scholarly journals Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

2019 ◽  
Author(s):  
Devjanee Swain-Lenz ◽  
Alejandro Berrio ◽  
Alexias Safi ◽  
Gregory E. Crawford ◽  
Gregory A. Wray

AbstractHumans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using macaque as an outgroup. We find that many cis-regulatory regions that are specifically closed in humans are under positive selection, located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which white adipocytes are transdifferentiated into beige adipocytes. While the primary role of white adipocytes is to store lipids, beige adipocytes are thermogeneic. The collective closing of many putative regulatory regions associated with beiging of fat suggests an adaptive mechanism that increases body fat in humans.

2019 ◽  
Vol 11 (7) ◽  
pp. 1997-2008 ◽  
Author(s):  
Devjanee Swain-Lenz ◽  
Alejandro Berrio ◽  
Alexias Safi ◽  
Gregory E Crawford ◽  
Gregory A Wray

AbstractHumans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using rhesus macaque as an outgroup. We find that many regions that have decreased accessibility in humans are enriched for promoter and enhancer sequences, are depleted for signatures of negative selection, are located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which lipid-storing white adipocytes are transdifferentiated into thermogenic beige adipocytes. The collective closing of many putative regulatory regions associated with beigeing of fat suggests a mechanism that increases body fat in humans.


Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 23 ◽  
Author(s):  
Quyen Luong ◽  
Jun Huang ◽  
Kevin Y. Lee

Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies.


Author(s):  
Aung Than ◽  
Shaohai Xu ◽  
Ru Li ◽  
MelvinKhee-Shing Leow ◽  
Lei Sun ◽  
...  

Abstract Brown adipose tissue dissipates energy in the form of heat. Recent studies have shown that adult humans possess both classical brown and beige adipocytes (brown-like adipocytes in white adipose tissue, WAT), and stimulating brown and beige adipocyte formation can be a new avenue to treat obesity. Angiotensin II (AngII) is a peptide hormone that plays important roles in energy metabolism via its angiotensin type 1 or type 2 receptors (AT1R and AT2R). Adipose tissue is a major source of AngII and expresses both types of its receptors, implying the autocrine and paracrine role of AngII in regulating adipose functions and self-remodeling. Here, based on the in vitro studies on primary cultures of mouse white adipocytes, we report that, AT2R activation, either by AngII or AT2R agonist (C21), induces white adipocyte browning, by increasing PPARγ expression, at least in part, via ERK1/2, PI3kinase/Akt and AMPK signaling pathways. It is also found that AngII–AT2R enhances brown adipogenesis. In the in vivo studies on mice, administration of AT1R antagonist (ZD7155) or AT2R agonist (C21) leads to the increase of WAT browning, body temperature and serum adiponectin, as well as the decrease of WAT mass and the serum levels of TNFα, triglycerides and free fatty acids. In addition, AT2R-induced browning effect is also observed in human white adipocytes, as evidenced by the increased UCP1 expression and oxygen consumption. Finally, we provide evidence that AT2R plays important roles in hormone T3-induced white adipose browning. This study, for the first time, reveals the browning and brown adipogenic effects of AT2R and suggests a potential therapeutic target to combat obesity and related metabolic disorders.


Author(s):  
Alev Eroglu Altinova

Abstract Beige adipocyte, the third and relatively new type of adipocyte, can emerge in white adipose tissue (WAT) under thermogenic stimulations that is termed as browning of WAT. Recent studies suggest that browning of WAT deserves more attention and therapies targeting browning of WAT can be helpful for reducing obesity. Beyond the major inducers of browning, namely cold and β3-adrenergic stimulation, beige adipocytes are affected by several factors, and excess adiposity per se may also influence the browning process. The objective of the present review is to provide an overview of recent clinical and preclinical studies on the hormonal and non-hormonal factors that affect the browning of WAT. This review further focuses on the role of obesity per se on browning process.


2022 ◽  
Vol 127 (2) ◽  
pp. 161-164
Author(s):  
Paul Trayhurn

I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ.


Author(s):  
Jiamiao Hu ◽  
Mark Christian

AbstractAdipose tissue has been historically classified into anabolic white adipose tissue (WAT) and catabolic brown adipose tissue (BAT). Recent studies have revealed the plasticity of WAT, where white adipocytes can be induced into ‘brown-like’ heat-producing adipocytes (BRITE or beige adipocytes). Recruiting and activating BRITE adipocytes in WAT (so-called ‘browning’) is believed to provide new avenues for the treatment of obesity-related diseases. A number of hormonal factors have been found to regulate BRITE adipose development and activity through autocrine, paracrine and systemic mechanisms. In this mini-review we will discuss the impact of these factors on the browning process, especially those hormonal factors identified with direct effects on white adipocytes.


2021 ◽  
pp. 153537022110060
Author(s):  
Yue Chen ◽  
Jie Ding ◽  
Yufei Zhao ◽  
Shenghong Ju ◽  
Hui Mao ◽  
...  

This study aimed to track and evaluate the effect of low-dose irisin on the browning of white adipose tissue (WAT) in mice using magnetic resonance imaging (MRI) noninvasively in vivo. Mature white adipocytes extracted from mice were cultured, induced and characterized before being treated by irisin. The volume and fat fraction of WAT were quantified using MRI in normal chow diet and high fat mice after injection of irisin. The browning of cultured white adipocytes and WAT in mice were validated by immunohistochemistry and western blotting for uncoupling protein 1 (UCP1) and deiodinase type II (DIO2). The serum indexes were examined with high fat diet after irisin intervention. UCP1 and DIO2 in adipocytes showed increases responding to the irisin treatment. The size of white adipocytes in mice receiving irisin intervention was reduced. MRI measured volumes and fat fraction of WAT were significantly lower after Irisin treatment. Blood glucose and cholesterol levels were reduced in high fat diet mice after irisin treatment. Irisin intervention exerted browning of WAT, resulting reduction of volume and fat fraction of WAT as measured by MRI. Furthermore, it improved the condition of mice with diet-induced obesity and related metabolic disorders.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasia Georgiadi ◽  
Valeria Lopez-Salazar ◽  
Rabih El- Merahbi ◽  
Rhoda Anane Karikari ◽  
Xiaochuan Ma ◽  
...  

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.


2021 ◽  
Vol 22 (11) ◽  
pp. 5560
Author(s):  
Alejandro Álvarez-Artime ◽  
Belén García-Soler ◽  
Rosa María Sainz ◽  
Juan Carlos Mayo

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.


2021 ◽  
Vol 22 (11) ◽  
pp. 6025
Author(s):  
Masaki Kobayashi ◽  
Yusuke Deguchi ◽  
Yuka Nozaki ◽  
Yoshikazu Higami

Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) regulates mitochondrial DNA replication and mitochondrial gene expression by interacting with several transcription factors. White adipose tissue (WAT) mainly comprises adipocytes that store triglycerides as an energy resource and secrete adipokines. The characteristics of WAT vary in response to systemic and chronic metabolic alterations, including obesity or caloric restriction. Despite a small amount of mitochondria in white adipocytes, accumulated evidence suggests that mitochondria are strongly related to adipocyte-specific functions, such as adipogenesis and lipogenesis, as well as oxidative metabolism for energy supply. Therefore, PGC-1α is expected to play an important role in WAT. In this review, we provide an overview of the involvement of mitochondria and PGC-1α with obesity- and caloric restriction-related physiological changes in adipocytes and WAT.


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