2. Academic Validation
  3. Estrogen counteracts age-related decline in beige adipogenesis through the NAMPT-regulated ER stress response

Estrogen counteracts age-related decline in beige adipogenesis through the NAMPT-regulated ER stress response

  • Nat Aging. 2024 Jun;4(6):839-853. doi: 10.1038/s43587-024-00633-z.
Jooman Park # 1,  Ruoci Hu # 1 2,  Yanyu Qian 1,  Shaolei Xiong 1 3,  Asma Sana El-Sabbagh 1,  Meram Ibrahim 1,  Jaden Wang 1,  Ziqiao Xu 4,  Zhengjia Chen 4 5,  Qing Song 6,  Zhenyuan Song 6,  Gege Yan 7,  Abeer M Mahmoud 8,  Yanlin He 9,  Brian T Layden 8 10,  Jiwang Chen 11,  Sang-Ging Ong 7 12,  Pingwen Xu 8,  Yuwei Jiang 13 14 15
Affiliations

Affiliations

  • 1 Department of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 2 Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, USA.
  • 3 Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, IL, USA.
  • 4 Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois Chicago, Chicago, IL, USA.
  • 5 Biostatistics Shared Resource, University of Illinois Cancer Center, Chicago, IL, USA.
  • 6 Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA.
  • 7 Department of Pharmacology and Regenerative Medicine, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 8 Division of Endocrinology, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 9 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
  • 10 Jesse Brown Medical VA Medical Center, Chicago, IL, USA.
  • 11 Division of Pulmonary, Critical Care, Sleep & Allergy, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 12 Division of Cardiology, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 13 Department of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA. yuweij@uic.edu.
  • 14 Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, USA. yuweij@uic.edu.
  • 15 Division of Endocrinology, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA. yuweij@uic.edu.
  • # Contributed equally.
PMID: 38858606 DOI: 10.1038/s43587-024-00633-z
Abstract

Thermogenic beige adipocytes are recognized as potential therapeutic targets for combating metabolic diseases. However, the metabolic advantages that they offer are compromised with aging. Here we show that treating mice with estrogen (E2), a hormone that decreases with age, can counteract the age-related decline in beige adipogenesis when exposed to cold temperature while concurrently enhancing energy expenditure and improving glucose tolerance in mice. Mechanistically, we found that nicotinamide phosphoribosyl transferase (NAMPT) plays a pivotal role in facilitating the formation of E2-induced beige adipocytes, which subsequently suppresses the onset of age-related endoplasmic reticulum (ER) stress. Furthermore, we found that targeting NAMPT signaling, either genetically or pharmacologically, can restore the formation of beige adipocytes by increasing the number of perivascular adipocyte progenitor cells. Conversely, the absence of NAMPT signaling prevents this process. Together, our findings shed light on the mechanisms regulating the age-dependent impairment of beige adipocyte formation and underscore the E2-NAMPT-controlled ER stress pathway as a key regulator of this process.

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