Continuous Supplementation of Milk Fat Globule Membrane with Habitual Exercise from a Young Age Improves Motor Coordination and Skeletal Muscle Function in Aged Mice.

Since the decline of physical performance gradually progresses with aging, continuous exercise with nutritional supplementation from a young age is a feasible and effective way to maintain a comfortable life until late old age. We examined the effects of continuous milk fat globule membrane (MFGM) supplementation combined with voluntary running exercise (VR) for prevention of aging-associated declines in physical performance in naturally aging mice. The MFGM with VR group showed a significantly attenuated age-related decline in motor coordination and suppression of the loss of muscle mass and strength. Compared with the control group, the MFGM with VR group showed significantly higher mRNA and protein expression for docking protein 7, which maintains neuromuscular junction (NMJ) integrity, in the quadriceps muscles. These results suggest that dietary MFGM and VR attenuate natural aging-related decline in motor coordination and muscle function by regulating NMJ integrity.

Emotional State of Being Moved Elicited by Films: A Comparison With Several Positive Emotions.

This study investigated the facial and physiological activities that are associated with the emotional state of being moved. We elicited the emotional states of being moved, amusement, attachment, and calmness by presenting participants with film clips; we assessed their electromyographic, electrodermal, and cardiac responses to the films. Further, we used a high- and low-arousal moving film to examine the effect of different levels of arousal on facial and physiological responses to moving films. We compared facial and physiological responses to positive-emotion and emotionally neutral films. Analysis of subjective emotion scale ratings revealed that the films had successfully elicited the target positive emotions and that the high- and low-arousal moving films had elicited the feeling of being moved in accordance with the anticipated level of intensity. In comparison to the other types of positive-emotion films, the two moving films resulted in an increase in corrugator electromyography activity and skin conductance responses, which in turn were modulated by the arousal level of the moving films. However, cardiac measures such as heart rate did not differ across the different film conditions. These results suggest that film clips can elicit different intensities of the emotional state of being moved and that facial muscle and electrodermal activities but not cardiac activity characterize the film-induced emotional state of being moved.

Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts.

High levels of reactive oxygen species (ROS) contribute to muscle cell death in aging and disuse. We have previously found that resveratrol can reduce oxidative stress in response to aging and hindlimb unloading in rodents in vivo, but it was not known if resveratrol would protect muscle stem cells during repair or regeneration when oxidative stress is high. To test the protective role of resveratrol on muscle stem cells directly, we treated the C2C12 mouse myoblast cell line with moderate (100 µM) or very high (1 mM) levels of H2O2 in the presence or absence of resveratrol. The p21 promoter activity declined in myoblasts in response to high ROS, and this was accompanied a greater nuclear to cytoplasmic translocation of p21 in a dose-dependent matter in myoblasts as compared to myotubes. Apoptosis, as indicated by TdT-mediated dUTP nick-end labeling, was greater in C2C12 myoblasts as compared to myotubes (P<.05) after treatment with H2O2. Caspase-9, -8 and -3 activities were elevated significantly (P<.05) in myoblasts treated with H2O2. Myoblasts were more susceptible to ROS-induced oxidative stress than myotubes. We treated C2C12 myoblasts with 50 µM of resveratrol for periods up to 48 h to determine if myoblasts could be rescued from high-ROS-induced apoptosis by resveratrol. Resveratrol reduced the apoptotic index and significantly reduced the ROS-induced caspase-9, -8 and -3 activity in myoblasts. Furthermore, Bcl-2 and the Bax/Bcl-2 ratio were partially rescued in myoblasts by resveratrol treatment. Similarly, muscle stem cells isolated from mouse skeletal muscles showed reduced Sirt1 protein abundance with H2O2 treatment, but this could be reversed by resveratrol. Reduced apoptotic susceptibility in myoblasts as compared to myotubes to ROS is regulated, at least in part, by enhanced p21 promoter activity and nuclear p21 location in myotubes. Resveratrol confers further protection against ROS by improving Sirt1 levels and increasing antioxidant production, which reduces mitochondrial associated apoptotic signaling, and cell death in myoblasts.

Coffee polyphenols extracted from green coffee beans improve skin properties and microcirculatory function.

Coffee polyphenols (CPPs), including chlorogenic acid, exert various physiological activities. The purpose of this study was to investigate the effects of CPPs on skin properties and microcirculatory function in humans. In this double-blind, placebo-controlled study, 49 female subjects with mildly xerotic skin received either a test beverage containing CPPs (270 mg/100 mL/day) or a placebo beverage for 8 weeks. The ingestion of CPPs significantly lowered the clinical scores for skin dryness, decreased transepidermal water loss, skin surface pH, and increased stratum corneum hydration and the responsiveness of skin blood flow during local warming. Moreover, the amounts of free fatty acids and lactic acid in the stratum corneum significantly increased after the ingestion of CPPs. These results suggest that an 8-week intake of CPPs improve skin permeability barrier function and hydration, with a concomitant improvement in microcirculatory function, leading to efficacy in the alleviation of mildly xerotic skin.

Deletion of nuclear factor-κB p50 upregulates fatty acid utilization and contributes to an anti-obesity and high-endurance phenotype in mice.

The transcription factor nuclear factor-κB (NF-κB) plays an important role in regulating physiological processes such as immunity and inflammation. In addition to this primary role, NF-κB interacts physically with peroxisome proliferator-activated receptors regulating lipid metabolism-related gene expression and inhibits their transcriptional activity. Therefore, inhibition of NF-κB may promote fatty acid utilization, which could ameliorate obesity and improve endurance capacity. To test this hypothesis, we attempted to elucidate the energy metabolic status of mice lacking the p50 subunit of NF-κB (p50 KO mice) from the tissue to whole body level. p50 KO mice showed a significantly lower respiratory quotient throughout the day than did wild-type (WT) mice; this decrease was associated with increased fatty acid oxidation activity in liver and gastrocnemius muscle of p50 KO mice. p50 KO mice that were fed a high-fat diet were also resistant to fat accumulation and adipose tissue inflammation. Furthermore, p50 KO mice showed a significantly longer maximum running time compared with WT mice, with a lower respiratory exchange ratio during exercise as well as higher residual muscle glycogen content and lower blood lactate levels after exercise. These results suggest that p50 deletion facilitates fatty acid catabolism, leading to an anti-obesity and high-endurance phenotype of mice and supporting the idea that NF-κB is an important regulator of energy metabolism.

Habitual exercise plus dietary supplementation with milk fat globule membrane improves muscle function deficits via neuromuscular development in senescence-accelerated mice.

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.

Dietary milk fat globule membrane improves endurance capacity in mice.

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.

Catechins suppress muscle inflammation and hasten performance recovery after exercise.

INTRODUCTION: Catechins, abundant in green tea, exhibit many biological actions for potential clinical applications. Our purpose was to explore the potential benefits of catechin ingestion on recovery of physical performance after downhill running. METHODS: Institute of Cancer Research mice were used to examine the effects of prior catechin ingestion (0.5% w/w in diet for 3 wk) on 1) wheel-running activity, 2) running endurance, 3) muscle force, and 4) muscle oxidative stress and inflammation after downhill running (16 m·min for 5 min, 18 m·min for 5 min, 20 m·min for 10 min, and 22 m·min for 130 min). RESULTS: Voluntary wheel-running activity and the contractile force of the isolated soleus muscle decreased (P < 0.05) after downhill running. Notably, catechin ingestion significantly alleviated the running-induced decrease in voluntary wheel-running activity by 35%; the catechin-treated mice maintained endurance running capacity (214 ± 9 vs 189 ± 10 min, P < 0.05). Furthermore, catechins alleviated (P < 0.05) the decrease in tetanic force evident in the soleus muscle after downhill running. Catechins suppressed the running-induced increases in plasma creatine phosphokinase levels by 52%; this was also true of the carbonylated protein content of the soleus muscle by 17% (P < 0.05), malondialdehyde levels by 32% in the gastrocnemius muscle, and myeloperoxidase activity of the gastrocnemius by 22% (P < 0.05). The levels of tumor necrosis factor-α, interleukin-1ß, and monocyte chemoattractant protein-1 in the gastrocnemius muscle were significantly lower (P < 0.05) by 33%, 29%, and 35%, respectively, in treated mice; the expression levels of mRNAs encoding these fell in parallel. CONCLUSION: Our results suggest that long-term intake of catechins, perhaps through their antioxidant properties, attenuates downhill running-induced muscle damage by suppressing muscle oxidative stress and inflammation, hastening recovery of physical performance in mice.

Hydroxypropylated distarch phosphate versus unmodified tapioca starch: fat oxidation and endurance in C57BL/6J mice.

An RS4-type resistant starch is a chemically modified starch that shows reduced availability in comparison to the corresponding unmodified starch. Hydroxypropylated distarch phosphate (HDP) is an RS4-type resistant starch that increases energy expenditure and prevents high-fat diet-induced obesity through increased hepatic fatty acid oxidation. The aim of this study was to clarify the acute effects of HDP from tapioca starch (HPdTSP) on physical performance in mice. Male C57BL/6J mice were used to examine the effects of a single administration of 2 mg/g body weight HPdTSP or unmodified tapioca starch (TS) on postprandial responses in serum metabolic parameters, running endurance capacity on a treadmill, whole-body energy metabolism during exercise, activity of enzymes involved in fatty acid oxidation, liver and gastrocnemius muscle glycogen content, and serum glucose, insulin, non-esterified fatty acid, lactate, and triglyceride levels after exercise. Running time to fatigue was significantly greater in HPdTSP mice than in TS mice. Furthermore, HPdTSP maintained higher fat oxidation and this was associated with a greater activity of enzymes in fatty acid oxidation in the muscle during exercise. The blood lactate and serum insulin levels after exercise was significantly lower in HPdTSP mice than in TS mice. Liver glycogen was significantly higher in HPdTSP mice than in TS mice. These results suggest that acute oral administration of the RS4-type resistant starch, HPdTSP, maintained higher fat oxidation and reduced liver glycogen consumption during exercise and increased running endurance capacity in mice.

Capsiate, a non-pungent capsaicin analog, reduces body fat without weight rebound like swimming exercise in mice.

Enhancement of energy expenditure and reducing energy intake are crucial for weight control. Capsiate, a non-pungent capsaicin analog, is known to suppress body fat accumulation and reduce body weight by enhancing of energy expenditure in both mice and humans. However, it is poorly understood whether suppressing body fat accumulation by capsiate administration is equal to exercise or not. The aim of this study is to compare the effects of repeated administration of capsiate and exercise and to investigate the weight rebound after repeated capsiate administration and/or exercise. In the present study, we report that 2 weeks treatment of capsiate and exercise increased energy metabolism and suppressed body fat accumulation during 4 more weeks of ad libitum feeding. The body weight in capsiate and exercise groups was significantly lower than that of control group. The oxygen consumption was significanlty increased in capsiate and exercise groups than in the vehicle administered mice. In addition, the abdominal adipose tissue weight in capsiate and exercise groups was significantly lower than that of control group. These results indicate that suppressing body fat accumulation by capsiate intake is beneficial for maintaining an ideal body weight as exercise.

Catechins attenuate eccentric exercise-induced inflammation and loss of force production in muscle in senescence-accelerated mice.

Catechins have a great variety of biological actions. We evaluated the potential benefits of catechin ingestion on muscle contractile properties, oxidative stress, and inflammation following downhill running, which is a typical eccentric exercise, in senescence-accelerated prone mice (SAMP). Downhill running (13 m/min for 60 min; 16° decline) induced a greater decrease in the contractile force of soleus muscle and in Ca(2+)-ATPase activity in SAMP1 compared with the senescence-resistant mice (SAMR1). Moreover, compared with SAMR1, SAMP1 showed greater downhill running-induced increases in plasma CPK and LDH activity, malondialdehyde, and carbonylated protein as markers of oxidative stress; and in protein and mRNA expression levels of the inflammatory mediators such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in muscle. SAMP1 exhibited aging-associated vulnerability to oxidative stress and inflammation in muscle induced by downhill running. Long-term (8 wk) catechin ingestion significantly attenuated the downhill running-induced decrease in muscle force and the increased inflammatory mediators in both plasma and gastrocnemius muscle. Furthermore, catechins significantly inhibited the increase in oxidative stress markers immediately after downhill running, accompanied by an increase in glutathione reductase activity. These findings suggest that long-term catechin ingestion attenuates the aging-associated loss of force production, oxidative stress, and inflammation in muscle after exercise.

Tea catechins prevent contractile dysfunction in unloaded murine soleus muscle: a pilot study.

OBJECTIVE: Extended periods of muscle disuse, physical inactivity, immobilization, and bedrest result in a loss of muscle mass and a decrease in muscle force, which are accompanied by an increase in oxidative stress. We investigated the effects of the intake of green tea catechins on unloading-induced muscle dysfunction in tail-suspended mice. METHODS: Ten-week-old male BALB/c mice were fed a purified control diet or a diet containing 0.5% tea catechins for 14 d. Thereafter, the mice were subjected to continuous tail suspension for 10 d. On the final day, muscle mass, contractile force production, antioxidant potential, and carbonylated protein levels were evaluated. RESULTS: Hind limb unloading caused a loss of soleus muscle weight and muscle force. Intake of tea catechins significantly inhibited the unloading-induced decrease in force in isolated soleus muscle by 19% compared with the control group, although tea catechins did not affect muscle weight. In addition, intake of tea catechins suppressed the decrease in antioxidant potential and the increase in carbonyl myofibrillar protein. CONCLUSION: Ingestion of tea catechins minimized contractile dysfunction in skeletal muscle and muscle atrophy in unloaded muscle. This effect might be partly due to the lower oxidative modification of myofibrillar protein through the antioxidant activity of tea catechins.

Aging-associated changes in physical performance and energy metabolism in the senescence-accelerated mouse.

The aim of the study was to clarify the aging-associated changes in physical performance and energy metabolism in senescence-accelerated prone mouse (SAMP1). The endurance of aged SAMP1 was significantly lower by 28% than the age-matched senescence-resistant mouse (SAMR1). Oxygen consumption and fat oxidation in aged SAMP1 were lower by 19% and 22%, respectively. Peroxisome proliferator-activated receptor-γ coactivator-1ß and medium-chain acyl coenzyme A dehydrogenase messenger RNA expression was significantly lower in aged SAMP1. Aged SAMP1 exhibited higher plasma glucose, insulin, leptin, and lower adiponectin concentrations. Aged SAMP1 also had higher malondialdehyde levels in plasma and tissues and lower peroxisome proliferator-activated receptor-γ messenger RNA and protein levels in adipose tissue. These results indicate that physical performance and energy expenditure decrease earlier with aging in SAMP1, accompanied by decreased fatty acid catabolism in muscle and liver and increased inflammation and oxidative stress in adipose tissue. SAMP1 could thus be a useful accelerated functional depression model for studying physical performance and energy metabolism.

Red grape leaf extract improves endurance capacity by facilitating fatty acid utilization in skeletal muscle in mice.

Improving endurance capacity leads to increased athletic performance and active lifestyles. The aim of this study was to investigate the effect of the intake of red grape leaf extract (RGLE), used as a traditional herbal medicine in the Mediterranean area, on endurance capacity in mice. Male BALB/c mice were divided into three experimental groups with similar swimming times and body weights; control group, 0.2% (w/w) and 0.5% RGLE group. Swimming times were measured for evaluation of endurance capacity once a week during the 10-week experimental period. Blood and tissues were collected from anesthetized mice immediately after 30 min of swimming exercise, and analyzed blood component and fatty acid oxidation enzyme activity, and gene expression in soleus muscle and mesenteric adipose tissue. Endurance capacity was improved by RGLE in a dose-related manner, and was significantly longer in the 0.5% RGLE group than in the control group at week 10. Plasma lactate levels after exercise in the 0.5% RGLE group were significantly lower than that in the control group. RGLE induced the upregulation of hormone-sensitive lipase mRNA in mesenteric adipose tissue, increased the plasma free fatty acid concentration after exercise, and enhanced fatty acid oxidation enzyme activity in the soleus muscle. Furthermore, peroxisome proliferator-activated receptor-gamma coactivator 1α (Pgc1α) and its downstream target genes were also significantly upregulated in the soleus muscle in the 0.5% RGLE group. Intake of RGLE upregulated Pgc1α expression and facilitated fatty acid oxidation in skeletal muscle, and these effects contributed, in part, to improve endurance capacity.

Capsinoids, non-pungent capsaicin analogs, reduce body fat accumulation without weight rebound unlike dietary restriction in mice.

Enhancing energy expenditure and reducing energy intake are both crucial for weight control. Capsinoids, which are non-pungent capsaicin analogs, are known to suppress body fat accumulation and reduce body weight by enhancing energy expenditure in both mice and humans. However, it is poorly understood whether the suppression of body fat accumulation by capsinoids has an advantage over dietary restriction. This study shows that the oxygen consumption was increased in mice administered with capsinoids but not in dietary-restricted mice, although there was a similar suppression of body fat accumulation in both groups. The weight rebound was more notable in the dietary-restricted mice than in the mice administered with capsinoids. These results indicate that suppressing body fat accumulation by capsinoids was more beneficial than a restricted diet for maintaining body weight.

Nootkatone, a characteristic constituent of grapefruit, stimulates energy metabolism and prevents diet-induced obesity by activating AMPK.

AMP-activated protein kinase (AMPK) is a serine/threonine kinase that is implicated in the control of energy metabolism and is considered to be a molecular target for the suppression of obesity and the treatment of metabolic syndrome. Here, we identified and characterized nootkatone, a constituent of grapefruit, as a naturally occurring AMPK activator. Nootkatone induced an increase in AMPKalpha1 and -alpha2 activity along with an increase in the AMP/ATP ratio and an increase the phosphorylation of AMPKalpha and the downstream target acetyl-CoA carboxylase (ACC), in C(2)C(12) cells. Nootkatone-induced activation of AMPK was possibly mediated both by LKB1 and Ca(2+)/calmodulin-dependent protein kinase kinase. Nootkatone also upregulated PPARgamma coactivator-1alpha in C(2)C(12) cells and C57BL/6J mouse muscle. In addition, administration of nootkatone (200 mg/kg body wt) significantly enhanced AMPK activity, accompanied by LKB1, AMPK, and ACC phosphorylation in the liver and muscle of mice. Whole body energy expenditure evaluated by indirect calorimetry was also increased by nootkatone administration. Long-term intake of diets containing 0.1% to 0.3% (wt/wt) nootkatone significantly reduced high-fat and high-sucrose diet-induced body weight gain, abdominal fat accumulation, and the development of hyperglycemia, hyperinsulinemia, and hyperleptinemia in C57BL/6J mice. Furthermore, endurance capacity, evaluated as swimming time to exhaustion in BALB/c mice, was 21% longer in mice fed 0.2% nootkatone than in control mice. These findings indicate that long-term intake of nootkatone is beneficial toward preventing obesity and improving physical performance and that these effects are due, at least in part, to enhanced energy metabolism through AMPK activation in skeletal muscle and liver.

Phospho-ablated Id2 is growth suppressive and pro-apoptotic in proliferating myoblasts.

Inhibitor of differentiation protein-2 (Id2) is a dominant negative helix-loop-helix (HLH) protein, and a positive regulator of proliferation, in various cells. The N-terminal region of Id2 contains a consensus cdk2 phosphorylation sequence SPVR, which may be involved with the induction of apoptosis, at least in myeloid 32d.3 cells. However, the role of Id2 phosphorylation at serine 5 in skeletal muscle cells is unknown. The objective of this study was to determine if the phosphorylation of Id2 at serine 5 alters its cellular localization and its role in apoptosis in C2C12 myoblasts. Overexpression of wild type Id2 decreased MyoD protein expression, which corresponded to the increased binding of Id2 to basic HLH proteins E47 and E12. Bromodeoxyuridine incorporation was significantly decreased by the overexpression of phospho-ablated Id2 (S5A); conversely, overexpression of wild type Id2 increased cellular proliferation. The subcellular localization of Id2 and phospho-mimicking Id2 (S5D) were predominantly nuclear compared to S5A. The decreased nuclear localization of S5A corresponded to a decrease in cellular proliferation, and an increase in apoptosis. These data suggest that unphosphorylated Id2 is primarily localized in the cytosol, where it is growth suppressive and potentially pro-apoptotic. These results imply that reducing unphosphorylated Id2 may improve the pool of myoblasts available for differentiation by increasing proliferation and inhibiting apoptosis.

Catechin-induced activation of the LKB1/AMP-activated protein kinase pathway.

Catechins are abundant in green tea and induce a variety of biologic actions, including anti-cancer, anti-obesity, and anti-diabetes effects, and their clinical application has been widely investigated. To clarify the underlying molecular mechanisms of these actions, we examined the effect of catechins on AMP-activated protein kinase (AMPK) in cultured cells and in mice. In Hepa 1-6, L6, and 3T3-L1 cells, epigallocatechin gallate (EGCG) induced increases in AMPKalpha and the downstream target acetyl-CoA carboxylase (ACC) phosphorylation, and AMPKalpha activity. Analysis of the molecular specificity of eight naturally occurring catechins revealed that catechins with a gallocatechin moiety or a galloyl residue act as AMPK activators. In addition, phosphorylation of LKB1, which is a tumor-suppressor protein and a major AMPK-kinase, was increased by catechin treatment. EGCG-induced phosphorylation of LKB1 and AMPKalpha was suppressed by treatment with catalase, suggesting that reactive oxygen species are involved in EGCG-induced activation of the LKB1/AMPK pathway. Oral administration of EGCG (200mg/kg body weight) to BALB/c mice induced an increase in AMPKalpha activity in the liver concomitant with a significant increase in AMPKalpha and ACC phosphorylation. EGCG administration also increased oxygen consumption and fat oxidation, as determined by indirect calorimetry. These findings suggest that multiple effects of catechins, including anti-obesity and anti-cancer effects, are mediated, at least in part, by the activation of LKB1/AMPK in various tissues, and that these effects vary according to the catechin structure.

Different contribution of muscle and liver lipid metabolism to endurance capacity and obesity susceptibility of mice.

We investigated strain differences in whole body energy metabolism, peripheral lipid metabolism, and energy metabolism-related gene expression and protein levels in BALB/c, C57BL/6J, and A/J mice to evaluate the relationship between endurance capacity, susceptibility to diet-induced obesity, and differences in lipid metabolism in muscle and liver. A high-fat diet significantly increased body weight and fat weight in C57BL/6J mice, but not in BALB/c and A/J mice. The endurance capacity of BALB/c mice was 52% greater than that of C57BL/6J mice and 217% greater than that of A/J mice. The respiratory exchange ratio was lowest in BALB/c mice, higher in C57BL/6J mice, and highest in A/J mice, which inversely correlated with the endurance capacity and fatty acid beta-oxidation activity in the muscle. Plasma lactate levels measured immediately after exercise were lowest in BALB/c mice and highest in A/J mice, although there was no difference under resting conditions, suggesting that carbohydrate breakdown is suppressed by enhanced fat utilization during exercise in BALB/c mice. On the other hand, the body weight increase induced by high-fat feeding was related to a reduced whole body energy expenditure, higher respiratory quotient, and lower fatty acid beta-oxidation activity in the liver. In addition, beta-oxidation activity in the muscle and liver roughly paralleled the mRNA and protein levels of lipid metabolism-related molecules, such as peroxisome proliferator-activated receptor and medium-chain acyl-CoA dehydrogenase, in each tissue. These findings indicate that genetically determined basal muscle and liver lipid metabolism and responsiveness to exercise influence physical performance and obesity susceptibility.