DataVXAdvanced SciencePaper
journal article·2026-02Open access

Exclusive Breastfeeding Drives AMPK‐Dependent Thermogenic Memory in BAT and Promotes Long‐Term Metabolic Benefits in Offspring

Ningxi Wu, Anwen Yin, Xiang Yu, Mingxin Wang, Jiahui Zhang, Kerong Liu, Yutong Hou, Minkai Cao, Yiting Zhang, Xiaoxiao Zhang, Yao Gao, Xirong Guo, Le Zhang, Yun Li

Advanced Science· Volume 13· Issue 12
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Source abstract

Abstract

Abstract Exclusive breastfeeding reduces the risk of childhood obesity, potentially through metabolic programming of adipose tissue during lactation. However, the underlying mechanisms remain unclear. Using a mouse model, it is shown that mixed formula feeding disrupts brown adipose tissue (BAT) morphology, mitochondrial integrity, and thermogenic capacity, resulting in greater fat accumulation and glucose intolerance after weaning under a high‐fat diet. By contrast, BAT from exclusively breastfed mice preserved enhanced thermogenic function for up to 12 weeks after transplantation into recipient mice. Transcriptomic analysis revealed that AMPK activation is sustained in BAT from exclusively breastfed mice but markedly diminished in mixed‐fed counterparts. Pharmacological inhibition of AMPK abolished the long‐term metabolic benefits conferred by exclusive breastfeeding. Mechanistically, breast milk–derived extracellular vesicles enriched in miR‐125a‐5p enhanced AMPK signaling by targeting HIF1AN. AMPK‐induced α‐ketoglutarate (αKG) production proved essential for BAT development and thermogenesis, and αKG supplementation rescued impaired BAT function in mixed‐fed mice. In conclusion, exclusive breastfeeding imprints a thermogenic memory in BAT via the HIF1AN/AMPK/αKG signaling axis, thereby conferring long‐term metabolic protection to offspring.
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Research context

OpenAlex topics: Adipose Tissue and Metabolism · Adipokines, Inflammation, and Metabolic Diseases · Regulation of Appetite and Obesity

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pediatric Laboratory Affiliated Children's Hospital of Jiangnan University Wuxi Children's Hospital Wuxi Key Laboratory of Genetic and Metabolic Diseases in Children Wuxi Jiangsu 214023 China

Department of Neonatology Affiliated Children's Hospital of Jiangnan University Wuxi Children's Hospital Wuxi Jiangsu 214023 China

Department of Cardiology The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi People's Hospital Wuxi Medical Center Nanjing Medical University Wuxi Jiangsu 214023 China

Department of Biochemistry and Molecular Cell Biology Shanghai Key Laboratory for Tumor Microenvironment and Inflammation Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Department of Endocrinology Affiliated Children's Hospital of Jiangnan University Wuxi Children's Hospital Wuxi Jiangsu 214023 China

Department of Obstetrics and Gynecology Affiliated Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital Wuxi Jiangsu 214002 China

Department of Endocrinology Children's Hospital of Nanjing Medical University Nanjing Jiangsu 210008 China

Hongqiao International Institute of Medicine Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200336 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · China Postdoctoral Science Foundation

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