scholarly journals Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 319
Author(s):  
Christel L. Roth ◽  
Filippo Molica ◽  
Brenda R. Kwak
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
High Density Lipoproteins ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes

Despite continuous medical advances, atherosclerosis remains the prime cause of mortality worldwide. Emerging findings on brown and beige adipocytes highlighted that these fat cells share the specific ability of non-shivering thermogenesis due to the expression of uncoupling protein 1. Brown fat is established during embryogenesis, and beige cells emerge from white adipose tissue exposed to specific stimuli like cold exposure into a process called browning. The consecutive energy expenditure of both thermogenic adipose tissues has shown therapeutic potential in metabolic disorders like obesity and diabetes. The latest data suggest promising effects on atherosclerosis development as well. Upon cold exposure, mice and humans have a physiological increase in brown adipose tissue activation and browning of white adipocytes is promoted. The use of drugs like β3-adrenergic agonists in murine models induces similar effects. With respect to atheroprotection, thermogenic adipose tissue activation has beneficial outcomes in mice by decreasing plasma triglycerides, total cholesterol and low-density lipoproteins, by increasing high-density lipoproteins, and by inducing secretion of atheroprotective adipokines. Atheroprotective effects involve an unaffected hepatic clearance. Latest clinical data tend to find thinner atherosclerotic lesions in patients with higher brown adipose tissue activity. Strategies for preserving healthy arteries are a major concern for public health.

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 CD137 negatively affects “browning” of white adipose tissue during cold exposure

2020 ◽  
Vol 295 (7) ◽  
pp. 2034-2042 ◽  
Author(s):  
Raj Kamal Srivastava ◽  
Annalena Moliner ◽  
Ee-Soo Lee ◽  
Emily Nickles ◽  
Eunice Sim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Surface Protein ◽  
Negative Regulator ◽  
Subcutaneous White Adipose Tissue ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
A Cell

Prolonged cold exposure stimulates the formation of brownlike adipocytes expressing UCP1 (uncoupling-protein-1) in subcutaneous white adipose tissue which, together with classical brown adipose tissue, contributes to maintaining body temperature in mammals through nonshivering thermogenesis. The mechanisms that regulate the formation of these cells, alternatively called beige or brite adipocytes, are incompletely understood. Here we report that mice lacking CD137, a cell surface protein used in several studies as a marker for beige adipocytes, showed elevated levels of thermogenic markers, including UCP1, increased numbers of beige adipocyte precursors, and expanded UCP1-expressing cell clusters in inguinal white adipose tissue after chronic cold exposure. CD137 knockout mice also showed enhanced cold resistance. These results indicate that CD137 functions as a negative regulator of “browning” in white adipose tissue and call into question the use of this protein as a functional marker for beige adipocytes.

scholarly journals The Effect of Hyperbaric Therapy on Brown Adipose Tissue in Rats

2021 ◽  
Vol 18 (17) ◽  
pp. 9165
Author(s):  
Chang-Hyung Lee ◽  
Young-A Choi ◽  
Sung-Jin Heo ◽  
Parkyong Song
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Brown Adipose ◽  
Ucp1 Expression

Brown adipose tissue (BAT) plays an important role in thermogenic regulation, which contributes to alleviating diet-induced obesity through uncoupling protein 1 (UCP1) expression. While cold exposure and physical exercise are known to increase BAT development and UCP1 expression, the contribution of hyperbaric oxygen (HBO) therapy to BAT maturation remains largely unknown. Here, we show that HBO treatment sufficiently increases BAT volumes and thermogenic protein levels in Sprague-Dawley rats. Through 18F-FDG PET/CT analysis, we found that exposure to high-pressure oxygen (1.5–2.5 ATA) for 7 consecutive days increased radiolabeled glucose uptake and BAT development to an extent comparable to cold exposure. Consistent with BAT maturation, thermogenic protein levels, such as those of UCP1 and peroxisome proliferator-activated receptor γ coactivator 1α (PGC−1α), were largely increased by HBO treatment. Taken together, we suggest HBO therapy as a novel method of inducing BAT development, considering its therapeutic potential for the treatment of metabolic disorders.

scholarly journals Brown Adipose Tissue Growth and Development

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Michael E. Symonds
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Tissue Growth ◽  
Brown Fat ◽  
Prevention Strategies ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Substantial Rise

Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue

1995 ◽  
Vol 269 (1) ◽  
pp. R38-R47 ◽  
Author(s):  
J. M. Matz ◽  
M. J. Blake ◽  
H. M. Tatelman ◽  
K. P. Lavoi ◽  
N. J. Holbrook
Keyword(s):  
Adipose Tissue ◽  
Heat Shock ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Elevated Temperatures ◽  
Uncoupling Protein ◽  
Hsp70 Expression ◽  
Mitochondrial Uncoupling ◽  
Ambient Temperatures ◽  
Brown Adipose

The accumulation of heat shock proteins (HSPs) after the exposure of cells or organisms to elevated temperatures is well established. It is also known that a variety of other environmental and cellular metabolic stressors can induce HSP synthesis. However, few studies have investigated the effect of cold temperature on HSP expression. Here we report that exposure of Institute of Cancer Research (ICR) mice to cold ambient temperatures results in a tissue-selective induction of HSPs in brown adipose tissue (BAT) coincident with the induction of mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is associated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to heat and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to cold exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic receptors through, as yet, undetermined signal transduction pathways. Thermogenesis results from an increase in activity and synthesis of several metabolic enzymes in BAT of animals exposed to cold challenge. The concomitant increase in HSPs may function to facilitate the translocation and activity of the enzymes involved in this process.

scholarly journals PACAP is essential for the adaptive thermogenic response of brown adipose tissue to cold exposure

2014 ◽  
Vol 222 (3) ◽  
pp. 327-339 ◽  
Author(s):  
Abdoulaye Diané ◽  
Nikolina Nikolic ◽  
Alexander P Rudecki ◽  
Shannon M King ◽  
Drew J Bowie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Morphological Properties ◽  
Brown Adipose ◽  
Thermogenic Response

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed neuropeptide that acts as a neurotransmitter, neuromodulator, neurotropic factor, neuroprotectant, secretagogue,and neurohormone. Owing to its pleiotropic biological actions, knockout ofPacap(Adcyap1) has been shown to induce several abnormalities in mice such as impaired thermoregulation. However, the underlying physiological and molecular mechanisms remain unclear. A previous report has shown that cold-exposedPacapnull mice cannot supply appropriate levels of norepinephrine (NE) to brown adipocytes. Therefore, we hypothesized that exogenous NE would rescue the impaired thermogenic response ofPacapnull mice during cold exposure. We compared the adaptive thermogenic capacity ofPacap−/−toPacap+/+mice in response to NE when housed at room temperature (24 °C) and after a 3.5-week cold exposure (4 °C). Biochemical parameters, expression of thermogenic genes, and morphological properties of brown adipose tissue (BAT) and white adipose tissue (WAT) were also characterized. Results showed that there was a significant effect of temperature, but no effect of genotype, on the resting metabolic rate in conscious, unrestrained mice. However, the normal cold-induced increase in the basal metabolic rate and NE-induced increase in thermogenesis were severely blunted in cold-exposedPacap−/−mice. These changes were associated with altered substrate utilization, reduced β3-adrenergic receptor (β3-Ar(Adrb3)) and hormone-sensitive lipase (Hsl(Lipe)) gene expression, and increased fibroblast growth factor 2 (Fgf2) gene expression in BAT. Interestingly,Pacap−/−mice had depleted WAT depots, associated with upregulated uncoupling protein 1 expression in inguinal WATs. These results suggest that the impairment of adaptive thermogenesis inPacapnull mice cannot be rescued by exogenous NE perhaps in part due to decreased β3-Ar-mediated BAT activation.

Cold exposure potentiates the effect of insulin on in vivo glucose uptake

1987 ◽  
Vol 253 (2) ◽  
pp. E179-E186 ◽  
Author(s):  
A. L. Vallerand ◽  
F. Perusse ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Skeletal Muscles ◽  
Insulin Injection ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
Insulin Responses

The effects of cold exposure (48 h at 4 degrees C) and insulin injection (0.5 U/kg iv) on the rates of net 2-[3H]deoxyglucose uptake (Ki) in peripheral tissues were investigated in warm-acclimated rats (25 degrees C). Cold exposure and insulin treatment independently increased Ki values in skeletal muscles (soleus, extensor digitorum longus, and vastus lateralis), heart, white adipose tissue (subcutaneous, gonadal, and retroperitoneal), and brown adipose tissue (P less than 0.01). The effects of cold exposure were particularly evident in brown adipose tissue where the Ki increased greater than 100 times. When the two treatments were combined (insulin injection in cold-exposed rats), it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an "insulin-like" effect on Ki that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake.

scholarly journals ChREBP-β regulates thermogenesis in brown adipose tissue

2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Active Form ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Metabolic Remodeling

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.

scholarly journals Genome-Wide Identification and Characterization of Long Noncoding RNAs of Brown to White Adipose Tissue Transformation in Goats

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 904 ◽  
Author(s):  
Linjie Wang ◽  
Xin Yang ◽  
Yuehua Zhu ◽  
Siyuan Zhan ◽  
Zhe Chao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Unsaturated Fatty Acids ◽  
Uncoupling Protein ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Brown Adipose ◽  
Perirenal Fat

Long noncoding RNAs (lncRNAs) play an important role in the thermogenesis and energy storage of brown adipose tissue (BAT). However, knowledge of the cellular transition from BAT to white adipose tissue (WAT) and the potential role of lncRNAs in goat adipose tissue remains largely unknown. In this study, we analyzed the transformation from BAT to WAT using histological and uncoupling protein 1 (UCP1) gene analyses. Brown adipose tissue mainly existed within the goat perirenal fat at 1 day and there was obviously a transition from BAT to WAT from 1 day to 1 year. The RNA libraries constructed from the perirenal adipose tissues of 1 day, 30 days, and 1 year goats were sequenced. A total number of 21,232 lncRNAs from perirenal fat were identified, including 5393 intronic-lncRNAs and 3546 antisense-lncRNAs. Furthermore, a total of 548 differentially expressed lncRNAs were detected across three stages (fold change ≥ 2.0, false discovery rate (FDR) < 0.05), and six lncRNAs were validated by qPCR. Furthermore, trans analysis found lncRNAs that were transcribed close to 890 protein-coding genes. Additionally, a coexpression network suggested that 4519 lncRNAs and 5212 mRNAs were potentially in trans-regulatory relationships (r > 0.95 or r < −0.95). In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the targeted genes were involved in the biosynthesis of unsaturated fatty acids, fatty acid elongation and metabolism, the citrate cycle, oxidative phosphorylation, the mitochondrial respiratory chain complex, and AMP-activated protein kinase (AMPK) signaling pathways. The present study provides a comprehensive catalog of lncRNAs involved in the transformation from BAT to WAT and provides insight into understanding the role of lncRNAs in goat brown adipogenesis.

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