl] (R = Et (5a),
C6H4Me-p). When a solution of 4 in toluene was
heated at reflux, the cubane-type tetraruthenium
sulfido cluster
[(Cp*Ru)4(μ3-S)4]Cl2
(6) was produced. On the other hand, treatment of
4
with 2 molar equiv of [RhCl(PPh3)3] in
THF at room temperature afforded the triangular
heterometallic sulfido cluster
[(Cp*Ru)2(μ2-H)(μ3-S)2RhCl2(PPh3)]
(10). X-ray analyses have
been undertaken to determine the detailed structures for 4,
5a, 6, and 10.
The hydrosulfido-bridged diruthenium complex [Cp*RuCl(μ2-SH)2RuClCp*] (1) reacted with
an excess of triethylamine to give the cubane-type tetraruthenium sulfido cluster [(Cp*Ru)4(μ3-S)4] (3). When the reaction was carried out in the presence of alkynes, the dithiolene-bridged diruthenium complexes [(Cp*Ru)2(μ2-η2:η4-S2C2RR‘)] (4) were obtained. The dithiolene ring in 4 is almost planar. Treatment of 4 with CO afforded the carbonyl complexes
[Cp*Ru(CO)(μ2-η2:η4-S2C2RR‘)RuCp*] (5) containing a bent dithiolene ring. On the other
hand, the reaction of 1 with an equimolar amount of [RuH2(PPh3)4] resulted in the formation
of the triruthenium sulfido cluster [(Cp*Ru)2(μ3-S)2(μ2-H)RuCl(PPh3)2] (6). Cluster 6 reacted
with an excess of NaBH4 in ethanol to give the dihydrido cluster [(Cp*Ru)2(μ3-S)2(μ2-H)RuH(PPh3)2] (7), which was further converted to the dicarbonyl cluster [(Cp*Ru)2(μ3-S)2Ru(CO)2(PPh3)] (8) under CO. The detailed structures for [(Cp*Ru)2(μ2-η2:η4-S2C2HBut)] (4a),
[Cp*Ru(CO)(μ2-η2:η4-S2C2HBut)RuCp*] (5a), and 6−8 have been determined by X-ray
crystallography.
Milk fat globule membrane (MFGM) comprises carbohydrates, membrane-specific proteins, glycoproteins, phospholipids, and sphingolipids. We evaluated the effects of MFGM consumption over a 12-wk period on endurance capacity and energy metabolism in BALB/c mice. Long-term MFGM intake combined with regular exercise improved endurance capacity, as evidenced by swimming time until fatigue, in a dose-dependent manner. The effect of dietary MFGM plus exercise was accompanied by higher oxygen consumption and lower respiratory quotient, as determined by indirect calorimetry. MFGM intake combined with exercise increased plasma levels of free fatty acids after swimming. After chronic intake of MFGM combined with exercise, the triglyceride content in the gastrocnemius muscle increased significantly. Mice given MFGM combined with exercise had higher mRNA levels of peroxisome proliferator-activated receptor-γ coactivator 1α (Pgc1α) and CPT-1b in the soleus muscle at rest, suggesting that increased lipid metabolism in skeletal muscle contributes, in part, to improved endurance capacity. MFGM treatment with cyclic equibiaxial stretch consisting of 10% elongation at 0.5 Hz with 1 h on and 5 h off increased the Pgc1α mRNA expression of differentiating C2C12 myoblasts in a dose-dependent manner. Supplementation with sphingomyelin increased endurance capacity in mice and Pgc1α mRNA expression in the soleus muscle in vivo and in differentiating myoblasts in vitro. These results indicate that dietary MFGM combined with exercise improves endurance performance via increased lipid metabolism and that sphingomyelin may be one of the components responsible for the beneficial effects of dietary MFGM.
Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], β-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms.
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