scholarly journals The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

2000 ◽  
Vol 345 (2) ◽  
pp. 161-179 ◽  
Author(s):  
Daniel RICQUIER ◽  
Frédéric BOUILLAUD
Keyword(s):  
Metabolic Pathways ◽  
Uncoupling Protein ◽  
The Body ◽  
Genetic Studies ◽  
Anion Transporter ◽  
Ucp3 Gene ◽  
Brown Adipose ◽  
Nadh Ratio ◽  
Plant Uncoupling Protein ◽  
Inflammatory Processes

Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton/anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest that UCP2 and UCP3 play a part in energy expenditure in humans. The UCPs may also be involved in adaptation of cellular metabolism to an excessive supply of substrates in order to regulate the ATP level, the NAD+/NADH ratio and various metabolic pathways, and to contain superoxide production. A major goal will be the analysis of mice that either lack the UCP2 or UCP3 gene or overexpress these genes. Other aims will be to investigate the possible roles of UCP2 and UCP3 in response to oxidative stress, lipid peroxidation, inflammatory processes, fever and regulation of temperature in certain specific parts of the body.

Glucocorticoids and regulation of brown adipose tissue in humans – physiological and pathophysiological considerations

2017 ◽  
Vol 86 (3) ◽  
pp. 227
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Adrenergic Stimulation ◽  
Therapeutic Goals ◽  
Bat Activity ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Differentiation And Proliferation

This review discusses the effects of glucocorticoids (GCs) on brown adipose tissue (BAT) in the context of obesity prevention and therapy. Due to the unique expression of the uncoupling protein 1 (UCP1), BAT is capable of non‑shivering thermogenesis, also defined as a metabolic heat production, related to increased metabolic rate. All processes that contribute to an increase in activity and/or quantity of BAT are able to upturn metabolism, and thus enable the above therapeutic goals to be achieved. GCs may stimulate BAT differentiation and proliferation. In the case of differentiation, the opposite effect of GCs has been also described. Within white adipose tissue (WAT) GCs inhibit the formation of so called beige adipocytes that are functionally and morphologically similar to the adipocytes from BAT. The activity of GCs with concomitant inhibition of WAT browning is mediated by the induction of microRNA-27b (MIR27B) expression. GCs are responsible for the decline in BAT activity as the body ages. Depriving the body of an enzyme responsible for local reduction of cortisone into an active GC‑cortisol in BAT (11β‑hydroxysteroid dehydrogenase type 1; 11β‑HSD1) prevents the reduction of BAT activity. The effects of high doses of GCs on BAT generally depend on the exposure time. Prolonged elevation in GCs level decreases BAT activity. During adrenergic stimulation the effect of GCs on BAT is ambiguous, because both decrease and increase in activity has been described. A full understanding of the GCs impact on brown remodeling in WAT may reveal a discovery of a novel preventive and therapeutic strategies for obesity and possibly other metabolic disorders.

Enlargement of Interscapular Brown Adipose Tissue in Growth Hormone Antagonist Transgenic and in Growth Hormone Receptor Gene-Disrupted Dwarf Mice

2003 ◽  
Vol 228 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Yuesheng Li ◽  
Joanne R. Knapp ◽  
John J. Kopchick
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Northern Analysis ◽  
Interscapular Brown Adipose Tissue ◽  
Triglyceride Accumulation ◽  
Brown Adipose ◽  
Dwarf Mice

Growth hormone (GH) acts on adipose tissue by accelerating fat expenditure, preventing triglyceride accumulation, and facilitating lipid mobilization. To investigate whether GH is involved in the development and metabolism of interscapular brown adipose tissue (BAT), a site of nonshivering thermogenesis, we employed three lines of transgenic mice. Two of the lines are dwarf due to expression of a GH antagonist (GHA) or disruption of the GH receptor/binding-protein gene. A third mouse line is giant due to overexpression of a bovine GH (bGH) transgene. We have found that the body weights of those animals are proportional to their body lengths at 10 weeks of age. However, GHA dwarf mice tend to catch up with the nontransgenic (NT) littermates in body weight but not in body length at 52 weeks of age. The increase of body mass index (BMI) for GHA mice accelerates rapidly relative to controls as a function of age. We have also observed that BAT in both dwarf mouse lines but not in giant mice is enlarged in contrast to nontransgenic littermates. This enlargement occurs as a function of age. Northern analysis suggests that BAT can be a GH-responsive tissue because GHR/BP mRNAs were found there. Finally, the level of uncoupling protein-1 (UCP1) RNA was found to be higher in dwarf mice and lower in giant animals relative to controls, suggesting that GH-mediated signaling may negatively regulate UCP1 gene expression in BAT.

scholarly journals Potential Crosstalk between Fructose and Melatonin: A New Role of Melatonin—Inhibiting the Metabolic Effects of Fructose

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Francisco J. Valenzuela-Melgarejo ◽  
Claudia Caro-Díaz ◽  
Gerardo Cabello-Guzmán
Keyword(s):  
Body Weight ◽  
Metabolic Pathways ◽  
Uncoupling Protein ◽  
Weight Ratio ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Metabolic Effects ◽  
Beta Oxidation ◽  
Clock Gene Expression ◽  
Harmful Effects

Increased consumption of energy-dense foods such as fructose-rich syrups represents one of the significant, growing concerns related to the alarming trend of overweight, obesity, and metabolic disorders worldwide. Metabolic pathways affected by fructose involve genes related to lipogenesis/lipolysis, beta-oxidation, mitochondrial biogenesis, gluconeogenesis, oxidative phosphorylation pathways, or altering of circadian production of insulin and leptin. Moreover, fructose can be a risk factor during pregnancy elevating the risk of preterm delivery, hypertension, and metabolic impairment of the mother and fetus. Melatonin is a chronobiotic and homeostatic hormone that can modulate the harmful effects of fructose via clock gene expression and metabolic pathways, modulating the expression of PPARγ, SREBF-1 (SREBP-1), hormone-sensitive lipase, C/EBP-α genes, NRF-1, PGC1α, and uncoupling protein-1. Moreover, this hormone has the capacity in the rat of reverting the harmful effects of fructose, increasing the body weight and weight ratio of the liver, and increasing the body weight and restoring the glycemia from mothers exposed to fructose. The aim of this review is to show the potential crosstalk between fructose and melatonin and their potential role during pregnancy.

scholarly journals Brown adipose tissue development and function and its impact on reproduction

2018 ◽  
Vol 238 (1) ◽  
pp. R53-R62 ◽  
Author(s):  
Michael E Symonds ◽  
Peter Aldiss ◽  
Neele Dellschaft ◽  
James Law ◽  
Hernan P Fainberg ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Maternal Obesity ◽  
Thermal Environment ◽  
Uncoupling Protein ◽  
The Body ◽  
Substantial Impact ◽  
Brown Adipose ◽  
Fat Depot

Although brown adipose tissue (BAT) is one of the smallest organs in the body, it has the potential to have a substantial impact on both heat production as well as fat and carbohydrate metabolism. This is most apparent at birth, which is characterised with the rapid appearance and activation of the BAT specific mitochondrial uncoupling protein (UCP)1 in many large mammals. The amount of brown fat then gradually declines with age, an adaptation that can be modulated by the thermal environment. Given the increased incidence of maternal obesity and its potential transmission to the mother’s offspring, increasing BAT activity in the mother could be one mechanism to prevent this cycle. To date, however, all rodent studies investigating maternal obesity have been conducted at standard laboratory temperature (21°C), which represents an appreciable cold challenge. This could also explain why offspring weight is rarely increased, suggesting that future studies would benefit from being conducted at thermoneutrality (~28°C). It is also becoming apparent that each fat depot has a unique transcriptome and show different developmental pattern, which is not readily apparent macroscopically. These differences could contribute to the retention of UCP1 within the supraclavicular fat depot, the most active depot in adult humans, increasing heat production following a meal. Despite the rapid increase in publications on BAT over the past decade, the extent to which modifications in diet and/or environment can be utilised to promote its activity in the mother and/or her offspring remains to be established.

scholarly journals Role of Metabolism in Bone Development and Homeostasis

2020 ◽  
Vol 21 (23) ◽  
pp. 8992
Author(s):  
Akiko Suzuki ◽  
Mina Minamide ◽  
Chihiro Iwaya ◽  
Kenichi Ogata ◽  
Junichi Iwata
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Bone Cells ◽  
Bone Development ◽  
Bone Matrix ◽  
The Body ◽  
Cellular Functions ◽  
Genetic Studies ◽  
Cellular Dysfunction

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.

Adrenergically stimulated blood flow in brown adipose tissue is not dependent on thermogenesis

2015 ◽  
Vol 308 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Gustavo Abreu-Vieira ◽  
Carolina E. Hagberg ◽  
Kirsty L. Spalding ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Temperature Acclimation ◽  
The Body ◽  
Doppler Imaging ◽  
Dependent Manner ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis relies on blood flow to be supplied with nutrients and oxygen and for the distribution of the generated heat to the rest of the body. Therefore, it is fundamental to understand the mechanisms by which blood flow is regulated and its relation to thermogenesis. Here, we present high-resolution laser-Doppler imaging (HR-LDR) as a novel method for noninvasive in vivo measurement of BAT blood flow in mice. Using HR-LDR, we found that norepinephrine stimulation increases BAT blood flow in a dose-dependent manner and that this response is profoundly modulated by environmental temperature acclimation. Surprisingly, we found that mice lacking uncoupling protein 1 (UCP1) have fully preserved BAT blood flow response to norepinephrine despite failing to perform thermogenesis. BAT blood flow was not directly correlated to systemic glycemia, but glucose injections could transiently increase tissue perfusion. Inguinal white adipose tissue, also known as a brite/beige adipose tissue, was also sensitive to cold acclimation and similarly increased blood flow in response to norepinephrine. In conclusion, using a novel noninvasive method to detect BAT perfusion, we demonstrate that adrenergically stimulated BAT blood flow is qualitatively and quantitatively fully independent of thermogenesis, and therefore, it is not a reliable parameter for the estimation of BAT activation and heat generation.

scholarly journals Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet–Fed Mice through Increased Thermogenesis

2020 ◽  
Vol 150 (8) ◽  
pp. 2131-2138 ◽  
Author(s):  
Fang Zhou ◽  
Jielong Guo ◽  
Xue Han ◽  
Yunxiao Gao ◽  
Qimin Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
The Body ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Polyphenolic Extract ◽  
Brown Adipose

ABSTRACT Background Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. Objectives In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)–fed obese mice. Methods The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. Results After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. Conclusions Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

scholarly journals Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

2015 ◽  
Vol 112 (5) ◽  
pp. 1607-1612 ◽  
Author(s):  
Willem J. Laursen ◽  
Marco Mastrotto ◽  
Dominik Pesta ◽  
Owen H. Funk ◽  
Jena B. Goodman ◽  
...  
Keyword(s):  
Body Temperature ◽  
Molecular Mechanisms ◽  
Brain Temperature ◽  
Uncoupling Protein ◽  
Ground Squirrels ◽  
The Body ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as −2.9 °C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. We report, using differential transcriptomics alongside immunohistologic and biochemical analyses, that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) express mitochondrial uncoupling protein 1 (UCP1). The expression changes seasonally, with higher expression during hibernation compared with the summer active state. Functional and pharmacologic analyses show that squirrel UCP1 acts as the typical thermogenic protein in vitro. Accordingly, we found that mitochondria isolated from torpid squirrel brain show a high level of palmitate-induced uncoupling. Furthermore, torpid squirrels during the hibernation season keep their brain temperature significantly elevated above ambient temperature and that of the rest of the body, including brown adipose tissue. Together, our findings suggest that UCP1 contributes to local thermogenesis in the squirrel brain, and thus supports nervous tissue function at low body temperature during hibernation.

scholarly journals Seasonal changes in brown adipose tissue mitochondria in a mammalian hibernator: from gene expression to function

2016 ◽  
Vol 311 (2) ◽  
pp. R325-R336 ◽  
Author(s):  
Mallory A. Ballinger ◽  
Clair Hess ◽  
Max W. Napolitano ◽  
James A. Bjork ◽  
Matthew T. Andrews
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Mtdna Copy Number ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Content ◽  
Mitochondrial Proteome ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Brown adipose tissue (BAT) is a thermogenic organ that is vital for hibernation in mammals. Throughout the hibernation season, BAT mitochondrial uncoupling protein 1 (UCP1) enables rapid rewarming from hypothermic torpor to periodic interbout arousals (IBAs), as energy is dissipated as heat. However, BAT's unique ability to rewarm the body via nonshivering thermogenesis is not necessary outside the hibernation season, suggesting a potential seasonal change in the regulation of BAT function. Here, we examined the BAT mitochondrial proteome and mitochondrial bioenergetics in the thirteen-lined ground squirrel ( Ictidomys tridecemlineatus) across four time points: spring, fall, torpor, and IBA. Relative mitochondrial content of BAT was estimated by measuring BAT pad mass, UCP1 protein content, and mitochondrial DNA (mtDNA) copy number. BAT mtDNA content was significantly lower in spring compared with torpor and IBA ( P < 0.05). UCP1 mRNA and protein levels were highest during torpor and IBA. Respiration rates of isolated BAT mitochondria were interrogated at each complex of the electron transport chain. Respiration at complex II was significantly higher in torpor and IBA compared with spring ( P < 0.05), suggesting an enhancement in mitochondrial respiratory capacity during hibernation. Additionally, proteomic iTRAQ labeling identified 778 BAT mitochondrial proteins. Proteins required for mitochondrial lipid translocation and β-oxidation were upregulated during torpor and IBA and downregulated in spring. These data imply that BAT bioenergetics and mitochondrial content are not static across the year, despite the year-round presence of UCP1.

UCP1-independent thermogenesis

2020 ◽  
Vol 477 (3) ◽  
pp. 709-725 ◽  
Author(s):  
Anna Roesler ◽  
Lawrence Kazak
Keyword(s):  
Energy Expenditure ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Cell Types ◽  
Energy Balance Equation ◽  
The Body ◽  
Protonmotive Force ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

Obesity results from energy imbalance, when energy intake exceeds energy expenditure. Brown adipose tissue (BAT) drives non-shivering thermogenesis which represents a powerful mechanism of enhancing the energy expenditure side of the energy balance equation. The best understood thermogenic system in BAT that evolved to protect the body from hypothermia is based on the uncoupling of protonmotive force from oxidative phosphorylation through the actions of uncoupling protein 1 (UCP1), a key regulator of cold-mediated thermogenesis. Similarly, energy expenditure is triggered in response to caloric excess, and animals with reduced thermogenic fat function can succumb to diet-induced obesity. Thus, it was surprising when inactivation of Ucp1 did not potentiate diet-induced obesity. In recent years, it has become clear that multiple thermogenic mechanisms exist, based on ATP sinks centered on creatine, lipid, or calcium cycling, along with Fatty acid-mediated UCP1-independent leak pathways driven by the ADP/ATP carrier (AAC). With a key difference between cold- and diet-induced thermogenesis being the dynamic changes in purine nucleotide (primarily ATP) levels, ATP-dependent thermogenic pathways may play a key role in diet-induced thermogenesis. Additionally, the ubiquitous expression of AAC may facilitate increased energy expenditure in many cell types, in the face of over feeding. Interest in UCP1-independent energy expenditure has begun to showcase the therapeutic potential that lies in refining our understanding of the diversity of biochemical pathways controlling thermogenic respiration.

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