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Molecular Control of Adipose Cell Fate and Energy Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 24222

Special Issue Editor


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Guest Editor
Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA
Interests: obesity; diabetes; brown adipose tissue; metabolic disease; thermogenesis; beige adipocytes; mitochondrial homeostasis

Special Issue Information

Dear Colleagues,

Adipose tissues play a central role in energy homeostasis. Metabolic phenotypes of brown (BAT) and white adipose tissues (WAT) vary substantially in response to environmental cues. For instance, cold exposure is the physiological cue for stimulating adipose metabolic thermogenesis and results in BAT hyperplasia and browning of WAT via sympathetic nervous activation in small rodents. These manifestations in adipose thermogenesis not only facilitate the maintenance of body temperature in the cold but also result in the significant reduction of body fat content, improving insulin resistance. The rediscovery of metabolically active BAT in healthy adult humans in 2009 has given impetus to research on human BAT as a potential target to fight obesity and related metabolic diseases such as type 2 diabetes. However, despite several recent studies demonstrating that cold acclimation indeed recruits BAT in healthy humans, the BAT-targeting regimen remains a challenge for researchers and clinicians because chronic cold exposure in daily life is difficult to achieve for obese or diabetic patients owing to its uncomfortability and potential negative effects on cardiovascular function. The investigation and identification of molecular circuits that regulate the fate specification of brown adipocytes or brown-like (beige) adipocytes may lead to an alternative and effective therapeutic intervention targeting adipose tissue thermogenesis to counteract human obesity and metabolic disorders. To this end, more insights are needed into the physiological significance of human BAT and mechanisms by which BAT function is regulated by aging, as well as endogenous and environmental factors.

Thus, here we would like to highlight the current understand of molecular circuits that determine the fate specification of brown adipose cells and to investigate their physiological roles in energy homeostasis both in experimental animals and in humans. We also would like to depict advances in adipose tissue homeostasis and its metabolic implications for inflammation, obesity, as well as links to metabolic diseases.

Dr. Takeshi Yoneshiro
Guest Editor

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Keywords

  • Brown adipose tissue
  • Beige adipose tissue
  • Energy homeostasis
  • Molecular circuits
  • Inflammation
  • Obesity
  • Metabolic diseases

Published Papers (4 papers)

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Research

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21 pages, 5829 KiB  
Article
Regulation of Adipogenesis and Lipid Deposits by Collapsin Response Mediator Protein 2
by Yih-Hsin Chang, Jen-Ning Tsai, Shu-Wen Chang, Wei-Ting Hsu, Ching-Ping Yang, Chiao-Wan Hsiao and Ming-Yuh Shiau
Int. J. Mol. Sci. 2020, 21(6), 2172; https://doi.org/10.3390/ijms21062172 - 21 Mar 2020
Cited by 14 | Viewed by 4765
Abstract
As emerging evidence suggesting neurodegenerative diseases and metabolic diseases have common pathogenesis, we hypothesized that the neurite outgrowth-controlling collapsin response mediator protein 2 (CRMP2) was involved in energy homeostasis. Therefore, putative roles of CRMP2 in adipocyte differentiation (adipogenesis) and lipid metabolism were explored [...] Read more.
As emerging evidence suggesting neurodegenerative diseases and metabolic diseases have common pathogenesis, we hypothesized that the neurite outgrowth-controlling collapsin response mediator protein 2 (CRMP2) was involved in energy homeostasis. Therefore, putative roles of CRMP2 in adipocyte differentiation (adipogenesis) and lipid metabolism were explored and addressed in this study. CRMP2 expression profiles were in vitro and in vivo characterized during adipogenic process of 3T3-L1 pre-adipocytes and diet-induced obese (DIO) mice, respectively. Effects of CRMP2 on lipid metabolism and deposits were also analyzed. Our data revealed that CRMP2 expression pattern was coupled with adipogenic stages. CRMP2 overexpression inhibited cell proliferation at MCE phase, and significantly reduced lipid contents by down-regulating adipogenesis-driving transcription factors and lipid-synthesizing enzymes. Interestingly, GLUT4 translocation and the lipid droplets fusion were disturbed in CRMP2-silencing cells by affecting actin polymerization. Moreover, adipose CRMP2 was significantly increased in DIO mice, indicating CRMP2 is associated with obesity. Accordingly, CRMP2 exerts multiple functions in adipogenesis and lipid deposits through mediating cell proliferation, glucose/lipid metabolism and cytoskeleton dynamics. The present study identifies novel roles of CRMP2 in mediating adipogenesis and possible implication in metabolic disorders, as well as provides molecular evidence supporting the link of pathogenesis between neurodegenerative diseases and metabolic abnormalities. Full article
(This article belongs to the Special Issue Molecular Control of Adipose Cell Fate and Energy Metabolism)
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9 pages, 560 KiB  
Article
Applicability of Supraclavicular Oxygenated and Total Hemoglobin Evaluated by Near-Infrared Time-Resolved Spectroscopy as Indicators of Brown Adipose Tissue Density in Humans
by Shinsuke Nirengi, Sayuri Fuse, Shiho Amagasa, Toshiyuki Homma, Ryotaro Kime, Miyuki Kuroiwa, Tasuki Endo, Naoki Sakane, Mami Matsushita, Masayuki Saito, Yuko Kurosawa and Takafumi Hamaoka
Int. J. Mol. Sci. 2019, 20(9), 2214; https://doi.org/10.3390/ijms20092214 - 6 May 2019
Cited by 7 | Viewed by 2916
Abstract
Brown adipose tissue (BAT) may potentially be used in strategies for preventing lifestyle-related diseases. We examine evidence that near-infrared time-resolved spectroscopy (NIRTRS) is capable of estimating human BAT density (BAT-d). The parameters examined in this study are total hemoglobin [total-Hb]sup [...] Read more.
Brown adipose tissue (BAT) may potentially be used in strategies for preventing lifestyle-related diseases. We examine evidence that near-infrared time-resolved spectroscopy (NIRTRS) is capable of estimating human BAT density (BAT-d). The parameters examined in this study are total hemoglobin [total-Hb]sup, oxygenated Hb [oxy-Hb]sup, deoxygenated Hb [deoxy-Hb]sup, Hb O2 saturation (StO2sup), and the reduced scattering coefficient in the supraclavicular region (μssup), where BAT deposits can be located; corresponding parameters in the control deltoid region are obtained as controls. Among the NIRTRS parameters, [total-Hb]sup and [oxy-Hb]sup show region-specific increases in winter, compared to summer. Further, [total-Hb]sup and [oxy-Hb]sup are correlated with cold-induced thermogenesis in the supraclavicular region. We conclude that NIRTRS-determined [total-Hb]sup and [oxy-Hb]sup are useful parameters for evaluating BAT-d in a simple, rapid, non-invasive manner. Full article
(This article belongs to the Special Issue Molecular Control of Adipose Cell Fate and Energy Metabolism)
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Review

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25 pages, 1126 KiB  
Review
The Beige Adipocyte as a Therapy for Metabolic Diseases
by Fernando Lizcano
Int. J. Mol. Sci. 2019, 20(20), 5058; https://doi.org/10.3390/ijms20205058 - 12 Oct 2019
Cited by 66 | Viewed by 8902
Abstract
Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown [...] Read more.
Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue more energetically active, with a greater number of mitochondria and energy production in the form of heat. Since adult humans possess significant amounts of active brown fat depots and its mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate themselves from white adipocytes. The presence of brown and beige adipocyte in human adults has acquired attention as a possible therapeutic intervention for metabolic diseases. Importantly, adult human brown appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as atherosclerosis, arterial hypertension and diabetes mellitus type 2. Because many epigenetics changes can affect beige adipocyte differentiation from adipose progenitor cells, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important to new pathways in the treatment of metabolic diseases. New molecules have emerged as possible therapeutic targets, which through the impulse to develop beige adipocytes can be useful for clinical studies. In this review will discuss some recent observations arising from the unique physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2. Full article
(This article belongs to the Special Issue Molecular Control of Adipose Cell Fate and Energy Metabolism)
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24 pages, 2241 KiB  
Review
Calcium Signaling Pathways: Key Pathways in the Regulation of Obesity
by Ziguo Song, Yu Wang, Fei Zhang, Fangyao Yao and Chao Sun
Int. J. Mol. Sci. 2019, 20(11), 2768; https://doi.org/10.3390/ijms20112768 - 5 Jun 2019
Cited by 43 | Viewed by 7272
Abstract
Nowadays, high epidemic obesity-triggered hypertension and diabetes seriously damage social public health. There is now a general consensus that the body’s fat content exceeding a certain threshold can lead to obesity. Calcium ion is one of the most abundant ions in the human [...] Read more.
Nowadays, high epidemic obesity-triggered hypertension and diabetes seriously damage social public health. There is now a general consensus that the body’s fat content exceeding a certain threshold can lead to obesity. Calcium ion is one of the most abundant ions in the human body. A large number of studies have shown that calcium signaling could play a major role in increasing energy consumption by enhancing the metabolism and the differentiation of adipocytes and reducing food intake through regulating neuronal excitability, thereby effectively decreasing the occurrence of obesity. In this paper, we review multiple calcium signaling pathways, including the IP3 (inositol 1,4,5-trisphosphate)-Ca2+ (calcium ion) pathway, the p38-MAPK (mitogen-activated protein kinase) pathway, and the calmodulin binding pathway, which are involved in biological clock, intestinal microbial activity, and nerve excitability to regulate food intake, metabolism, and differentiation of adipocytes in mammals, resulting in the improvement of obesity. Full article
(This article belongs to the Special Issue Molecular Control of Adipose Cell Fate and Energy Metabolism)
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