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International Journal of Molecular... Oct 2019Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the... (Review)
Review
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.
Topics: Adipocytes, Beige; Animals; Anti-Obesity Agents; Exercise; Humans; Metabolic Diseases; Thermogenesis
PubMed: 31614705
DOI: 10.3390/ijms20205058 -
PloS One 2022We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The...
We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The order and effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adipocyte differentiation and evaluated the effect of the regulators on gene expression in terms of direction and magnitude. Then, we identified the overlap of the transcription factors and co-factors binding sites and targets. Finally, we built a chromatin state model based on the histone marks and studied their relation to the factors' binding. Adipogenic factors differentially regulated autophagy genes as part of the differentiation program. Co-regulators associated with specific transcription factors and preceded them to the regulatory regions. Transcription factors differed in the binding time and location, and their effect on expression was either localized or long-lasting. Adipogenic factors disproportionately targeted genes coding for autophagy-specific transcription factors. In sum, a hierarchical arrangement between adipogenic transcription factors and co-factors drives the regulation of autophagy during adipocyte differentiation.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Autophagy; Cell Differentiation; Cell Line; Computational Biology; Gene Expression Regulation; Mice
PubMed: 35081114
DOI: 10.1371/journal.pone.0250865 -
Adipocyte Dec 2020As an important second messenger in adipocytes, calcium ions (Ca) are essential in regulating various intracellular signalling pathways that control critical cellular... (Review)
Review
As an important second messenger in adipocytes, calcium ions (Ca) are essential in regulating various intracellular signalling pathways that control critical cellular functions. Calcium channels show selective permeability to Ca and facilitate Ca entry into the cytoplasm, which are normally located in the plasmatic and intracellular membranes. The increase of cytosolic Ca modulates a variety of signalling pathways and results in the transcription of target genes that contribute to adipogenesis, a key cellular event includes proliferation and differentiation of adipocyte. In the past decades, the involvement of some Ca-permeable ion channels, such as Ca release-activated Ca channels, transient receptor potential channels, voltage-gated calcium channels and others, in adipogenesis has been extensively explored. In the present review, we provided a summary of the expression and contributions of these Ca-permeable channels in mediating Ca influxes that drive adipogenesis. Moreover, we discussed their potentials as future therapeutic targets.
Topics: Adipocytes; Adipogenesis; Animals; Calcium; Calcium Channels; Humans
PubMed: 32175809
DOI: 10.1080/21623945.2020.1738792 -
Cells Feb 2020It is well established that breast cancer development and progression depend not only on tumor-cell intrinsic factors but also on its microenvironment and on the host... (Review)
Review
It is well established that breast cancer development and progression depend not only on tumor-cell intrinsic factors but also on its microenvironment and on the host characteristics. There is growing evidence that adipocytes play a role in breast cancer progression. This is supported by: i) epidemiological studies reporting the association of obesity with a higher cancer risk and poor prognosis, ii) recent studies demonstrating the existence of a cross-talk between breast cancer cells and adipocytes locally in the breast that leads to acquisition of an aggressive tumor phenotype, and iii) evidence showing that cancer cachexia applies also to fat tissue and shares similarities with stromal-carcinoma metabolic synergy. This review summarizes the current knowledge on the epidemiological link between obesity and breast cancer and outlines the results of the tumor-adipocyte crosstalk. We also focus on systemic changes in body fat in patients with cachexia developed in the course of cancer. Moreover, we discuss and compare adipocyte alterations in the three pathological conditions and the mechanisms through which breast cancer progression is induced.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Breast Neoplasms; Carcinogenesis; Female; Humans; Obesity
PubMed: 32120856
DOI: 10.3390/cells9030560 -
International Journal of Molecular... Aug 2021It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central... (Review)
Review
It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to "safely" store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.
Topics: Adipocytes; Adipose Tissue; Homeostasis; Insulin Resistance; Lipid Metabolism; Peroxisome Proliferator-Activated Receptors
PubMed: 34445679
DOI: 10.3390/ijms22168974 -
Cells Dec 2020For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among... (Review)
Review
For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.
Topics: Adipocytes; Adipocytes, Brown; Adipocytes, White; Adipogenesis; Animals; Carcinogenesis; Cell Differentiation; Homeostasis; Humans; Lipid Metabolism; Tumor Suppressor Protein p53
PubMed: 33297294
DOI: 10.3390/cells9122621 -
Adipocyte Dec 2019Individual cell types vary enormously in the amount of different organelles they contain. One such organelle is the mitochondrion. Understanding how mitochondrial levels... (Review)
Review
Individual cell types vary enormously in the amount of different organelles they contain. One such organelle is the mitochondrion. Understanding how mitochondrial levels are controlled is essential since so many disease states seem to involve mitochondrial function. The beige adipocyte is an inducible form of adipocyte that emerges in response to cold exposure and some other external stimuli. To perform its thermogenic function, its level of mitochondria increases dramatically. If the stimuli are removed the mitochondrial levels return to base line. Following the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through mitophagy-mediated mitochondrial degradation. The beige cell is therefore a dynamic model for studying the mechanism of mitochondrial biogenesis and degradation.
Topics: Adipocytes; Adipocytes, Beige; Adipose Tissue, Beige; Adipose Tissue, White; Animals; Humans; Mitochondria; Mitophagy; Organelle Biogenesis; Phenotype; Signal Transduction; Thermogenesis; Uncoupling Protein 1
PubMed: 30686106
DOI: 10.1080/21623945.2019.1574194 -
Cell Reports. Medicine Jan 2024The discovery of exercise-regulated circulatory factors has fueled interest in organ crosstalk, especially between skeletal muscle and adipose tissue, and the role in...
The discovery of exercise-regulated circulatory factors has fueled interest in organ crosstalk, especially between skeletal muscle and adipose tissue, and the role in mediating beneficial effects of exercise. We studied the adipose tissue transcriptome in men and women with normal glucose tolerance or type 2 diabetes following an acute exercise bout, revealing substantial exercise- and time-dependent changes, with sustained increase in inflammatory genes in type 2 diabetes. We identify oncostatin-M as one of the most upregulated adipose-tissue-secreted factors post-exercise. In cultured human adipocytes, oncostatin-M enhances MAPK signaling and regulates lipolysis. Oncostatin-M expression arises predominantly from adipose tissue immune cell fractions, while the corresponding receptors are expressed in adipocytes. Oncostatin-M expression increases in cultured human Thp1 macrophages following exercise-like stimuli. Our results suggest that immune cells, via secreted factors such as oncostatin-M, mediate a crosstalk between skeletal muscle and adipose tissue during exercise to regulate adipocyte metabolism and adaptation.
Topics: Female; Humans; Male; Adipocytes; Adipose Tissue; Cells, Cultured; Diabetes Mellitus, Type 2; Lipolysis
PubMed: 38151020
DOI: 10.1016/j.xcrm.2023.101348 -
Cell Metabolism May 2022Adipose tissue (AT) plays a central role in systemic metabolic homeostasis, but its function during bacterial infection remains unclear. Following subcutaneous bacterial...
Adipose tissue (AT) plays a central role in systemic metabolic homeostasis, but its function during bacterial infection remains unclear. Following subcutaneous bacterial infection, adipocytes surrounding draining lymph nodes initiated a transcriptional response indicative of stimulation with IFN-γ and a shift away from lipid metabolism toward an immunologic function. Natural killer (NK) and invariant NK T (iNKT) cells were identified as sources of infection-induced IFN-γ in perinodal AT (PAT). IFN-γ induced Nos2 expression in adipocytes through a process dependent on nuclear-binding oligomerization domain 1 (NOD1) sensing of live intracellular bacteria. iNOS expression was coupled to metabolic rewiring, inducing increased diversion of extracellular L-arginine through the arginosuccinate shunt and urea cycle to produce nitric oxide (NO), directly mediating bacterial clearance. In vivo, control of infection in adipocytes was dependent on adipocyte-intrinsic sensing of IFN-γ and expression of iNOS. Thus, adipocytes are licensed by innate lymphocytes to acquire anti-bacterial functions during infection.
Topics: Adipocytes; Cues; Immunity; Interferon-gamma; Killer Cells, Natural
PubMed: 35508110
DOI: 10.1016/j.cmet.2022.04.008 -
Mucosal Immunology Nov 2021Epidemiological evidence establishes obesity as an independent risk factor for increased susceptibility and severity to viral respiratory pneumonias associated with H1N1... (Review)
Review
Epidemiological evidence establishes obesity as an independent risk factor for increased susceptibility and severity to viral respiratory pneumonias associated with H1N1 influenza and SARS-CoV-2 pandemics. Given the global obesity prevalence, a better understanding of the mechanisms behind obese susceptibility to infection is imperative. Altered immune cell metabolism and function are often perceived as a key causative factor of dysregulated inflammation. However, the contribution of adipocytes, the dominantly altered cell type in obesity with broad inflammatory properties, to infectious disease pathogenesis remains largely ignored. Thus, skewing of adipocyte-intrinsic cellular metabolism may lead to the development of pathogenic inflammatory adipocytes, which shape the overall immune responses by contributing to either premature immunosenescence, delayed hyperinflammation, or cytokine storm in infections. In this review, we discuss the underappreciated contribution of adipocyte cellular metabolism and adipocyte-produced mediators on immune system modulation and how such interplay may modify disease susceptibility and pathogenesis of influenza and SARS-CoV-2 infections in obese individuals.
Topics: Adipocytes; COVID-19; Humans; Inflammation; Influenza A Virus, H1N1 Subtype; Influenza, Human; SARS-CoV-2
PubMed: 33958704
DOI: 10.1038/s41385-021-00404-8