Fan Rong, Story Galaxie, Kim Judy, Li Zhuoheng, Bannon Sean T, Cho Hyunji, Ranjan Ravi, Kim Young-Cheul, Layec Gwenael, Chung Soonkyu
Department of Nutrition, University of Massachusetts, Amherst, Massachusetts, USA.
Department of Food Science, University of Massachusetts, Amherst, Massachusetts, USA.
Acta Physiol (Oxf). 2025 Apr;241(4):e70025. doi: 10.1111/apha.70025.
Aging decreases the metabolic rate and increases the risk of metabolic diseases, highlighting the need for alternative strategies to improve metabolic health. Heat treatment (HT) has shown various metabolic benefits, but its ability to counteract aging-associated metabolic slowdown remains unclear. This study aimed to investigate the impact of whole-body HT on energy metabolism, explore the potential mechanism involving the heat sensor TRPV1, and examine the modulation of gut microbiota.
Ten-month-old female C57BL/6 mice on a high-fat (HF) diet (45% calories from fat) were exposed to daily HT in a 40-41°C heat chamber for 30 min, 5 days a week for 6 weeks. Metabolic changes, including core body temperature and lipid metabolism transcription in adipose tissue and liver, were assessed. Human brown adipocytes were used to confirm metabolic effects in vitro.
HT significantly reduced serum lactate dehydrogenase levels, indicating mitigation of tissue damage. HT attenuated weight gain, improved insulin sensitivity, and increased beta-oxidation in the liver and brown fat. In thermogenic adipose tissue, HT enhanced TRPV1 and Ca/ATPase pump expression, suggesting ATP-dependent calcium cycling, which was confirmed in human brown adipocytes. Interestingly, HT also reduced the firmicutes/bacteroides ratio and altered gut microbiota, suppressing HF diet-enriched microbial genera such as Tuzzerella, Defluviitaleaceae_UCG-011, Alistipes, and Enterorhabdus.
HT attenuates aging- and diet-associated metabolic slowdown by increasing futile calcium cycling, enhancing energy expenditure, and altering gut microbiota in middle-aged female C57BL/6 mice. HT may offer a promising strategy to improve metabolic health, especially in aging populations.
衰老会降低代谢率并增加代谢性疾病的风险，这凸显了需要采用替代策略来改善代谢健康。热处理（HT）已显示出多种代谢益处，但其抵消与衰老相关的代谢减缓的能力仍不清楚。本研究旨在调查全身热处理对能量代谢的影响，探索涉及热传感器TRPV1的潜在机制，并研究肠道微生物群的调节情况。
将10月龄高脂（HF）饮食（45%热量来自脂肪）的雌性C57BL/6小鼠置于40-41°C的热室中，每天进行30分钟的热处理，每周5天，持续6周。评估包括核心体温以及脂肪组织和肝脏中脂质代谢转录在内的代谢变化。使用人棕色脂肪细胞在体外确认代谢效应。
热处理显著降低了血清乳酸脱氢酶水平，表明组织损伤得到缓解。热处理减轻了体重增加，改善了胰岛素敏感性，并增加了肝脏和棕色脂肪中的β-氧化。在产热脂肪组织中，热处理增强了TRPV1和Ca/ATPase泵的表达，提示ATP依赖的钙循环，这在人棕色脂肪细胞中得到了证实。有趣的是，热处理还降低了厚壁菌门/拟杆菌门的比例并改变了肠道微生物群，抑制了高脂饮食富集的微生物属，如土氏菌属、脱卤杆菌科_UCG-011、艾氏杆菌属和肠道杆状菌属。
在中年雌性C57BL/6小鼠中，热处理通过增加无效钙循环、增强能量消耗和改变肠道微生物群来减轻与衰老和饮食相关的代谢减缓。热处理可能为改善代谢健康提供一种有前景的策略，尤其是在老年人群中。
