scholarly journals Both liver-X receptor (LXR) isoforms control energy expenditure by regulating Brown Adipose Tissue activity

2010 ◽  
Vol 108 (1) ◽  
pp. 403-408 ◽  
Author(s):  
Marion Korach-André ◽  
Amena Archer ◽  
Rodrigo P. Barros ◽  
Paolo Parini ◽  
Jan-Åke Gustafsson
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Crucial Role ◽  
Energy Homeostasis ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Energy Regulation ◽  
Brown Adipose ◽  
Long Term Treatment

Brown adipocytes are multilocular lipid storage cells that play a crucial role in nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of brown fat cells that allows heat generation on sympathetic nervous system stimulation. As conventional transcriptional factors that are activated in various signaling pathways, liver-X receptors (LXRs) play important roles in many physiological processes. The role of LXRs in the regulation of energy homeostasis remains unclear, however. Female WT, LXRαβ−/−, LXRα−/−, and LXRβ−/− mice were fed with either a normal diet (ND) or a high-carbohydrate diet (HCD) supplemented with or without GW3965-LXR agonist. LXRαβ−/− mice exhibited higher energy expenditure (EE) as well as higher UCP1 expression in brown adipose tissue (BAT) compared with WT mice on the HCD. In addition, long-term treatment of WT mice with GW3965 showed lower EE at thermoneutrality (30 °C) and lower Ucp1 expression level in BAT. Furthermore, H&E staining of the BAT of LXRαβ−/− mice exhibited decreased lipid droplet size compared with WT mice on the HCD associated with a more intense UCP1-positive reaction. Quantification of triglyceride (TG) content in BAT showed lower TG accumulation in LXRβ−/− mice compared with WT mice. Surprisingly, GW3965 treatment increased TG content (twofold) in the BAT of WT and LXRα−/− mice but not in LXRβ−/− mice. Furthermore, glucose transporter (GLUT4) in the BAT of LXRα−/− and LXRβ−/− mice was sixfold and fourfold increased, respectively, compared with WT mice on the ND. These findings suggest that LXRα as well as LXRβ could play a crucial role in the regulation of energy homeostasis in female mice and may be a potential target for the treatment of obesity and energy regulation.

scholarly journals Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia

1993 ◽  
Vol 291 (1) ◽  
pp. 109-113 ◽  
Author(s):  
R Burcelin ◽  
J Kande ◽  
D Ricquier ◽  
J Girard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Time Course ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Diabetic Rats ◽  
Plasma Insulin Concentration ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.

scholarly journals ACE2 Pathway Regulates Thermogenesis and Energy Metabolism

2021 ◽  
Author(s):  
Xi Cao ◽  
Tingting Shi ◽  
Chuanhai Zhang ◽  
Wanzhu Jin ◽  
Lini Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Cold Stimulation ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Pka Pathway

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 Mas 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. ACE2 knockout mice (ACE2-/y), Mas knockout mice (Mas-/-), and the mice transplanted with brown adipose tissue from Mas-/- mice displayed impaired thermogenesis. In contrast, impaired thermogenesis of db/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of ACE2 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 therapeutic targets for the treatment of metabolic disorders.

Short-term resistance to diet-induced obesity in A/J mice is not associated with regulation of hypothalamic neuropeptides

2004 ◽  
Vol 287 (4) ◽  
pp. E662-E670 ◽  
Author(s):  
John W. Bullen ◽  
Mary Ziotopoulou ◽  
Linda Ungsunan ◽  
Jatin Misra ◽  
Ilias Alevizos ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Microarray Analysis ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Hypothalamic Neuropeptides ◽  
Fat Feeding

To investigate the mechanisms underlying long-term resistance of the A/J mouse strain to diet-induced obesity, we studied, over a period of 4 wk, the expression of uncoupling proteins in brown adipose tissue and the expression of hypothalamic neuropeptides known to regulate energy homeostasis and then used microarray analysis to identify other potentially important hypothalamic peptides. Despite increased caloric intake after 2 days of high-fat feeding, body weights of A/J mice remained stable. On and after 1 wk of high-fat feeding, A/J mice adjusted their food intake to consume the same amount of calories as mice fed a low-fat diet; thus their body weight and insulin, corticosterone, free fatty acid, and glucose levels remained unchanged for 4 wk. We found no changes in hypothalamic expression of several orexigenic and/or anorexigenic neuropeptides known to play an important role in energy homeostasis for the duration of the study. Uncoupling protein-2 mRNA expression in brown adipose tissue, however, was significantly upregulated after 2 days of high-fat feeding and tended to remain elevated for the duration of the 4-wk study. Gene array analysis revealed that several genes are up- or downregulated in response to 2 days and 1 wk of high-fat feeding. Real-time PCR analysis confirmed that expression of the hypothalamic IL-1 pathway (IL-1β, IL-1 type 1 and 2 receptors, and PPM1b/PP2C-β, a molecule that has been implicated in the inhibition of transforming growth factor-β-activated kinase-1-mediated IL-1 action) is altered after 2 days, but not 1 wk, of high-fat feeding. The role of additional molecules discovered by microarray analysis needs to be further explored in the future.

scholarly journals Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis

2021 ◽  
Vol 22 (4) ◽  
pp. 1530
Author(s):  
Katarzyna Maliszewska ◽  
Adam Kretowski
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Negative Energy ◽  
Metabolic Complications ◽  
Brown Adipose ◽  
Prevalence Of Obesity

The increased worldwide prevalence of obesity, insulin resistance, and their related metabolic complications have prompted the scientific world to search for new possibilities to combat obesity. Brown adipose tissue (BAT), due to its unique protein uncoupling protein 1 (UPC1) in the inner membrane of the mitochondria, has been acknowledged as a promising approach to increase energy expenditure. Activated brown adipocytes dissipate energy, resulting in heat production. In other words, BAT burns fat and increases the metabolic rate, promoting a negative energy balance. Moreover, BAT alleviates metabolic complications like dyslipidemia, impaired insulin secretion, and insulin resistance in type 2 diabetes. The aim of this review is to explore the role of BAT in total energy expenditure, as well as lipid and glucose homeostasis, and to discuss new possible activators of brown adipose tissue in humans to treat obesity and metabolic disorders.

scholarly journals Novel Browning Agents, Mechanisms, and Therapeutic Potentials of Brown Adipose Tissue

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Umesh D. Wankhade ◽  
Michael Shen ◽  
Hariom Yadav ◽  
Keshari M. Thakali
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Brown Adipocytes ◽  
Atp Production ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes

Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes. The recent appreciation that adult humans possess functional BAT strengthens this prospect. Furthermore, it has been identified that there are both classical brown adipocytes residing in dedicated BAT depots and “beige” adipocytes residing in white adipose tissue depots that can acquire BAT-like characteristics in response to environmental cues. This review aims to provide a brief overview of BAT research and summarize recent findings concerning the physiological, cellular, and developmental characteristics of brown adipocytes. In addition, some key genetic, molecular, and pharmacologic targets of BAT/Beige cells that have been reported to have therapeutic potential to combat obesity will be discussed.

scholarly journals ACE2 pathway regulates thermogenesis and energy metabolism

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Xi Cao ◽  
Tingting Shi ◽  
Chuanhai Zhang ◽  
Wanzhu Jin ◽  
Lini Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Cold Stimulation ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Pka Pathway

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. Ace2 knockout mice (Ace2-/y) and Mas1 knockout mice (Mas1-/-) displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from Mas1-/- display metabolic abnormalities consistent with those seen in the Ace2 and Mas1 knockout mice. In contrast, impaired thermogenesis of Leprdb/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of Ace2 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.

scholarly journals Role of the Central Melanocortin Circuitry in Adaptive Thermogenesis of Brown Adipose Tissue

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1550-1560 ◽  
Author(s):  
Adriana Voss-Andreae ◽  
Jonathan G. Murphy ◽  
Kate L. J. Ellacott ◽  
Ronald C. Stuart ◽  
Eduardo A. Nillni ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Pseudorabies Virus ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Uncoupling Protein 1 ◽  
Adaptive Thermogenesis ◽  
Melanocortin 4 Receptor ◽  
Brown Adipose

The central melanocortin 4 receptor (MC4R) plays a critical role in energy homeostasis, although little is known regarding its role in the regulation of adaptive thermogenesis of brown adipose tissue (BAT). Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we show that MC4R−/− and agouti-related peptide-treated mice are defective in HF diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R−/− mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R regulating sympathetically mediated IBAT thermogenesis and demonstrate that the MC4R is critically required for acute high-fat- and cold-induced IBAT thermogenesis.

scholarly journals Adipose tissue insulin resistance due to loss of PI3K p110α leads to decreased energy expenditure and obesity

2014 ◽  
Vol 306 (10) ◽  
pp. E1205-E1216 ◽  
Author(s):  
Victoria L. B. Nelson ◽  
Ya-Ping Jiang ◽  
Kathleen G. Dickman ◽  
Lisa M. Ballou ◽  
Richard Z. Lin
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Insulin Signaling ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Liver Steatosis ◽  
Cellular Respiration ◽  
Brown Adipose

Adipose tissue is a highly insulin-responsive organ that contributes to metabolic regulation. Insulin resistance in the adipose tissue affects systemic lipid and glucose homeostasis. Phosphoinositide 3-kinase (PI3K) mediates downstream insulin signaling in adipose tissue, but its physiological role in vivo remains unclear. Using Cre recombinase driven by the aP2 promoter, we created mice that lack the class 1A PI3K catalytic subunit p110α or p110β specifically in the white and brown adipose tissue. The loss of p110α, not p110β, resulted in increased adiposity, glucose intolerance and liver steatosis. Mice lacking p110α in adipose tissue exhibited a decrease in energy expenditure but no change in food intake or activity compared with control animals. This low energy expenditure is a consequence of low cellular respiration in the brown adipocytes caused by a decrease in expression of key mitochondrial genes including uncoupling protein-1. These results illustrate a critical role of p110α in the regulation of energy expenditure through modulation of cellular respiration in the brown adipose tissue and suggest that compromised insulin signaling in adipose tissue might be involved in the onset of obesity.

Leptin increases uncoupling protein expression and energy expenditure

1997 ◽  
Vol 273 (1) ◽  
pp. E226-E230 ◽  
Author(s):  
P. J. Scarpace ◽  
M. Matheny ◽  
B. H. Pollock ◽  
N. Tumer
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Food Consumption ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Sympathetic Outflow ◽  
Brown Adipose ◽  
Ad Libitum

In ob/ob mice, leptin increases energy expenditure and sympathetic outflow to brown adipose tissue (BAT). To test whether the mechanism of increased energy expenditure may involve increased thermogenesis in BAT, we acclimated normal rats to thermoneutrality for 2 wk followed by leptin administration for 1 wk. Some rats were food restricted for 1 wk to the level of food consumption in the leptin-treated ad libitum-fed rats, and the same rats were both food restricted and administered leptin for a second week. We examined oxygen consumption and uncoupling protein (UCP) expression in BAT. Leptin increased oxygen consumption after the 5th and 6th days in ad libitum-fed rats and after the 4th, 5th, and 6th days in food-restricted rats. Leptin increased BAT UCP mRNA levels greater than twofold in both ad libitum-fed and food-restricted rats. These data demonstrate a leptin-induced increase in energy expenditure in nonmutant rodents and suggest that one mechanism by which leptin increases energy expenditure is through increased thermogenesis in BAT, including increased expression of UCP.

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