Student Theses and Dissertations
Date of Award
2025
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Paul Cohen
Keywords
beige adipocytes, thermogenesis, thyroid hormone, adipose tissue, obesity, macrophages
Abstract
Obesity has become a major global health concern, with the number of individuals affected rising dramatically over the past several decades. Obesity is closely linked to a range of chronic diseases and contributes significantly to morbidity and mortality worldwide. Adipose tissue lies at the center of this issue. However, it is increasingly recognized that it is the quality of fat, rather than its quantity alone, that has a greater impact on metabolic health. While excess accumulation of lipid-storing white adipocytes is usually associated with metabolic complications, brown and beige adipocytes, specialized cell types that disspate energy through heat production, are associated with beneficial outcomes, including increased energy expenditure, improved glucose and lipid metabolism, and reduced odds of type 2 diabetes, hypertension, hyperlipidemia, and cardiovascular disease. These metabolic advantages make thermogenic adipocytes promising therapeutic targets for obesity and associated diseases. A deeper understanding of these cells could provide valuable insights for the development of more effective treatments for metabolic disease. In this study, we explored the multifaceted life of beige adipocytes. We charted their life trajectory from their emergence in early life to their persistence and function in adulthood. We found that beige adipocytes first emerge in life in a temperature-independent manner during the postnatal period. They later lose thermogenic activity as mice mature, but can be reactivated upon cold stimulation, contributing to the majority of beige adipocytes found in adult animals. Upon prolonged cold exposure, a small group of beige adipocytes can also emerge de novo. Focusing on the postnatal window, we identified ICAM1+/IL1R1+ committed preadipocytes as the precursors of postnatal beige adipocytes. This cell type appears to be bipotential, capable of giving rise to both beige and white adipocytes. Their thermogenic fate is primarily driven by a postnatal surge in circulating thyroid hormone, likely mediated through thyroid hormone receptor beta. We also revealed that macrophages can accelerate the lineage progression of these progenitor cells and increase the abundance of beige precursor cells. In adulthood, we examined the function and transcriptional profile of inactive beige adipocytes in both lean and obese animals. We found that inactive beige adipocytes persist within adipose tissue, even after long-term high-fat diet feeding. Although morphologically similar to white adipocytes and lacking thermogenic gene expression, inactive beige adipocytes exhibit distinct transcriptional profiles compared to classical white adipocytes. Functionally, we discovered that inactive beige adipocytes are linked to a lower occurrence of crown-like structures during obesity, a hallmark typically associated with chronic inflammation in white adipose tissue. This functional difference between inactive beige and white adipocytes is dependent on CCR2-mediated monocyte-recruitment, likely triggered by extracellular matrix remodeling driven by local adipocyte subtypes. Together, our findings offer important insights into the developmental and functional complexity of beige adipocytes, from their origins and molecular identity to their role in shaping the tissue microenvironment. This deeper understanding of beige adipocyte biology provides a foundation for developing new strategies to target this cell type in obesity and comorbid diseases.
License and Reuse Information
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Lin, Zeran, "Exploring the Multifaceted Life of Beige Adipocytes" (2025). Student Theses and Dissertations. 812.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/812
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy