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International Journal of Environmental... Sep 2021Development of obesity is primarily the result of imbalance between energy intake and energy expenditure. Thyroid hormones influence energy expenditure by regulating... (Review)
Review
Development of obesity is primarily the result of imbalance between energy intake and energy expenditure. Thyroid hormones influence energy expenditure by regulating cellular respiration and thermogenesis and by determining resting metabolic rate. Triiodothyronine influences lipid turnover in adipocytes and impacts appetite regulation through the central nervous system, mainly the hypothalamus. Thyroid-stimulating hormone may also influence thermogenesis, suppress appetite and regulate lipid storage through lipolysis and lipogenesis control. Subclinical hypothyroidism may induce changes in basal metabolic rate with subsequent increase in BMI, but obesity can also affect thyroid function via several mechanisms such as lipotoxicity and changes in adipokines and inflammatory cytokine secretion. The present study investigated the complex and mutual relationships between the thyroid axis and adiposity.
Topics: Basal Metabolism; Energy Metabolism; Humans; Obesity; Thermogenesis; Thyroid Gland
PubMed: 34574358
DOI: 10.3390/ijerph18189434 -
Cell Metabolism Jan 2019Brown and beige adipocytes can catabolize stored energy to generate heat, and this distinct capacity for thermogenesis could be leveraged as a therapy for metabolic... (Review)
Review
Brown and beige adipocytes can catabolize stored energy to generate heat, and this distinct capacity for thermogenesis could be leveraged as a therapy for metabolic diseases like obesity and type 2 diabetes. Thermogenic adipocytes drive heat production through close coordination of substrate supply with the mitochondrial oxidative machinery and effectors that control the rate of substrate oxidation. Together, this apparatus affords these adipocytes with tremendous capacity to drive thermogenesis. The best characterized thermogenic effector is uncoupling protein 1 (UCP1). Importantly, additional mechanisms for activating thermogenesis beyond UCP1 have been identified and characterized to varying extents. Acute regulation of these thermogenic pathways has been an active area of study, and numerous regulatory factors have been uncovered in recent years. Here we will review the evidence for regulators of heat production in thermogenic adipocytes in the context of the thermodynamic and kinetic principles that govern their therapeutic utility.
Topics: Adipocytes; Adipose Tissue; Animals; Energy Metabolism; Humans; Mice; Mitochondria; Oxidation-Reduction; Rats; Thermogenesis; Uncoupling Protein 1
PubMed: 30503034
DOI: 10.1016/j.cmet.2018.11.002 -
Nature Reviews. Molecular Cell Biology Jun 2021Brown and beige adipocytes are mitochondria-enriched cells capable of dissipating energy in the form of heat. These thermogenic fat cells were originally considered to... (Review)
Review
Brown and beige adipocytes are mitochondria-enriched cells capable of dissipating energy in the form of heat. These thermogenic fat cells were originally considered to function solely in heat generation through the action of the mitochondrial protein uncoupling protein 1 (UCP1). In recent years, significant advances have been made in our understanding of the ontogeny, bioenergetics and physiological functions of thermogenic fat. Distinct subtypes of thermogenic adipocytes have been identified with unique developmental origins, which have been increasingly dissected in cellular and molecular detail. Moreover, several UCP1-independent thermogenic mechanisms have been described, expanding the role of these cells in energy homeostasis. Recent studies have also delineated roles for these cells beyond the regulation of thermogenesis, including as dynamic secretory cells and as a metabolic sink. This Review presents our current understanding of thermogenic adipocytes with an emphasis on their development, biological functions and roles in systemic physiology.
Topics: Adipocytes, Beige; Adipocytes, Brown; Animals; Energy Metabolism; Humans; Lipid Metabolism; Thermogenesis; Uncoupling Protein 1
PubMed: 33758402
DOI: 10.1038/s41580-021-00350-0 -
Cell Metabolism Apr 2022Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes...
Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program. When re-uptaken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-γ signaling and the levels of mitochondrial proteins, including UCP1. Their removal via the phagocytic activity of BAT-resident macrophages is instrumental in preserving BAT physiology. Depletion of macrophages in vivo causes the abnormal accumulation of extracellular mitochondrial vesicles in BAT, impairing the thermogenic response to cold exposure. These findings reveal a homeostatic role of tissue-resident macrophages in the mitochondrial quality control of BAT.
Topics: Adipocytes, Brown; Adipose Tissue, Brown; Macrophages; Mitochondria; Thermogenesis; Uncoupling Protein 1
PubMed: 35305295
DOI: 10.1016/j.cmet.2022.02.016 -
Neuroscience Letters Mar 2019Maintenance of mammalian core body temperature within a narrow range is a fundamental homeostatic process to optimize cellular and tissue function, and to improve... (Review)
Review
Maintenance of mammalian core body temperature within a narrow range is a fundamental homeostatic process to optimize cellular and tissue function, and to improve survival in adverse thermal environments. Body temperature is maintained during a broad range of environmental and physiological challenges by central nervous system circuits that process thermal afferent inputs from the skin and the body core to control the activity of thermoeffectors. These include thermoregulatory behaviors, cutaneous vasomotion (vasoconstriction and, in humans, active vasodilation), thermogenesis (shivering and brown adipose tissue), evaporative heat loss (salivary spreading in rodents, and human sweating). This review provides an overview of the central nervous system circuits for thermoregulatory reflex regulation of thermoeffectors.
Topics: Animals; Body Temperature; Body Temperature Regulation; Humans; Neural Pathways; Shivering; Skin Temperature; Thermogenesis
PubMed: 30586638
DOI: 10.1016/j.neulet.2018.11.027 -
Handbook of Experimental Pharmacology 2019Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence... (Review)
Review
Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence and significance to metabolic fitness in adult humans have been widely realized. The ability of active brown fat to expend high amounts of energy has raised interest in stimulating thermogenesis therapeutically to treat metabolic diseases related to obesity and type 2 diabetes. In parallel, there has been a surge of research aimed at understanding the biology of rodent and human brown fat development, its remarkable metabolic properties, and the phenomenon of white fat browning, in which white adipocytes can be converted into brown like adipocytes with similar thermogenic properties. Here, we review the current understanding of the developmental and metabolic pathways involved in forming thermogenic adipocytes, and highlight some of the many unknown functions of brown fat that make its study a rich and exciting area for future research.
Topics: Adipogenesis; Adipose Tissue, Brown; Adipose Tissue, White; Adult; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Thermogenesis
PubMed: 30203328
DOI: 10.1007/164_2018_168 -
ELife Jan 2022Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves...
Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas1 receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. knockout mice () and knockout mice () displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from display metabolic abnormalities consistent with those seen in the and knockout mice. In contrast, impaired thermogenesis of obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids, and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel potential therapeutic targets for the treatment of metabolic disorders.
Topics: Angiotensin-Converting Enzyme 2; Animals; Energy Metabolism; Male; Mice; Mice, Inbred C57BL; Signal Transduction; Thermogenesis
PubMed: 35014608
DOI: 10.7554/eLife.72266 -
Endocrine Reviews Mar 2023Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target... (Review)
Review
Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance, and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated from BAT thermogenic activity, as for example in insulin-resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride lipolysis. This lipolytic BAT response is intertwined with that of white adipose (WAT) and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body's thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically, and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in WAT and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.
Topics: Humans; Adipose Tissue, Brown; Obesity; Thermogenesis; Energy Metabolism; Cardiovascular Diseases
PubMed: 35640259
DOI: 10.1210/endrev/bnac015 -
American Journal of Physiology.... Mar 2021Brown adipose tissue (BAT) has been encouraged as a potential treatment for obesity and comorbidities due to its thermogenic activity capacity and contribution to energy... (Review)
Review
Brown adipose tissue (BAT) has been encouraged as a potential treatment for obesity and comorbidities due to its thermogenic activity capacity and contribution to energy expenditure. Some interventions such as cold and β-adrenergic drugs are able to activate BAT thermogenesis as well as promote differentiation of white adipocytes into brown-like cells (browning), enhancing the thermogenic activity of these cells. In this mini-review, we discuss new mechanisms related to BAT and energy expenditure. In this regard, we will also discuss recent studies that have revealed the existence of important secretory molecules from BAT "batokines" that act in autocrine, paracrine, and endocrine mechanisms, which in turn may explain some of the beneficial roles of BAT on whole body glucose and fat metabolism. Finally, we will discuss new insights related to BAT thermogenesis with an additional focus on the distinct features of BAT metabolism between rodents and humans.
Topics: Adipocytes, White; Adipose Tissue, Brown; Animals; Energy Metabolism; Glucose; Humans; Thermogenesis
PubMed: 33459179
DOI: 10.1152/ajpendo.00310.2020 -
Cell Jan 2023Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by...
Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.
Topics: Mice; Animals; Humans; Adipose Tissue, Brown; Hypothalamus; Thermogenesis; Retina; Retinal Ganglion Cells; Glucose
PubMed: 36669474
DOI: 10.1016/j.cell.2022.12.024