Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue (original) (raw)
Related papers
Functional differentiation of white and brown adipocytes
BioEssays, 1997
Adipose tissue plays an important role in mammalian energy equilibrium not only as a lipid-dissipating, i.e. energy-storing, tissue (white adipose tissue), but also as an energy-dissipating one (brown adipose tissue). Brown adipocytes have the ability of facultative heat production due to a unique mitochondria1 protein, the uncoupling protein (UCP). Differentiation of white and (to a lesser extent) brown adipocytes has been studied in different cell culture systems, which has led to the identification of external inducers, second messenger pathways and transcription factors involved in adipocyte differentiation. Functional differentiation of white adipocytes implies adipose conversion, whereas in brown adipocytes it insinuates additionally the development of a thermogenic function. This review discusses recent advances in the elucidation of the pathways responsible for, and the molecular bases of, adipose conversion on the one hand and development of the Accepted thermogenic properties of brown adipocytes on the other. December 23 1996 10% FCS, 4 nM insulin 7-10% FCS, 17 nM insulin, 1 nM T3 171 nM insulin, 1 nM T3, transferrin, 500 nM insulin, 0 2 nM T3, transferrin 10% FCS, 50 nM insulin, 50 nM T3, 100 nM dexamethasone (glucocorticoid)
European Journal of Endocrinology, 2014
In mammals, adipocytes are lipid-laden cells making up the parenchyma of the multi-depot adipose 3 organ. White adipocytes store lipids for release as free fatty acids during fasting periods; brown 4 adipocytes burn glucose and lipids to maintain thermal homeostasis. A third type of adipocyte, the 5 pink adipocyte, has recently been characterised in mouse subcutaneous fat depots during pregnancy 6 and lactation. Pink adipocytes are mammary gland alveolar epithelial cells whose role is to produce 7 and secrete milk. Emerging evidence suggests that they derive from the transdifferentiation of 8 subcutaneous white adipocytes. The functional response of the adipose organ to a range of 9 metabolic and environmental challenges highlights its extraordinary plasticity. Cold exposure 10 induces an increase in the "brown" component of the organ, to meet the increased thermal demand; 11 in states of positive energy balance the "white" component expands to store excess nutrients; 12 finally, the "pink" component develops in subcutaneous depots during pregnancy to ensure litter 13 feeding. At the cell level plasticity is provided not only by stem cell proliferation and differentiation 14 but also, distinctively, by direct transdifferentiation of fully-differentiated adipocytes by stimuli that 15 induce genetic expression reprogramming and through it a change in phenotype and, consequently, 16 function. A greater understanding of adipocyte transdifferentiation mechanisms would have the 17 potential to shed light on their biology as well as inspire novel therapeutic strategies against 18 metabolic syndrome ("browning") and breast cancer ("pinking"). 19 20 21 22
Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis
The Journal of clinical investigation, 2015
Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance. Two types of thermogenic adipocytes with distinct developmental and anatomical features exist in rodents and humans: classical brown adipocytes and beige (also referred to as brite) adipocytes. While classical brown adipocytes are located mainly in dedicated BAT depots of rodents and infants, beige adipocytes sporadically reside with white adipocytes and emerge in response to certain environmental cues, such as chronic cold exposure, a process often referred to as "browning" of white adipose tissue. Recent studies indicate the existence of beige adipocytes in adult humans, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, including type 2 diabetes. This Review aims to cover recent progress in our understanding of the anatomical, developmental, and functional characteristics of brown...
F1000 - Post-publication peer review of the biomedical literature, 2012
Brown fat defends against hypothermia and obesity through thermogenesis mediated by mitochondrial UCP1. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here we report the cloning of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we show that deposits of brown fat previously observed in adult humans are composed of beige adipose cells. These data illustrate a new cell type with therapeutic potential in mouse and human.
Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
Cell, 2012
Brown fat defends against hypothermia and obesity through thermogenesis mediated by mitochondrial UCP1. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here we report the cloning of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we show that deposits of brown fat previously observed in adult humans are composed of beige adipose cells. These data illustrate a new cell type with therapeutic potential in mouse and human.
AJP: Cell Physiology, 2014
OBESITY IS A METABOLIC DISEASE that is assuming epidemic proportions. Obesity is caused by an imbalance between energy intake and energy expenditure, resulting in an excess of body fat. Obesity-associated diseases include diabetes, insulin resistance, dyslipidemia, liver steatosis, hypertension, heart diseases, and increased incidence of certain cancers. Few pharmacological approaches are available for the treatment of obesity, apart from dieting and changes in lifestyle, and new drugs and strategies are required.
EMBO reports, 2014
Thermogenesis in brown adipocytes, conferred by mitochondrial uncoupling protein 1 (UCP1), is receiving great attention because metabolically active brown adipose tissue may protect humans from metabolic diseases. In particular, the thermogenic function of brown-like adipocytes in white adipose tissue, known as brite (or beige) adipocytes, is currently of prime interest. A valid procedure to quantify the specific contribution of UCP1 to thermogenesis is thus of vital importance. Adrenergic stimulation of lipolysis is a common way to activate UCP1. We here report, however, that in this frequently applied setup, taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured brown and brite adipocytes. By the application of these findings, we demonstrate that UCP1 is functionally thermogenic in intact brite adipocytes and adrenergic UCP1 activation is largely dependent on adipose triglyceride lipase (ATGL) rather than hormone sensi...
Identification and characterization of distinct murine brown adipocyte lineages
2020
Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. While increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Using single cell RNA sequencing of the stromal vascular fraction of murine BAT and analysis of 67 brown preadipocyte and adipocyte clones we unravel heterogeneity within brown preadipocytes. Statistical analysis of gene expression profiles from these clones identifies markers distinguishing brown adipocyte lineages. We confirm the presence of distinct brown adipocyte populations in vivo using three identified markers; Eif5, Tcf25, and Bin1. Functionally, we demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that Bin1 marks a dormant brown adipocyte type. The existence of multiple brown adipocyte lineages suggests distinct functional properties of BAT depending on its cellular composition, with potentially ...