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Frontiers in Endocrinology 2023Thermogenic fat, consisting of brown and beige adipocytes, dissipates energy in the form of heat, in contrast to the characteristics of white adipocytes that store... (Review)
Review
Thermogenic fat, consisting of brown and beige adipocytes, dissipates energy in the form of heat, in contrast to the characteristics of white adipocytes that store energy. Increasing energy expenditure by activating brown adipocytes or inducing beige adipocytes is a potential therapeutic strategy for treating obesity and type 2 diabetes. Thus, a better understanding of the underlying mechanisms of thermogenesis provides novel therapeutic interventions for metabolic diseases. In this review, we summarize the recent advances in the molecular regulation of thermogenesis, focusing on transcription factors, epigenetic regulators, metabolites, and non-coding RNAs. We further discuss the intercellular and inter-organ crosstalk that regulate thermogenesis, considering the heterogeneity and complex tissue microenvironment of thermogenic fat.
Topics: Humans; Adipose Tissue, Brown; Diabetes Mellitus, Type 2; Adipocytes, Brown; Transcription Factors; Thermogenesis
PubMed: 37465124
DOI: 10.3389/fendo.2023.1215772 -
Molecules and Cells May 2023Obesity is a significant global health risk that can cause a range of serious metabolic problems, such as type 2 diabetes and cardiovascular diseases. Adipose tissue... (Review)
Review
Obesity is a significant global health risk that can cause a range of serious metabolic problems, such as type 2 diabetes and cardiovascular diseases. Adipose tissue plays a pivotal role in regulating energy and lipid storage. New research has underlined the crucial role of splicing factors in the physiological and functional regulation of adipose tissue. By generating multiple transcripts from a single gene, alternative splicing allows for a greater diversity of the proteome and transcriptome, which subsequently influence adipocyte development and metabolism. In this review, we provide an outlook on the part of splicing factors in adipogenesis and thermogenesis, and investigate how the different spliced isoforms can affect the development and function of adipose tissue.
Topics: Humans; Adipogenesis; Diabetes Mellitus, Type 2; RNA Splicing Factors; Adipose Tissue; Thermogenesis
PubMed: 37170770
DOI: 10.14348/molcells.2023.2195 -
Trends in Immunology Sep 2022Research focusing on adipose immunometabolism has been expanded from inflammation in white fat during obesity development to immune cell function regulating thermogenic... (Review)
Review
Research focusing on adipose immunometabolism has been expanded from inflammation in white fat during obesity development to immune cell function regulating thermogenic fat, energy expenditure, and systemic metabolism. This opinion discusses our current understanding of how resident immune cells within the thermogenic fat niche may regulate whole-body energy homeostasis. Furthermore, various types of immune cells can synthesize acetylcholine (ACh) and regulate important physiological functions. We highlight a unique subset of cholinergic macrophages within subcutaneous adipose tissue, termed cholinergic adipose macrophages (ChAMs); these macrophages interact with beige adipocytes through cholinergic receptor nicotinic alpha 2 subunit (CHRNA2) signaling to induce adaptive thermogenesis. We posit that these newly identified thermoregulatory macrophages may broaden our view of immune system functions for maintaining metabolic homeostasis and potentially treating obesity and metabolic disorders.
Topics: Adipocytes, Beige; Adipose Tissue; Cholinergic Agents; Humans; Obesity; Thermogenesis
PubMed: 35931611
DOI: 10.1016/j.it.2022.07.006 -
Trends in Endocrinology and Metabolism:... Apr 2014Brown adipose tissue (BAT) dissipates energy as heat to maintain optimal thermogenesis and to contribute to energy expenditure in rodents and possibly humans. The... (Review)
Review
Brown adipose tissue (BAT) dissipates energy as heat to maintain optimal thermogenesis and to contribute to energy expenditure in rodents and possibly humans. The energetic processes executed by BAT require a readily-available fuel supply, which includes glucose and fatty acids (FAs). FAs become available by cellular uptake, de novo lipogenesis, and multilocular lipid droplets in brown adipocytes. BAT also possesses a great capacity for glucose uptake and metabolism, and an ability to regulate insulin sensitivity. These properties make BAT an appealing target for the treatment of obesity, diabetes, and other metabolic disorders. Recent research has provided a better understanding of the processes of fuel utilization carried out by brown adipocytes, which is the focus of the current review.
Topics: Adipose Tissue, Brown; Animals; Energy Metabolism; Glucose; Humans; Lipid Metabolism; Thermogenesis
PubMed: 24389130
DOI: 10.1016/j.tem.2013.12.004 -
Signal Transduction and Targeted Therapy Sep 2022The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide and increased gradually. Most of them are... (Review)
Review
The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide and increased gradually. Most of them are listed on the table of high-risk factors for malignancy, and metabolic disorders systematically or locally contribute to cancer progression and poor prognosis of patients. Importantly, adipose tissue is fundamental to the occurrence and development of these metabolic disorders. White adipose tissue stores excessive energy, while thermogenic fat including brown and beige adipose tissue dissipates energy to generate heat. In addition to thermogenesis, beige and brown adipocytes also function as dynamic secretory cells and a metabolic sink of nutrients, like glucose, fatty acids, and amino acids. Accordingly, strategies that activate and expand thermogenic adipose tissue offer therapeutic promise to combat overweight, diabetes, and other metabolic disorders through increasing energy expenditure and enhancing glucose tolerance. With a better understanding of its origins and biological functions and the advances in imaging techniques detecting thermogenesis, the roles of thermogenic adipose tissue in tumors have been revealed gradually. On the one hand, enhanced browning of subcutaneous fatty tissue results in weight loss and cancer-associated cachexia. On the other hand, locally activated thermogenic adipocytes in the tumor microenvironment accelerate cancer progression by offering fuel sources and is likely to develop resistance to chemotherapy. Here, we enumerate current knowledge about the significant advances made in the origin and physiological functions of thermogenic fat. In addition, we discuss the multiple roles of thermogenic adipocytes in different tumors. Ultimately, we summarize imaging technologies for identifying thermogenic adipose tissue and pharmacologic agents via modulating thermogenesis in preclinical experiments and clinical trials.
Topics: Adipose Tissue, Brown; Amino Acids; Diabetes Mellitus, Type 2; Fatty Acids; Glucose; Humans; Metabolic Diseases; Neoplasms; Thermogenesis; Tumor Microenvironment
PubMed: 36114195
DOI: 10.1038/s41392-022-01178-6 -
Frontiers in Endocrinology 2020Exercise training results in beneficial adaptations to numerous tissues and offers protection against metabolic disorders including obesity and type 2 diabetes. Multiple... (Review)
Review
Exercise training results in beneficial adaptations to numerous tissues and offers protection against metabolic disorders including obesity and type 2 diabetes. Multiple studies have indicated that both white (WAT) and brown (BAT) adipose tissue may play an important role to mediate the beneficial effects of exercise. Studies from both rodents and humans have identified exercise-induced changes in WAT including increased mitochondrial activity and glucose uptake, an altered endocrine profile, and in rodents, a beiging of the WAT. Studies investigating the effects of exercise on BAT have resulted in conflicting data in terms of mitochondrial activity, glucose uptake, and thermogenic activity in rodents and humans, and remain an important area of investigation. This review discusses the exercise-induced adaptations to white and brown adipose tissue, distinguishing important differences between rodents and humans and highlighting the latest studies in the field and their implications.
Topics: Adaptation, Physiological; Adipose Tissue; Exercise; Humans; Thermogenesis
PubMed: 32411099
DOI: 10.3389/fendo.2020.00270 -
Nature Communications Jul 2022β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity...
β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. We have used pharmacological inhibitors and a direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in cultured brown adipocytes. Here we show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, however, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on transcription and function of cultured brown adipocytes.
Topics: Adipocytes, Brown; Adipose Tissue, Brown; Adrenergic Agents; Lipolysis; Peroxisome Proliferator-Activated Receptors; Thermogenesis
PubMed: 35803907
DOI: 10.1038/s41467-022-31525-8 -
International Journal of Molecular... Sep 2018Obesity is a health problem worldwide, and energy imbalance has been pointed out as one of the main factors responsible for its development. As mitochondria are a key... (Review)
Review
Obesity is a health problem worldwide, and energy imbalance has been pointed out as one of the main factors responsible for its development. As mitochondria are a key element in energy homeostasis, the development of obesity has been strongly associated with mitochondrial imbalance. Polyphenols are the largest group of phytochemicals, widely distributed in the plant kingdom, abundant in fruits and vegetables, and have been classically described as antioxidants owing to their well-established ability to eliminate free radicals and reactive oxygen species (ROS). During the last decade, however, growing evidence reports the ability of polyphenols to perform several important biological activities in addition to their antioxidant activity. Special attention has been given to the ability of polyphenols to modulate mitochondrial processes. Thus, some polyphenols are now recognized as molecules capable of modulating pathways that regulate mitochondrial biogenesis, ATP synthesis, and thermogenesis, among others. The present review reports the main benefits of polyphenols in modulating mitochondrial processes that favor the regulation of energy expenditure and offer benefits in the management of obesity, especially thermogenesis and mitochondrial biogenesis.
Topics: Animals; Humans; Immunity, Innate; Microarray Analysis; Mitochondria; Organelle Biogenesis; Polyphenols; Reactive Oxygen Species; Thermogenesis
PubMed: 30217101
DOI: 10.3390/ijms19092757 -
Trends in Endocrinology and Metabolism:... Oct 2019The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy... (Review)
Review
The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy expenditure represents one such approach. Brown adipocytes and the related beige adipocytes oxidize fatty acids and glucose to generate heat and are activated by cold exposure or consumption of high-calorie diets. Alternative, more practical means to activate thermogenic fat are needed. Here, we review emerging data suggesting new roles for lipids in activating thermogenesis that extend beyond their serving as a fuel source for heat generation. Lipids have also been implicated in mediating interorgan communication, crosstalk between organelles, and cellular signaling regulating thermogenesis. Understanding how lipids regulate thermogenesis could identify innovative therapeutic interventions for obesity.
Topics: Adipose Tissue, Beige; Animals; Humans; Mitochondria; Obesity; Plasmalogens; Thermogenesis
PubMed: 31422871
DOI: 10.1016/j.tem.2019.07.020 -
Cellular & Molecular Immunology Mar 2022Glucose is a vital source of energy for all mammals. The balance between glucose uptake, metabolism and storage determines the energy status of an individual, and... (Review)
Review
Glucose is a vital source of energy for all mammals. The balance between glucose uptake, metabolism and storage determines the energy status of an individual, and perturbations in this balance can lead to metabolic diseases. The maintenance of organismal glucose metabolism is a complex process that involves multiple tissues, including adipose tissue, which is an endocrine and energy storage organ that is critical for the regulation of systemic metabolism. Adipose tissue consists of an array of different cell types, including specialized adipocytes and stromal and endothelial cells. In addition, adipose tissue harbors a wide range of immune cells that play vital roles in adipose tissue homeostasis and function. These cells contribute to the regulation of systemic metabolism by modulating the inflammatory tone of adipose tissue, which is directly linked to insulin sensitivity and signaling. Furthermore, these cells affect the control of thermogenesis. While lean adipose tissue is rich in type 2 and anti-inflammatory cytokines such as IL-10, obesity tips the balance in favor of a proinflammatory milieu, leading to the development of insulin resistance and the dysregulation of systemic metabolism. Notably, anti-inflammatory immune cells, including regulatory T cells and innate lymphocytes, protect against insulin resistance and have the characteristics of tissue-resident cells, while proinflammatory immune cells are recruited from the circulation to obese adipose tissue. Here, we review the key findings that have shaped our understanding of how immune cells regulate adipose tissue homeostasis to control organismal metabolism.
Topics: Adipocytes; Adipose Tissue; Animals; Endothelial Cells; Energy Metabolism; Insulin Resistance; Mammals; Thermogenesis
PubMed: 34837070
DOI: 10.1038/s41423-021-00804-7