scholarly journals Adipocyte dedifferentiation in health and diseases

2019 ◽  
Vol 133 (20) ◽  
pp. 2107-2119 ◽  
Author(s):  
Tongxing Song ◽  
Shihuan Kuang
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
De Novo ◽  
Adipocyte Size ◽  
Cell Type ◽  
Mature Adipocyte ◽  
Endocrine Organ ◽  
Pathological Conditions ◽  
Major Cell Type ◽  
Local Metabolism

Abstract Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedifferentiation, whereby a mature adipocyte is reverted to an undifferentiated progenitor-like status, has been reported as a mechanism underlying adipocyte plasticity. Dedifferentiation of mature adipocytes has been observed under both physiological and pathological conditions. This review covers several aspects of adipocyte dedifferentiation, its relevance to adipose tissue function, molecular pathways that drive dedifferentiation, and the potential of therapeutic targeting adipocyte dedifferentiation in human health and metabolic diseases.

The origin of intermuscular adipose tissue and its pathophysiological implications

2009 ◽  
Vol 297 (5) ◽  
pp. E987-E998 ◽  
Author(s):  
Roberto Vettor ◽  
Gabriella Milan ◽  
Chiara Franzin ◽  
Marta Sanna ◽  
Paolo De Coppi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
High Plasma ◽  
Stem Cell Population ◽  
Phenotypic Switch ◽  
Mesenchymal Progenitors ◽  
Intermuscular Adipose Tissue ◽  
Pathological Conditions ◽  
Age Related ◽  
Mitochondrial Ros

The intermuscular adipose tissue (IMAT) is a depot of adipocytes located between muscle bundles. Several investigations have recently been carried out to define the phenotype, the functional characteristics, and the origin of the adipocytes present in this depot. Among the different mechanisms that could be responsible for the accumulation of fat in this site, the dysdifferentiation of muscle-derived stem cells or other mesenchymal progenitors has been postulated, turning them into cells with an adipocyte phenotype. In particular, muscle satellite cells (SCs), a heterogeneous stem cell population characterized by plasticity and self-renewal that allow muscular growth and regeneration, can acquire features of adipocytes, including the abilities to express adipocyte-specific genes and accumulate lipids. Failure to express the transcription factors that direct mesenchymal precursors into fully differentiated functionally specialized cells may be responsible for their phenotypic switch into the adipogenic lineage. We proved that human SCs also possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle. This occurs under some pathological conditions (i.e., primary myodystrophies, obesity, hyperglycemia, high plasma free fatty acids, hypoxia, etc.) or as a consequence of thiazolidinedione treatment or simply because of a sedentary lifestyle or during aging. Several pathways and factors (PPARs, WNT growth factors, myokines, GEF-GAP-Rho, p66shc, mitochondrial ROS production, PKCβ) could be implicated in the adipogenic conversion of SCs. The understanding of the molecular pathways that regulate muscle-to-fat conversion and SC behavior could explain the increase in IMAT depots that characterize many metabolic diseases and age-related sarcopenia.

scholarly journals Right Heart Morphology and Its Association With Excessive and Deficient Cardiac Visceral Adipose Tissue

2021 ◽  
Vol 15 ◽  
pp. 117954682110413
Author(s):  
Domagoj Vučić ◽  
Nikola Bijelić ◽  
Edi Rođak ◽  
Jasmina Rajc ◽  
Boris Dumenčić ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Right Heart ◽  
Endocrine Organ ◽  
Mortality And Morbidity ◽  
Non Invasive ◽  
Pathological Conditions ◽  
Oncological Diseases ◽  
The Right ◽  
Visceral Adipose

Visceral adipose tissue is an independent risk factor for the development of atherosclerotic coronary disease, arterial hypertension, diabetes and metabolic syndrome. Right heart morphology often involves the presence of adipose tissue, which can be quantified by non-invasive imaging methods. The last decade brought a wealth of new insights into the function and morphology of adipose tissue, with great emphasis on its role in the pathogenesis of heart disease. Cardiac adipose tissue is involved in thermogenesis, mechanical protection of the heart and energy storage. However, it can also be an endocrine organ that synthesises numerous pro-inflammatory and anti-inflammatory cytokines, the effect of which is accomplished by paracrine and vasocrine mechanisms. Visceral adipose tissue has several compartments that differ in their embryological origin and vascularisation. Deficiency of cardiac adipose tissue, often due to chronic pathological conditions such as oncological diseases or chronic infectious diseases, predicts increased mortality and morbidity. To date, knowledge about the influence of visceral adipose tissue on cardiac morphology is limited, especially the effect on the morphology of the right heart in a state of excess or deficient visceral adipose tissue.

scholarly journals Pinch Loss Ameliorates Obesity, Glucose Intolerance and Fatty Liver by Modulating Adipocyte Apoptosis in Mice

2021 ◽  
Author(s):  
Huanqing Gao ◽  
Yiming Zhong ◽  
Zhen Ding ◽  
Sixiong Lin ◽  
Xiaoting Hou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Glucose Intolerance ◽  
Metabolic Diseases ◽  
Caspase 8 ◽  
Chow Diet ◽  
Adipocyte Size ◽  
Genetic Ablation ◽  
Brown Adipose

The mammalian focal adhesion proteins Pinch1/2 activate integrins and promote cell-ECM adhesion and migration; however, their roles in adipose tissue and metabolism are unclear. Here we find that high fat diet (HFD) feeding dramatically increases expression of Pinch1/2 proteins in white adipose tissues (WAT) in mice. Furthermore, expression of Pinch1 is largely up-regulated in WAT in the Leptin-deficient ob/ob type 2 diabetic mice and obese humans. While mice with the loss of Pinch1 in adipocytes or global Pinch2 do not display any notable phenotypes, deleting Pinch1 in adipocytes and Pinch2 globally significantly decreases body weight and WAT, but not brown adipose tissue (BAT), mass in HFD-, but not normal chow diet (NCD)-, fed mice. Pinch loss ameliorates HFD-induced glucose intolerance and fatty liver. After HFD challenge, Pinch loss slightly, but significantly, accelerates energy expenditure. While Pinch loss decreases adipocyte size and alters adipocyte size distribution, it greatly accelerates cell apoptosis primarily in epididymal WAT and to a less extent subcutaneous WAT. In vitro studies demonstrate that Pinch loss accelerates adipocyte apoptosis by activating the Bim/Caspase-8 pathway. In vivo, genetic ablation of Caspase-8 expression in adipocytes essentially abolishes the ameliorating effects of Pinch deficiency on obesity, glucose intolerance and fatty liver in mice. Thus, we demonstrate a previously unknown function of Pinch in control of adipose mass, glucose and fat metabolism via modulation of adipocyte apoptosis. We may define a novel target for the prevention and treatment of metabolic diseases, such as obesity and diabetics.

scholarly journals Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laura Pajed ◽  
Ulrike Taschler ◽  
Anna Tilp ◽  
Peter Hofer ◽  
Petra Kotzbeck ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
De Novo ◽  
Lipolytic Activity ◽  
De Novo Lipogenesis ◽  
Hormone Sensitive Lipase ◽  
Hepatic Lipid Accumulation ◽  
Hormone Sensitive

AbstractModulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.

scholarly journals Endurance Exercise Mitigates Immunometabolic Adipose Tissue Disturbances in Cancer and Obesity

2020 ◽  
Vol 21 (24) ◽  
pp. 9745
Author(s):  
José Cesar Rosa-Neto ◽  
Loreana Sanches Silveira
Keyword(s):  
Adipose Tissue ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Aerobic Exercise Training ◽  
Endocrine Organ ◽  
Important Field ◽  
Obesity And Cancer

Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation by adipocytokines secretion. The interactions between metabolic active tissues and immune cells, called immunometabolism, is an important field for discovering new pathways and approaches to treat immunometabolic diseases, such as obesity and cancer. Moreover, physical exercise is widely known as a tool for prevention and adjuvant treatment on metabolic diseases. More specifically, aerobic exercise training is able to increase the energy expenditure, reduce the nutrition overload and modify the profile of adipocytokines and myokines with paracrine and endocrine effects. Therefore, our aim in this review was to cover the effects of aerobic exercise training on the immunometabolism of adipose tissue in obesity and cancer, focusing on the exercise-related modification on adipose tissue or immune cells isolated as well as their interaction.

scholarly journals Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2163
Author(s):  
Yetirajam Rajesh ◽  
Devanand Sarkar
Keyword(s):  
Adipose Tissue ◽  
Cancer Progression ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Metabolic Complications ◽  
Endocrine Organ ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms ◽  
Low Grade Inflammation ◽  
Excessive Accumulation

Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC.

scholarly journals Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2′,4,4′-Tetrabromodiphenyl Ether (BDE-47)

2018 ◽  
Author(s):  
Aser Abrha ◽  
Alexander Suvorov
Keyword(s):  
Adipose Tissue ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Metabolic Diseases ◽  
De Novo ◽  
Coagulation Factors ◽  
Bioinformatic Analysis ◽  
De Novo Lipogenesis ◽  
Target Tissue ◽  
Pregnant Mice

For the majority of lipophilic compounds adipose tissue is traditionally considered as storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposures may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) is a group of lipophilic flame retardants found in majority of human samples in North America. Their ability to alter physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using RNA-seq approach with subsequent bioinformatic analysis. Genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism were altered in expression in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.

scholarly journals Dim Light at Night Disturbs Molecular Pathways of Lipid Metabolism

2020 ◽  
Vol 21 (18) ◽  
pp. 6919
Author(s):  
Monika Okuliarova ◽  
Valentina Sophia Rumanova ◽  
Katarina Stebelova ◽  
Michal Zeman
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
De Novo ◽  
Negative Impact ◽  
Acid Uptake ◽  
Control Mechanisms ◽  
Light At Night ◽  
Dim Light

Dim light at night (dLAN) is associated with metabolic risk but the specific effects on lipid metabolism have only been evaluated to a limited extent. Therefore, to explore whether dLAN can compromise lipid metabolic homeostasis in healthy individuals, we exposed Wistar rats to dLAN (~2 lx) for 2 and 5 weeks and analyzed the main lipogenic pathways in the liver and epididymal fat pad, including the control mechanisms at the hormonal and molecular level. We found that dLAN promoted hepatic triacylglycerol accumulation, upregulated hepatic genes involved in de novo synthesis of fatty acids, and elevated glucose and fatty acid uptake. These observations were paralleled with suppressed fatty acid synthesis in the adipose tissue and altered plasma adipokine levels, indicating disturbed adipocyte metabolic function with a potential negative impact on liver metabolism. Moreover, dLAN-exposed rats displayed an elevated expression of two peroxisome proliferator-activated receptor family members (Pparα and Pparγ) in the liver and adipose tissue, suggesting the deregulation of important metabolic transcription factors. Together, our results demonstrate that an impaired balance of lipid biosynthetic pathways caused by dLAN can increase lipid storage in the liver, thereby accounting for a potential linking mechanism between dLAN and metabolic diseases.

scholarly journals Adipocytokines in obesity and metabolic disease

2014 ◽  
Vol 220 (2) ◽  
pp. T47-T59 ◽  
Author(s):  
Haiming Cao
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Clinical Settings ◽  
Low Grade ◽  
Endocrine Organ ◽  
Metabolic Inflammation ◽  
The Past ◽  
Wide Range ◽  
Low Grade Inflammation

The current global obesity pandemic is the leading cause for the soaring rates of metabolic diseases, especially diabetes, cardiovascular disease, hypertension, and non-alcoholic hepatosteatosis. Efforts devoted to find cures for obesity and associated disorders in the past two decades have prompted intensive interest in adipocyte biology, and have led to major advances in the mechanistic understanding of adipose tissue as an essential endocrine organ. Adipose tissue secretes an array of hormones (adipokines) that signal key organs to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. In addition, obesity induces production of inflammatory cytokines (often referred to together with adipokines as adipocytokines) and infiltration of immune cells into adipose tissue, which creates a state of chronic low-grade inflammation. Metabolic inflammation has been increasingly recognized as a unifying mechanism linking obesity to a broad spectrum of pathological conditions. This review focuses on classic examples of adipocytokines that have helped to form the basis of the endocrine and inflammatory roles of adipose tissue, and it also details a few newly characterized adipocytokines that provide fresh insights into adipose biology. Studies of adipocytokines in clinical settings and their therapeutic potential are also discussed.

scholarly journals Pinch Loss Ameliorates Obesity, Glucose Intolerance and Fatty Liver by Modulating Adipocyte Apoptosis in Mice

2021 ◽  
Author(s):  
Huanqing Gao ◽  
Yiming Zhong ◽  
Zhen Ding ◽  
Sixiong Lin ◽  
Xiaoting Hou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Glucose Intolerance ◽  
Metabolic Diseases ◽  
Caspase 8 ◽  
Chow Diet ◽  
Adipocyte Size ◽  
Genetic Ablation ◽  
Brown Adipose

The mammalian focal adhesion proteins Pinch1/2 activate integrins and promote cell-ECM adhesion and migration; however, their roles in adipose tissue and metabolism are unclear. Here we find that high fat diet (HFD) feeding dramatically increases expression of Pinch1/2 proteins in white adipose tissues (WAT) in mice. Furthermore, expression of Pinch1 is largely up-regulated in WAT in the Leptin-deficient ob/ob type 2 diabetic mice and obese humans. While mice with the loss of Pinch1 in adipocytes or global Pinch2 do not display any notable phenotypes, deleting Pinch1 in adipocytes and Pinch2 globally significantly decreases body weight and WAT, but not brown adipose tissue (BAT), mass in HFD-, but not normal chow diet (NCD)-, fed mice. Pinch loss ameliorates HFD-induced glucose intolerance and fatty liver. After HFD challenge, Pinch loss slightly, but significantly, accelerates energy expenditure. While Pinch loss decreases adipocyte size and alters adipocyte size distribution, it greatly accelerates cell apoptosis primarily in epididymal WAT and to a less extent subcutaneous WAT. In vitro studies demonstrate that Pinch loss accelerates adipocyte apoptosis by activating the Bim/Caspase-8 pathway. In vivo, genetic ablation of Caspase-8 expression in adipocytes essentially abolishes the ameliorating effects of Pinch deficiency on obesity, glucose intolerance and fatty liver in mice. Thus, we demonstrate a previously unknown function of Pinch in control of adipose mass, glucose and fat metabolism via modulation of adipocyte apoptosis. We may define a novel target for the prevention and treatment of metabolic diseases, such as obesity and diabetics.

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