Drinking water temperatures modulate gut microbiota-L-cysteine axis to enhance adipose thermogenesis and alleviate obesity-related metabolic disorders in mice

  • Life Sci. 2026 Jul 15:397:124438. doi: 10.1016/j.lfs.2026.124438.
Huiting Wang  1 ,  Tianyu Li  1 ,  Jiyuan Yang  1 ,  Wenxiang Zhang  2 ,  Siyu Chen  2 ,  Mingming Song  3 ,  Shuiming Wang  4 ,  Chang Liu  5
Affiliations
  • 1. Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, 211198, China; State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China; Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, 211198, China.
  • 2. Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, 211198, China.
  • 3. School of Pharmaceutical Sciences, Anhui Medical University, Hefei, 230032, China.
  • 4. Department of Proctology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210022, China. Electronic address: [email protected].
  • 5. Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, 211198, China; State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China; Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, 211198, China. Electronic address: [email protected].
PMID: 42097400 DOI: 10.1016/j.lfs.2026.124438
Abstract

Aims: Although people living in different countries prefer to drink water at various temperatures, the influence of drinking water temperature on metabolic homeostasis remains largely unexplored. This study investigated how different drinking-water temperatures affect metabolic regulation and the underlying gut microbiota-metabolite interactions.

Materials and methods: High-fat diet (HFD)-fed mice were given water at 0 °C, 25 °C, or 40 °C. Metabolic alterations were assessed by histopathology, serum biochemistry, and body-composition analysis, with food intake and core temperature monitored. Gut microbiota causality was examined using Antibiotic depletion and reciprocal fecal microbiota transplantation (FMT). 16S rRNA gene Sequencing and metabolomics were performed to characterize fecal microbial and metabolite profiles. Adipose stromal vascular fraction (SVF) cells were used in vitro to examine the effects of L-cysteine on lipid metabolism.

Key findings: Both 0 °C and 40 °C water ameliorated HFD-induced metabolic dysfunction through increased energy expenditure, reduced liver steatosis, and enhanced adipose-tissue thermogenesis, independent of differences in intake. Cold water selectively enriched Bifidobacterium pseudolongum and Adlercreutzia equolifaciens, whereas warm water increased Bacteroides acidifaciens, Alistipes inops and Alistipes obesi, indicating distinct microbiota configurations. Antibiotic ablation blunted these benefits, while cross-group FMT reproduced the metabolic and thermogenic phenotypes, confirming a microbiota-dependent mechanism. Despite divergent microbiota structures, both temperature regimens consistently elevated L-cysteine, which reduced lipid accumulation and enhanced thermogenic gene expression in SVF cells.

Significance: These findings highlight drinking-water temperature as a simple, safe, and sustainable lifestyle factor with translational potential to mitigate obesity-related metabolic dysfunction, potentially via a gut microbiota-L-cysteine axis that enhances adipose thermogenesis and systemic metabolic homeostasis.

Keywords
Drinking water temperature; Gut microbiota; L-cysteine; Metabolic disorder; Thermogenesis.
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