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The Aging Adipose Organ: Lipid Redistribution, Inflammation, and Cellular Senescence

Published on Jan 1, 2014
· DOI :10.1007/978-1-62703-770-9_5
Michael B. Stout14
Estimated H-index: 14
Tamara Tchkonia41
Estimated H-index: 41
James L. Kirkland5
Estimated H-index: 5
White adipose tissue (WAT) is an immensely plastic organ that plays a vital role in regulating metabolic homeostasis and systemic inflammation. Advancing age mitigates the dynamic nature of WAT which promotes the manifestation of several lipodystrophic-associated comorbidities. Inflammation and the accumulation of senescence cells likely play a key role in this process by inhibiting adipogenesis. The reduction of WAT functional capacity with aging and the role that inflammation and cellular senescence may play in this process will be explored throughout this review.
  • References (132)
  • Citations (3)
Published on Feb 1, 2012in Cell Metabolism 20.57
Khanh-Van Tran2
Estimated H-index: 2
(University of Massachusetts Medical School),
Olga Gealekman7
Estimated H-index: 7
(University of Massachusetts Medical School)
+ 9 AuthorsAndrea Sbarbati42
Estimated H-index: 42
Summary Adipose tissue expansion involves the enlargement of existing adipocytes, the formation of new cells from committed preadipocytes, and the coordinated development of the tissue vascular network. Here we find that murine endothelial cells (ECs) of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes. Lineage tracing experiments using the VE-cadherin promoter reveal localization of repo...
220 Citations Source Cite
Published on Jan 1, 2012in Diabetes Care 13.40
Julia P. Dunn6
Estimated H-index: 6
Naji N. Abumrad46
Estimated H-index: 46
+ 5 AuthorsRobyn A. Tamboli12
Estimated H-index: 12
OBJECTIVE Early after Roux-en-Y gastric bypass (RYGB), there is improvement in type 2 diabetes, which is characterized by insulin resistance. We determined the acute effects of RYGB, with and without omentectomy, on hepatic and peripheral insulin sensitivity. We also investigated whether preoperative diabetes or postoperative diabetes remission influenced tissue-specific insulin sensitivity after RYGB. RESEARCH DESIGN AND METHODS We studied 40 obese (BMI 48 ± 8 kg/m 2 ) participants, 17 with dia...
83 Citations Source Cite
Published on Jan 1, 2012in Physiological Reviews 24.01
Dylan Thompson28
Estimated H-index: 28
Fredrik Karpe67
Estimated H-index: 67
+ 1 AuthorsKeith N. Frayn64
Estimated H-index: 64
Physical activity and exercise are key components of energy expenditure and therefore of energy balance. Changes in energy balance alter fat mass. It is therefore reasonable to ask: What are the links between physical activity and adipose tissue function? There are many complexities. Physical activity is a multifaceted behavior of which exercise is just one component. Physical activity influences adipose tissue both acutely and in the longer term. A single bout of exercise stimulates adipose tis...
150 Citations Source Cite
Published on Nov 1, 2011in Nature 41.58
Darren J. Baker30
Estimated H-index: 30
(Mayo Clinic),
Tobias Wijshake6
Estimated H-index: 6
(Mayo Clinic)
+ 5 AuthorsJ.M.A. van Deursen57
Estimated H-index: 57
(Mayo Clinic)
Senescent cells accumulate in tissues with age, but it is not known whether they actually cause age-related dysfunction or whether their removal is beneficial. Using a mouse model with a transgene named INK-ATTAC, which allows for the inducible elimination of cells carrying the senescence biomarker p16Ink4a, Baker et al. demonstrate that life-long removal of senescent cells delays the onset of age-related phenotypes. Furthermore, late-life clearance attenuated the progression of already establis...
1,172 Citations Source Cite
Abhimanyu Garg63
Estimated H-index: 63
(University of Texas Southwestern Medical Center)
Context: Lipodystrophies are heterogeneous, genetic or acquired disorders characterized by selective loss of body fat and predisposition to insulin resistance. The extent of fat loss determines the severity of associated metabolic complications such as diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Evidence Acquisition and Synthesis: Both original and review articles were found via PubMed search reporting on clinical features and management of various types of lipodystrophies an...
274 Citations Source Cite
Published on Feb 1, 2011in Nature Reviews Immunology 41.98
Noriyuki Ouchi68
Estimated H-index: 68
(Nagoya University),
Jennifer L. Parker4
Estimated H-index: 4
(Boston University)
+ 1 AuthorsKenneth Walsh94
Estimated H-index: 94
(Boston University)
Adipose tissues and infiltrating immune cells produce numerous bioactive factors that have pro-inflammatory or anti-inflammatory activities. Here, the authors describe how dysregulated production of these so-called adipokines can contribute to the pathogenesis of obesity-linked metabolic disease.
1,800 Citations Source Cite
Published on Dec 1, 2010in Obesity 4.04
Annemarie Koster45
Estimated H-index: 45
(Maastricht University),
Sari Stenholm28
Estimated H-index: 28
(National Institute for Health and Welfare)
+ 11 AuthorsFrances A. Tylavsky59
Estimated H-index: 59
(University of Tennessee)
The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI 30kg/m 2), aged 70-79 participating in the Health, Aging a...
128 Citations Source Cite
Published on Oct 1, 2010in Aging Cell 7.63
Tamara Tchkonia41
Estimated H-index: 41
(Mayo Clinic),
Dean E. Morbeck14
Estimated H-index: 14
(Mayo Clinic)
+ 6 AuthorsJames L. Kirkland53
Estimated H-index: 53
(Mayo Clinic)
Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdif...
379 Citations Source Cite
Published on Aug 4, 2010in FEBS Letters 3.00
Arjen Koppen11
Estimated H-index: 11
Eric Kalkhoven40
Estimated H-index: 40
The development of adipose tissue is a process which involves the concerted cooperation of numerous transcription factors together with their coactivators and corepressors. The peroxisome proliferator-activated receptor γ (PPARγ) is considered to be one of the master regulators of adipocyte differentiation. The presence of two functionally distinct types of adipose tissue, white and brown (WAT and BAT), requires an even more complex regulation of adipose tissue development. In this review we wil...
82 Citations Source Cite
Published on Aug 1, 2010in Gastroenterology 20.77
Elisa Fabbrini23
Estimated H-index: 23
(Washington University in St. Louis),
Robyn A. Tamboli12
Estimated H-index: 12
(Vanderbilt University)
+ 5 AuthorsNaji N. Abumrad46
Estimated H-index: 46
(Vanderbilt University)
Background & Aims Visceral adipose tissue (VAT) is an important risk factor for the metabolic complications associated with obesity. Therefore, a reduction in VAT is considered an important target of obesity therapy. We evaluated whether reducing VAT mass by surgical removal of the omentum improves insulin sensitivity and metabolic function in obese patients. Methods We conducted a 12-month randomized controlled trial to determine whether reducing VAT by omentectomy in 22 obese subjects increase...
138 Citations Source Cite
Cited By3
Michael B. Stout14
Estimated H-index: 14
(Mayo Clinic),
Frederik J. Steyn18
Estimated H-index: 18
(University of Queensland)
+ 21 AuthorsTamar Pirtskhalava23
Estimated H-index: 23
(Mayo Clinic)
Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17α-estradiol (17α-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in ener...
28 Citations Source Cite
Asael Roichman2
Estimated H-index: 2
(Bar-Ilan University),
Yariv Kanfi10
Estimated H-index: 10
(Bar-Ilan University)
+ 8 AuthorsJonathan Leor47
Estimated H-index: 47
(Sheba Medical Center)
Abstract The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD(+) dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evalua...
9 Citations Source Cite
Published on Dec 1, 2014in Biogerontology 3.70
Yossi Ovadya11
Estimated H-index: 11
(Weizmann Institute of Science),
Valery Krizhanovsky23
Estimated H-index: 23
(Weizmann Institute of Science)
The progression of physiological ageing is driven by intracellular aberrations including telomere attrition, genomic instability, epigenetic alterations and loss of proteostasis. These in turn damage cells and compromise their functionality. Cellular senescence, a stable irreversible cell-cycle arrest, is elicited in damaged cells and prevents their propagation in the organism. Under normal conditions, senescent cells recruit the immune system which facilitates their removal from tissues. Nevert...
78 Citations Source Cite