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Adipose Tissue Plasticity in Aging

Guan Wang, Anying Song, Marie Bae, Qiong A. Wang

10.1002/cphy.c220005

Source: Volume 12, Issue 4, October 2022

Published online: October 2022

Full Article on Wiley Online Library



Abstract

As a dynamic endocrine organ, white adipose tissue (WAT) stores lipids and plays a critical role in maintaining whole‐body energy homeostasis and insulin sensitivity. A large group of the population over 65 years old suffer from increased WAT mass, especially in the visceral location. Visceral adiposity accelerates aging through promoting age‐associated chronic conditions, significantly shortening life expectancy. Unlike WAT, brown adipose tissue (BAT) functions as an effective energy sink that burns and disposes of excess lipids and glucose upon activation of thermogenesis. Unfortunately, the thermogenic activity of BAT declines during aging. New appreciation of cellular and functional remodeling of WAT and BAT during aging has emerged in recent years. Efforts are underway to explore the potential underlying mechanisms behind these age‐associated alterations in WAT and BAT and the impact of these alterations on whole‐body metabolism. Lastly, it is intriguing to translate our knowledge obtained from animal models to the clinic to prevent and treat age‐associated metabolic disorders. © 2022 American Physiological Society. Compr Physiol 12: 4119–4132, 2022.

Figure 1. Figure 1. Age‐associated adipose tissue dysfunction. Adipose tissue undergoes redistribution during aging, with accumulation of vWAT and reduction in sWAT. Concurrently, skeletal muscle mass decreases, and ectopic adipose deposition increases. Thermogenic activity of BAT declines with age. Brown adipocyte heterogeneity alters during aging as the low‐thermogenic brown adipocytes dramatically increases in number. In WAT, especially in vWAT, aging is associated with increased cellular senescence, hypoxia, and chronic inflammation. These changes impair the function of WAT. Dysfunctional WAT and BAT contribute to metabolic disorders, which accelerate the aging process. Created with BioRender.com.
Figure 2. Figure 2. Adipocyte progenitor plasticity in WAT during aging. DPP4+ ASCs and ICAM1+ preadipocytes exist in sWAT and vWAT, which differentiate into mature adipocytes. In young sWAT, CD142+ Aregs inhibit adipogenesis. Some studies also indicate that this population could be converted to ICAM1+ preadipocytes and differentiate into adipocytes. In aged sWAT, Lgals3+CD36+ ARC population emerges with age, which could inhibit adipogenesis of the neighboring APCs. Lineage trajectory shows that the ARC population derived from ICAM1+Pref1+ preadipocytes. Further evidence is needed to demonstrate the regulatory role of CD142+ Aregs during aging. In young vWAT, PDGFRβ+Ly6C+ FIPs inhibit adipogenesis and contribute to inflammation. Their dynamics during aging remain to be determined. A novel preadipocyte population, LIFR+Thbs1+ CP‐A population, contributes to the massive adipogenesis in vWAT during aging. The inhibitory role of FIPs on adipogenesis might be impaired with age, which might be one possible mechanism that unlocks the differentiation capacity of the CP‐A population in aging. Created with BioRender.com.
Figure 3. Figure 3. Immune cell alterations in aged vWAT. In young vWAT, ILC2s are recruited by IL‐33‐producing PDGFRα+ and PDGFRβ+ DPP4+ stromal cells. ILC2s maintain eosinophils through IL‐5 and activate macrophages toward an anti‐inflammatory M2 phenotype through IL‐13. Eosinophils also maintain M2 by secreting IL‐4. The ILC2‐eosinophil‐M2 axis contributes to thermogenesis, tissue homeostasis, physical health, and insulin sensitivity. In aged vWAT, ILC2s are sustained by mesothelial cells and become dysfunctional in a cell‐intrinsic manner. IL‐33‐producing PDGFRα+ stromal cells are responsible for Treg accumulation. Adipocytes have hypertrophy and impaired lipolysis. MAOA‐mediated catecholamine degradation is responsible for impaired lipolysis. MAOA is produced in adipocytes in human and macrophages in mice, which is dependent on Nlrp3 inflammasome. Nlrp3+ macrophages lead to B cell expansion, which could also inhibit lipolysis. The cellular changes in aged vWAT result in increased tissue and systemic inflammation, reduced physical fitness, and insulin resistance. Created with BioRender.com.


Figure 1. Age‐associated adipose tissue dysfunction. Adipose tissue undergoes redistribution during aging, with accumulation of vWAT and reduction in sWAT. Concurrently, skeletal muscle mass decreases, and ectopic adipose deposition increases. Thermogenic activity of BAT declines with age. Brown adipocyte heterogeneity alters during aging as the low‐thermogenic brown adipocytes dramatically increases in number. In WAT, especially in vWAT, aging is associated with increased cellular senescence, hypoxia, and chronic inflammation. These changes impair the function of WAT. Dysfunctional WAT and BAT contribute to metabolic disorders, which accelerate the aging process. Created with BioRender.com.


Figure 2. Adipocyte progenitor plasticity in WAT during aging. DPP4+ ASCs and ICAM1+ preadipocytes exist in sWAT and vWAT, which differentiate into mature adipocytes. In young sWAT, CD142+ Aregs inhibit adipogenesis. Some studies also indicate that this population could be converted to ICAM1+ preadipocytes and differentiate into adipocytes. In aged sWAT, Lgals3+CD36+ ARC population emerges with age, which could inhibit adipogenesis of the neighboring APCs. Lineage trajectory shows that the ARC population derived from ICAM1+Pref1+ preadipocytes. Further evidence is needed to demonstrate the regulatory role of CD142+ Aregs during aging. In young vWAT, PDGFRβ+Ly6C+ FIPs inhibit adipogenesis and contribute to inflammation. Their dynamics during aging remain to be determined. A novel preadipocyte population, LIFR+Thbs1+ CP‐A population, contributes to the massive adipogenesis in vWAT during aging. The inhibitory role of FIPs on adipogenesis might be impaired with age, which might be one possible mechanism that unlocks the differentiation capacity of the CP‐A population in aging. Created with BioRender.com.


Figure 3. Immune cell alterations in aged vWAT. In young vWAT, ILC2s are recruited by IL‐33‐producing PDGFRα+ and PDGFRβ+ DPP4+ stromal cells. ILC2s maintain eosinophils through IL‐5 and activate macrophages toward an anti‐inflammatory M2 phenotype through IL‐13. Eosinophils also maintain M2 by secreting IL‐4. The ILC2‐eosinophil‐M2 axis contributes to thermogenesis, tissue homeostasis, physical health, and insulin sensitivity. In aged vWAT, ILC2s are sustained by mesothelial cells and become dysfunctional in a cell‐intrinsic manner. IL‐33‐producing PDGFRα+ stromal cells are responsible for Treg accumulation. Adipocytes have hypertrophy and impaired lipolysis. MAOA‐mediated catecholamine degradation is responsible for impaired lipolysis. MAOA is produced in adipocytes in human and macrophages in mice, which is dependent on Nlrp3 inflammasome. Nlrp3+ macrophages lead to B cell expansion, which could also inhibit lipolysis. The cellular changes in aged vWAT result in increased tissue and systemic inflammation, reduced physical fitness, and insulin resistance. Created with BioRender.com.
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Article Title: Adipose Tissue Plasticity in Aging
 

How to Cite

Guan Wang, Anying Song, Marie Bae, Qiong A. Wang. Adipose Tissue Plasticity in Aging. Compr Physiol 2022, 12: 4119-4132. doi: 10.1002/cphy.c220005