| 1. |
- Arner, P., et al.
(författare)
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Adipose lipid turnover and long-term changes in body weight
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:9, s. 1385-1389
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Tidskriftsartikel (refereegranskat)abstract
- The worldwide obesity epidemic(1) makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates(2,3). Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived C-14 in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.
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| 2. |
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| 3. |
- Hagberg, C. E., et al.
(författare)
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Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and Cellular Heterogeneity
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 24:10
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Tidskriftsartikel (refereegranskat)abstract
- Adipocytes, once considered simple lipid-storing cells, are rapidly emerging as complex cells with many biologically diverse functions. A powerful high-throughput method for analyzing single cells is flow cytometry. Several groups have attempted to analyze and sort freshly isolated adipocytes; however, using an adipocyte-specific reporter mouse, we demonstrate that these studies fail to detect the majority of white adipocytes. We define critical settings required for adipocyte flow cytometry and provide a rigid strategy for analyzing and sorting white and brown adipocyte populations. The applicability of our protocol is shown by sorting mouse adipocytes based on size or UCP1 expression and demonstrating that a subset of human adipocytes lacks the beta(2)-adrenergic receptor, particularly in the insulin-resistant state. In conclusion, the present study confers key technological insights for analyzing and sorting mature adipocytes, opening up numerous downstream research applications.
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| 4. |
- Harms, M. J., et al.
(författare)
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Mature Human White Adipocytes Cultured under Membranes Maintain Identity, Function, and Can Transdifferentiate into Brown-like Adipocytes
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- White adipose tissue (WAT) is a central factor in the development of type 2 diabetes, but there is a paucity of translational models to study mature adipocytes. We describe a method for the culture of mature white adipocytes under a permeable membrane. Compared to existing culture methods, MAAC (membrane mature adipocyte aggregate cultures) better maintain adipogenic gene expression, do not dedifferentiate, display reduced hypoxia, and remain functional after long-term culture. Subcutaneous and visceral adipocytes cultured as MAAC retain depot-specific gene expression, and adipocytes from both lean and obese patients can be cultured. Importantly, we show that rosiglitazone treatment or PGC1 alpha overexpression in mature white adipocytes induces a brown fat transcriptional program, providing direct evidence that human adipocytes can transdifferentiate into brown-like adipocytes. Together, these data show that MAAC are a versatile tool for studying phenotypic changes of mature adipocytes and provide an improved translational model for drug development.
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| 5. |
- Spalding, KL, et al.
(författare)
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Impact of fat mass and distribution on lipid turnover in human adipose tissue
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15253-
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Tidskriftsartikel (refereegranskat)abstract
- Differences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. Here we compare triglyceride age and, thereby, triglyceride turnover in vWAT and sWAT biopsies from 346 individuals and find that subcutaneous triglyceride age and storage capacity are increased in overweight or obese individuals. Visceral triglyceride age is only increased in excessively obese individuals and associated with a lower lipid removal capacity. Thus, although triglyceride storage capacity in sWAT is higher than in vWAT, the former plateaus at substantially lower levels of excess WAT mass than vWAT. In individuals with central or visceral obesity, lipid turnover is selectively increased in vWAT. Obese individuals classified as ‘metabolically unhealthy’ (according to ATPIII criteria) who have small subcutaneous adipocytes exhibit reduced triglyceride turnover. We conclude that excess WAT results in depot-specific differences in lipid turnover and increased turnover in vWAT and/or decreased turnover in sWAT may result in metabolic complications of overweight or obesity.
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