\u672c\u7814\u7a76\u306f\u3001\u9ad8\u8102\u80aa\u98df\u80a5\u6e80\u30de\u30a6\u30b9\u306e\u9aa8\u683c\u7b4b\u7531\u6765\u7d30\u80de\u5916\u5c0f\u80de\uff08EV\uff09\u203b1\u306e\u30de\u30a4\u30af\u30edRNA\uff08miRNA\uff09\u203b\u306b\u5bfe\u3059\u308b\u6982\u65e5\u30ea\u30ba\u30e0\u203b3\u3068\u904b\u52d5\u306e\u5f71\u97ff\u3092\u691c\u8a0e\u3057\u3001\u904b\u52d5\u3088\u308a\u3082\u6982\u65e5\u4f4d\u76f8\u306e\u65b9\u304c\u5f37\u304f\u5bc4\u4e0e\u3059\u308b\u3053\u3068\u3092\u660e\u3089\u304b\u306b\u3057\u307e\u3057\u305f\u3002<\/p>\n
This study examined how circadian phase and exercise affect the microRNA (miRNA) composition of skeletal muscle-derived extracellular vesicles (EVs) in high-fat-diet obese mice, demonstrating that circadian phase contributed more to EVs\u2019 miRNA variance than exercise itself.<\/p>\n
\u9aa8\u683c\u7b4b\u306f\u3001\u69d8\u3005\u306a\u751f\u7406\u6d3b\u6027\u7269\u8cea\u3084\u7d30\u80de\u5916\u5c0f\u80de\uff08EV\uff09\u306e\u5206\u6ccc\u3092\u901a\u3058\u3066\u3001\u4ed6\u306e\u81d3\u5668\u3068\u60c5\u5831\u4f1d\u9054\u3092\u884c\u3063\u3066\u3044\u307e\u3059\u3002\u904b\u52d5\u306fEV\u306emiRNA\u7d44\u6210\u3092\u5909\u5316\u3055\u305b\u308b\u3053\u3068\u304c\u77e5\u3089\u308c\u3066\u3044\u307e\u3059\u304c\u3001\u305d\u306e\u591a\u304f\u306f\u6025\u6027\u904b\u52d5\u306e\u5f71\u97ff\u306b\u7740\u76ee\u3057\u305f\u3082\u306e\u3067\u3042\u308a\u3001\u9577\u671f\u7684\u306a\u30c8\u30ec\u30fc\u30cb\u30f3\u30b0\u3084\u3001\u7279\u306b\u300c\u3044\u3064\u904b\u52d5\u3059\u308b\u304b\u300d\u3068\u3044\u3046\u6642\u9593\u5e2f\uff08\u6982\u65e5\u30ea\u30ba\u30e0\uff09\u304cEV miRNA\u306e\u6162\u6027\u7684\u306a\u9069\u5fdc\u306b\u53ca\u307c\u3059\u5f71\u97ff\u306b\u3064\u3044\u3066\u306f\u3001\u3053\u308c\u307e\u3067\u307b\u3068\u3093\u3069\u5206\u304b\u3063\u3066\u3044\u307e\u305b\u3093\u3067\u3057\u305f\u3002\u307e\u305f\u3001\u6982\u65e5\u6642\u8a08\u306f\u9aa8\u683c\u7b4b\u4ee3\u8b1d\u3092\u542b\u3080\u591a\u304f\u306e\u751f\u7406\u6a5f\u80fd\u3092\u5236\u5fa1\u3057\u3066\u3044\u307e\u3059\u304c\u3001EV\u306e\u5206\u6ccc\u3084miRNA\u7d44\u6210\u306b\u304a\u3051\u308b\u6982\u65e5\u30ea\u30ba\u30e0\u306e\u5f79\u5272\u306f\u5341\u5206\u306b\u89e3\u660e\u3055\u308c\u3066\u3044\u307e\u305b\u3093\u3067\u3057\u305f\u3002<\/p>\n
Skeletal muscle communicates with other organs by secreting various bioactive substances and extracellular vesicles (EVs). While exercise is known to alter the miRNA composition of EVs, most prior work has focused on the effects of acute exercise, and little was known about how long-term training\u2014and particularly the time of day at which exercise is performed\u2014chronically shapes the EV miRNA profile. Although the circadian clock regulates many physiological processes including skeletal muscle metabolism, its role in EV secretion and miRNA cargo composition remained poorly understood.<\/p>\n
\u672c\u7814\u7a76\u3067\u306f\u3001\u4f11\u606f\u671f\uff08ZT3\uff09\u3068\u6d3b\u52d5\u671f\uff08ZT15\uff09\u3001\u5ea7\u4f4d\u3068\u904b\u52d5\u3068\u3044\u30462\u00d72\u8981\u56e0\u30c7\u30b6\u30a4\u30f3\u3092\u7528\u3044\u3001\u9ad8\u8102\u80aa\u98df\u3067\u80a5\u80b2\u3057\u305f\u30de\u30a6\u30b9\u306e\u5927\u817f\u56db\u982d\u7b4b\u7531\u6765EV\u306emiRNA\u30d7\u30ed\u30d5\u30a1\u30a4\u30eb\u3092\u7db2\u7f85\u7684\u306b\u89e3\u6790\u3057\u307e\u3057\u305f\u3002\u4e3b\u6210\u5206\u5206\u6790\uff08PCA\uff09\u203b4\u306b\u3088\u308a\u3001\u6982\u65e5\u4f4d\u76f8\u304cEV miRNA\u767a\u73fe\u306e\u5168\u4f53\u7684\u306a\u3070\u3089\u3064\u304d\u306e\u6700\u5927\u306e\u8981\u56e0\u3067\u3042\u308b\u3053\u3068\u304c\u5224\u660e\u3057\u307e\u3057\u305f\uff08\u7b2c1\u4e3b\u6210\u5206\u306e33.47%\uff09\u3002\u5ea7\u4f4d\u6761\u4ef6\u4e0b\u3067\u306f\u3001\u7b4b\u5206\u5316\u306b\u95a2\u308f\u308bmiR-1\u30d5\u30a1\u30df\u30ea\u30fc\u203b5\u304a\u3088\u3073\u30a4\u30f3\u30b9\u30ea\u30f3\u62b5\u6297\u6027\u306b\u95a2\u9023\u3059\u308bmiR-29\u30d5\u30a1\u30df\u30ea\u30fc\u304c\u6d3b\u52d5\u671f\uff08ZT15\uff09\u3067\u6709\u610f\u306b\u4e0a\u6607\u3057\u307e\u3057\u305f\u304c\u3001\u3053\u306e\u5909\u5316\u306f\u904b\u52d5\u6761\u4ef6\u4e0b\u3067\u306f\u8a8d\u3081\u3089\u308c\u307e\u305b\u3093\u3067\u3057\u305f\u3002\u3055\u3089\u306b\u3001\u904b\u52d5\u306b\u3088\u308bmiRNA\u5909\u5316\u306f\u4f4d\u76f8\u4f9d\u5b58\u7684\u3067\u3042\u308b\u3053\u3068\u3082\u660e\u3089\u304b\u306b\u306a\u308a\u307e\u3057\u305f\u3002<\/p>\n
Using a 2\u00d72 factorial design (rest phase ZT3 vs. active phase ZT15; sedentary vs. exercise), we comprehensively profiled the miRNA cargo of quadriceps muscle-derived EVs in high-fat-diet obese mice. Principal component analysis showed that circadian phase was the largest contributor to overall variance in EV miRNA expression (33.47% of PC1). Under sedentary conditions, the myogenesis-related miR-1 family and the insulin-resistance-related miR-29 family were significantly elevated during the active phase (ZT15), but this pattern was not observed under exercise conditions. Exercise-induced miRNA changes were also found to be phase-dependent.<\/p>\n
\u5927\u817f\u56db\u982d\u7b4b\u306e\u6458\u51fa\u7d44\u7e54\u3092\u7121\u8840\u6e05\u57f9\u5730\u3067\u57f9\u990a\u3057\u3001\u305d\u306e\u57f9\u990a\u4e0a\u6e05\u304b\u3089EV\u3092\u56de\u53ce\u3059\u308bex vivo\u57f9\u990a\u6cd5\u3092\u7528\u3044\u307e\u3057\u305f\u3002\u56de\u53ce\u3057\u305fEV\u304b\u3089\u5c0f\u5206\u5b50RNA\u3092\u62bd\u51fa\u3057\u3001\u6b21\u4e16\u4ee3\u30b7\u30fc\u30b1\u30f3\u30b5\u30fc\u306b\u3088\u308b\u7db2\u7f85\u7684miRNA\u30d7\u30ed\u30d5\u30a1\u30a4\u30ea\u30f3\u30b0\u3092\u5b9f\u65bd\u3057\u307e\u3057\u305f\u3002\u7d71\u8a08\u89e3\u6790\u3067\u306f\u3001\u8907\u5408\u52b9\u679c\uff08\u6982\u65e5\u4f4d\u76f8\u5168\u4f53\u30fb\u904b\u52d5\u5168\u4f53\uff09\u3068\u6761\u4ef6\u5225\u306e\u6bd4\u8f03\u3092\u7d44\u307f\u5408\u308f\u305b\u305f\u89e3\u6790\u30c7\u30b6\u30a4\u30f3\u3092\u63a1\u7528\u3057\u3001\u3055\u3089\u306b\u5b9f\u9a13\u7684\u306b\u691c\u8a3c\u3055\u308c\u305fmiRNA\u6a19\u7684\u907a\u4f1d\u5b50\u30c7\u30fc\u30bf\u30d9\u30fc\u30b9\uff08miRTarBase\uff09\u3092\u7528\u3044\u305f\u6a19\u7684\u907a\u4f1d\u5b50\u306e\u6a5f\u80fd\u89e3\u6790\uff08GO\u30fbKEGG\u89e3\u6790\u203b6\uff09\u3092\u884c\u3044\u307e\u3057\u305f\u3002<\/p>\n
We employed an ex vivo culture method in which excised quadriceps muscle tissue was cultured in serum-free medium and EVs were recovered from the conditioned medium. Small RNA was extracted from the isolated EVs and comprehensively profiled using next-generation sequencing. Differential expression was assessed using both composite (overall phase\/exercise) and condition-specific comparisons, and functional enrichment analysis (GO and KEGG) of experimentally validated target genes was performed using the miRTarBase database.<\/p>\n
\u672c\u7814\u7a76\u306f\u3001\u300c\u3044\u3064\u904b\u52d5\u3059\u308b\u304b\u300d\u3068\u3044\u3046\u6642\u9593\u8ef8\u304c\u3001\u9aa8\u683c\u7b4b\u304b\u3089\u5206\u6ccc\u3055\u308c\u308bEV miRNA\u3092\u4ecb\u3057\u305f\u81d3\u5668\u9593\u30b3\u30df\u30e5\u30cb\u30b1\u30fc\u30b7\u30e7\u30f3\u306b\u5f71\u97ff\u3092\u4e0e\u3048\u308b\u53ef\u80fd\u6027\u3092\u793a\u3059\u57fa\u790e\u7684\u77e5\u898b\u3092\u63d0\u4f9b\u3057\u307e\u3059\u3002\u5c06\u6765\u7684\u306b\u306f\u3001\u904b\u52d5\u306e\u30bf\u30a4\u30df\u30f3\u30b0\u3092\u8003\u616e\u3057\u305f\u904b\u52d5\u51e6\u65b9\u304c\u3001\u80a5\u6e80\u3084\u30a4\u30f3\u30b9\u30ea\u30f3\u62b5\u6297\u6027\u306a\u3069\u4ee3\u8b1d\u6027\u75be\u60a3\u306e\u4e88\u9632\u30fb\u6539\u5584\u306b\u5411\u3051\u305f\u65b0\u305f\u306a\u6226\u7565\u3068\u306a\u308b\u53ef\u80fd\u6027\u304c\u3042\u308a\u307e\u3059\u3002<\/p>\n
This study provides foundational evidence that the timing of exercise may influence interorgan communication mediated by muscle-derived EV miRNAs. In the future, exercise timing could become an important variable in exercise prescription strategies aimed at preventing or improving metabolic conditions such as obesity and insulin resistance.<\/p>\n
\u672c\u7814\u7a76\u306f\u30b5\u30f3\u30d7\u30eb\u30b5\u30a4\u30ba\u304c\u5c11\u306a\u304f\uff08\u5404\u7fa43\u53cd\u5fa9\uff09\u3001\u63a2\u7d22\u7684\u306a\u4f4d\u7f6e\u3065\u3051\u3067\u3042\u308b\u305f\u3081\u3001\u4eca\u5f8c\u306f\u3088\u308a\u5927\u898f\u6a21\u306a\u72ec\u7acb\u30b3\u30db\u30fc\u30c8\u3067\u306e\u5b9a\u91cfPCR\u203b7\u306b\u3088\u308b\u691c\u8a3c\u304c\u5fc5\u8981\u3067\u3059\u3002\u307e\u305f\u3001\u96c4\u30de\u30a6\u30b9\u306e\u307f\u3092\u5bfe\u8c61\u3068\u3057\u3066\u3044\u308b\u305f\u3081\u3001\u7cfb\u7d71\u30fb\u5e74\u9f62\u30fb\u6027\u5dee\u3092\u8003\u616e\u3057\u305f\u691c\u8a0e\u3084\u3001\u6a19\u6e96\u98df\u3068\u306e\u6bd4\u8f03\u3001EV\u306e\u6a5f\u80fd\u7684\u306a\u691c\u8a3c\uff08\u53d7\u5bb9\u7d44\u7e54\u306b\u304a\u3051\u308b\u5b9f\u969b\u306e\u4f5c\u7528\uff09\u3082\u4eca\u5f8c\u306e\u8ab2\u984c\u3067\u3059\u3002<\/p>\n
Because this study used a small sample size (n = 3 per group) and was exploratory in nature, future work should validate these findings by qRT-PCR in larger, independent cohorts. As only male mice were used, further studies considering strain, age, and sex differences, comparisons with a standard diet, and functional validation of EV effects in recipient tissues are also needed.<\/p>\n
\u672c\u7814\u7a76\u306b\u53d6\u308a\u7d44\u3080\u4e2d\u3067\u3001\u300c\u3044\u3064\u904b\u52d5\u3059\u308b\u304b\u300d\u304c\u300c\u3069\u3046\u904b\u52d5\u3059\u308b\u304b\u300d\u3068\u540c\u3058\u304f\u3089\u3044\u91cd\u8981\u304b\u3082\u3057\u308c\u306a\u3044\u3068\u3044\u3046\u77e5\u898b\u306b\u5f37\u304f\u60f9\u304b\u308c\u307e\u3057\u305f\u3002\u9aa8\u683c\u7b4b\u7531\u6765\u306eEV\u304c\u3053\u306e\u6642\u9593\u60c5\u5831\u3092\u5168\u8eab\u306b\u4f1d\u3048\u308b”\u30e1\u30c3\u30bb\u30f3\u30b8\u30e3\u30fc”\u3067\u3042\u308b\u53ef\u80fd\u6027\u3092\u793a\u305b\u305f\u3053\u3068\u306f\u3001\u5927\u304d\u306a\u3084\u308a\u304c\u3044\u3067\u3057\u305f\u3002\u307e\u3060\u57fa\u790e\u7684\u306a\u6bb5\u968e\u3067\u3059\u304c\u3001\u5c06\u6765\u7684\u306b\u306f\u3053\u3046\u3057\u305f\u77e5\u898b\u304c\u3001\u3088\u308a\u52b9\u679c\u7684\u3067\u500b\u5225\u5316\u3055\u308c\u305f\u904b\u52d5\u30fb\u6804\u990a\u6307\u5c0e\u3078\u3068\u3064\u306a\u304c\u308b\u3053\u3068\u3092\u671f\u5f85\u3057\u3066\u3044\u307e\u3059\u3002<\/p>\n
While working on this project, I became deeply drawn to the idea that “when” you exercise may matter just as much as “how” you exercise. Being able to show that muscle-derived EVs may act as messengers carrying this timing information throughout the body was genuinely rewarding. Although this remains an exploratory, foundational study, I hope these findings will eventually contribute to more effective, personalized exercise and nutrition guidance.<\/p>\n
\u203b1\u3000\u6982\u65e5\u30ea\u30ba\u30e0<\/p>\n
\u4f53\u5185\u6642\u8a08\u306b\u3088\u3063\u3066\u7d0424\u6642\u9593\u5468\u671f\u3067\u8abf\u7bc0\u3055\u308c\u308b\u751f\u7406\u7684\u306a\u30ea\u30ba\u30e0\u306e\u3053\u3068\u3067\u3059\u3002<\/p>\n
\u203b2\u3000\u7d30\u80de\u5916\u5c0f\u80de\uff08EV\uff09<\/p>\n
\u7d30\u80de\u304b\u3089\u5206\u6ccc\u3055\u308c\u308b\u819c\u3067\u8986\u308f\u308c\u305f\u5fae\u5c0f\u306a\u7c92\u5b50\u3067\u3001\u30bf\u30f3\u30d1\u30af\u8cea\u3084miRNA\u306a\u3069\u3092\u542b\u307f\u3001\u7d30\u80de\u9593\u306e\u60c5\u5831\u4f1d\u9054\u3092\u62c5\u3063\u3066\u3044\u307e\u3059\u3002<\/p>\n
\u203b3\u3000\u30de\u30a4\u30af\u30edRNA\uff08miRNA\uff09<\/p>\n
\u907a\u4f1d\u5b50\u306e\u50cd\u304d\u3092\u8abf\u7bc0\u3059\u308b\u5c0f\u3055\u306aRNA\u5206\u5b50\u3067\u3001\u6a19\u7684\u3068\u306a\u308bmRNA\u306b\u7d50\u5408\u3057\u3066\u30bf\u30f3\u30d1\u30af\u8cea\u5408\u6210\u3092\u6291\u5236\u3057\u307e\u3059\u3002<\/p>\n
\u203b4\u3000\u4e3b\u6210\u5206\u5206\u6790\uff08PCA\uff09
\n\u5927\u91cf\u306e\u30c7\u30fc\u30bf\u304c\u6301\u3064\u8907\u96d1\u306a\u7279\u5fb4\u3092\u3001\u3044\u304f\u3064\u304b\u306e\u4ee3\u8868\u7684\u306a”\u8ef8”\u306b\u307e\u3068\u3081\u3066\u5206\u304b\u308a\u3084\u3059\u304f\u53ef\u8996\u5316\u3059\u308b\u7d71\u8a08\u624b\u6cd5\u3067\u3059\u3002<\/p>\n
\u203b5\u3000miRNA\u30d5\u30a1\u30df\u30ea\u30fc
\n\u5869\u57fa\u914d\u5217\u3084\u6a5f\u80fd\u304c\u4f3c\u3066\u3044\u308b\u8907\u6570\u306emiRNA\u3092\u307e\u3068\u3081\u305f\u30b0\u30eb\u30fc\u30d7\u306e\u3053\u3068\u3067\u3059\u3002<\/p>\n
\u203b6\u3000GO\u30fbKEGG\u89e3\u6790
\n\u591a\u6570\u306e\u907a\u4f1d\u5b50\u304c\u95a2\u308f\u308b\u751f\u7269\u5b66\u7684\u306a\u6a5f\u80fd\uff08GO\uff09\u3084\u3001\u4ee3\u8b1d\u30fb\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u306e\u7d4c\u8def\uff08KEGG\uff09\u3092\u5206\u985e\u30fb\u6574\u7406\u3059\u308b\u305f\u3081\u306e\u89e3\u6790\u624b\u6cd5\u3067\u3059\u3002<\/p>\n
\u203b7\u3000\u5b9a\u91cfPCR
\n\u907a\u4f1d\u5b50\u306e\u767a\u73fe\u91cf\u3092\u6b63\u78ba\u306b\u6e2c\u5b9a\u3059\u308b\u305f\u3081\u306e\u5b9f\u9a13\u6280\u8853\u3067\u3059\u3002<\/p>\n
\u96d1\u8a8c\u540d\uff0fJournal\uff1aNutrients 2026, 18(7), 1076<\/p>\n
\u8ad6\u6587\u540d\uff0fTitle\uff1aCircadian Phase Shapes Muscle-Derived Extracellular Vesicle microRNA Profiles with Context-Dependent Modulation by Exercise in High-Fat-Diet-Fed Mice<\/p>\n
\u57f7\u7b46\u8005\u540d\u30fb\u6240\u5c5e\u6a5f\u95a2\u540d\uff0fAuthors and Affiliated Organisation\uff1aShuo Wang\uff08\u65e9\u7a32\u7530\u5927\u5b66\uff0fWaseda University\uff09\u3001Noriaki Kawanishi\uff08\u5343\u8449\u5de5\u696d\u5927\u5b66\uff0fChiba Institute of Technology\uff09\u3001Cong Wu\uff08\u65e9\u7a32\u7530\u5927\u5b66\uff0fWaseda University\uff09\u3001Haruki Kobori\uff08\u65e9\u7a32\u7530\u5927\u5b66\uff0fWaseda University\uff09\u3001Katsuhiko Suzuki<\/a>\uff08\u65e9\u7a32\u7530\u5927\u5b66\uff0fWaseda University\uff09<\/p>\n Publishment Date\uff08Local Time\uff09\uff1a27th March, 2026<\/p>\n Publishment Date\uff08Japan Time\uff09\uff1a27th March, 2026<\/p>\n \uff08\u30aa\u30f3\u30e9\u30a4\u30f3\u63b2\u8f09\u306e\u5834\u5408\uff0fFor online publication\uff09<\/p>\n URL\uff1ahttps:\/\/www.mdpi.com\/article\/10.3390\/nu18071076<\/a><\/p>\n