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Nutrition, Brown and White Adipose Tissue

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 July 2018) | Viewed by 69201

Special Issue Editors

1. Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy, Lucio Lascaray Research Center, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain
2. CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
3. BIOARABA Institute of Health, Vitoria-Gasteiz, Spain
Interests: molecular nutrition; nutritional and metabolic diseases; adipocytes; hepatocytes; lipogenesis; fat; inflammatory biomarkers; obesity; non-alcoholic fatty liver disease; insulin signaling; insulin; glucose metabolism; lipid metabolism; insulin resistance; adipogenesis; adipose tissue; liver
Special Issues, Collections and Topics in MDPI journals
1. Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy and Lucio Lascaray Research Center, University of the Basque Country (UPV/EHU), Vitoria, Spain
2. CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
3. BIOARABA Institute of Health, Vitoria-Gasteiz, Spain
Interests: obesity; liver steatosis; insulin resistance; bioactive compounds; mitochondria; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The existence of two types of adipose tissue has been described. An important role of white adipose tissue is the storage of triglycerides in the body. In addition, it is an important endocrine organ because it produces a great number of adipokines, which fulfil autocrine, paracrine and endocrine functions. By contrast, the main role of brown adipose tissue is thermogenesis, that is, energy dissipation as heat. It is also able to produce batokines. Thus, both tissues are relevant in obesity development and can be interesting targets for obesity prevention and treatment. Moreover, the browning process of white adipose tissue, described as the appearance of brite adipocytes in white adipose tissue, can be induced by several nutritional situations. In obese subjects, excess adiposity, altered adipokine production and low-grade chronic inflammation are described. Furthermore, alterations in brown adipose tissue activity can be observed.

The aim of this Special Issue focusing on “Nutrition, Brown and White Adipose Tissue” is to provide an in-depth overview of macronutrient, micronutrient and active biomolecule effects, on brown and white adipose tissues, as well as on the browning process. Contributions are welcome in the form of research papers reporting original results or scientific reviews. 

Prof. Dr. María P. Portillo
Dr. Saioa Gómez-Zorita
Guest Editors

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Keywords

  • White adipose tissue
  • Brown adipose tissue
  • Brite adipocytes
  • Browning
  • Obesity
  • Inflammation
  • Adipokines
  • Batokines
  • Nutrients
  • Active biomolecules

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Published Papers (13 papers)

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Research

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14 pages, 2531 KiB  
Article
Regulation of Chemerin and CMKLR1 Expression by Nutritional Status, Postnatal Development, and Gender
by Estrella Sanchez-Rebordelo, Juan Cunarro, Sonia Perez-Sieira, Luisa María Seoane, Carlos Diéguez, Ruben Nogueiras and Sulay Tovar
Int. J. Mol. Sci. 2018, 19(10), 2905; https://doi.org/10.3390/ijms19102905 - 25 Sep 2018
Cited by 10 | Viewed by 3142
Abstract
Chemerin (also known as tazarotene-induced gene 2 and retinoic acid receptor responder 2) has been identified as an adipokine that exerts effects on many biological processes, including adipogenesis, angiogenesis, inflammation, immune responses, and food intake. This variety of effects has led to its [...] Read more.
Chemerin (also known as tazarotene-induced gene 2 and retinoic acid receptor responder 2) has been identified as an adipokine that exerts effects on many biological processes, including adipogenesis, angiogenesis, inflammation, immune responses, and food intake. This variety of effects has led to its implication in obesity and co-morbidities including diabetes and a risk of cardiovascular disease. The biological effects are mostly mediated by a so-called G protein-coupled receptor, chemokine-like receptor 1 (CMKLR1). Given the association of chemerin with obesity and related diseases, we decided to study in detail the regulation of chemerin and CMKLR1 expression in white adipose tissue (WAT). Specifically, we focused on their expression levels in physiological and pathophysiological settings involved in energy balance: e.g., fasting, postnatal development, and gender. We used Sprague Dawley rats with different nutritional statuses, levels of hormonal deficiency, and states of development as well as ob/ob (leptin-deficient) mice. We analysed the protein expression of both the ligand and receptor (chemerin and CMKLR1) in gonadal WAT by western blotting. We found that chemerin and CMKLR1 protein levels were regulated in WAT by different conditions associated with metabolic changes such as nutritional status, sex steroids, pregnancy, and food composition. Our data indicate that regulation of the expression of this new adipokine and its receptor by nutritional status and gonadal hormones may be a part of the adaptive mechanisms related to altered fat mass and its metabolic complications. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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18 pages, 2801 KiB  
Article
Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice
by Christian Carpéné, Saioa Gómez-Zorita, Alice Chaplin and Josep Mercader
Int. J. Mol. Sci. 2018, 19(10), 2904; https://doi.org/10.3390/ijms19102904 - 25 Sep 2018
Cited by 8 | Viewed by 2952
Abstract
Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition [...] Read more.
Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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15 pages, 2642 KiB  
Article
Modulation of Insulin Resistance and the Adipocyte-Skeletal Muscle Cell Cross-Talk by LCn-3PUFA
by Alexandre Pinel, Jean-Paul Rigaudière, Chrystèle Jouve and Frédéric Capel
Int. J. Mol. Sci. 2018, 19(9), 2778; https://doi.org/10.3390/ijms19092778 - 15 Sep 2018
Cited by 9 | Viewed by 4342
Abstract
The cross-talk between skeletal muscle and adipose tissue is involved in the development of insulin resistance (IR) in skeletal muscle, leading to the decrease in the anabolic effect of insulin. We investigated if the long chain polyunsaturated n-3 fatty acids (LCn-3PUFA), eicosapentaenoic and [...] Read more.
The cross-talk between skeletal muscle and adipose tissue is involved in the development of insulin resistance (IR) in skeletal muscle, leading to the decrease in the anabolic effect of insulin. We investigated if the long chain polyunsaturated n-3 fatty acids (LCn-3PUFA), eicosapentaenoic and docosapentaenoic acids (EPA and DPA, respectively) could (1) regulate the development of IR in 3T3-L1 adipocytes and C2C12 muscle cells and (2) inhibit IR in muscle cells exposed to conditioned media (CM) from insulin-resistant adipocytes. Chronic insulin (CI) treatment of adipocytes and palmitic acid (PAL) exposure of myotubes were used to induce IR in the presence, or not, of LCn-3PUFA. EPA (50 µM) and DPA (10 µM) improved PAL-induced IR in myotubes, but had only a partial effect in adipocytes. CM from adipocytes exposed to CI induced IR in C2C12 myotubes. Although DPA increased the mRNA levels of genes involved in fatty acid (FA) beta-oxidation and insulin signaling in adipocytes, it was not sufficient to reduce the secretion of inflammatory cytokines and prevent the induction of IR in myotubes exposed to adipocyte’s CM. Treatment with DPA was able to increase the release of adiponectin by adipocytes into CM. In conclusion, DPA is able to protect myotubes from PAL-induced IR, but not from IR induced by CM from adipocytes. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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14 pages, 3208 KiB  
Article
Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
by Mathew Van de Pette, Simon J. Tunster and Rosalind M. John
Int. J. Mol. Sci. 2018, 19(9), 2734; https://doi.org/10.3390/ijms19092734 - 12 Sep 2018
Cited by 8 | Viewed by 3145
Abstract
Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene with roles in embryonic development, post-natal metabolism and behaviour. Using mouse models with altered dosages of Cdkn1c, we have previously identified a role for the gene in promoting [...] Read more.
Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene with roles in embryonic development, post-natal metabolism and behaviour. Using mouse models with altered dosages of Cdkn1c, we have previously identified a role for the gene in promoting brown adipose tissue formation. Here, we use these transgenic mouse lines to model the loss of imprinting of Cdkn1c in adulthood. We demonstrate that only a two-fold increase in the expression of Cdkn1c during development is sufficient to protect against age-related weight gain in addition to glucose and insulin intolerance. Further to this, we show that the loss of imprinting of Cdkn1c protects against diet-induced obesity. Bisulphite sequencing was performed to test the stability of the two differentially methylated regions that regulate Cdkn1c imprinting, and both were found to be unaltered in aged or diet-challenged adipose tissue, despite drastic reductions in Cdkn1c expression. These data demonstrate a critical role for Cdkn1c in regulating adult adipose tissue, with modest changes in expression capable of protecting against both age and diet-induced obesity and metabolic syndrome, with a natural decline in Cdkn1c expression observed that may contribute to less healthy metabolic aging. Finally, we have observed a post-natal insensitivity of the imprint to environmental factors, in contrast to recent observations of an in utero sensitivity. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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13 pages, 2849 KiB  
Article
Resveratrol and Pterostilbene, Two Analogue Phenolic Compounds, Affect Aquaglyceroporin Expression in a Different Manner in Adipose Tissue
by Saioa Gómez-Zorita, Jenifer Trepiana, Alfredo Fernández-Quintela, Marcela González and María P. Portillo
Int. J. Mol. Sci. 2018, 19(9), 2654; https://doi.org/10.3390/ijms19092654 - 07 Sep 2018
Cited by 6 | Viewed by 3678
Abstract
Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release and glycerol uptake. They are involved in fat metabolism, with implications in obesity. The aim was to determine whether the administration of resveratrol and pterostilbene during the six weeks of the experimental period would [...] Read more.
Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release and glycerol uptake. They are involved in fat metabolism, with implications in obesity. The aim was to determine whether the administration of resveratrol and pterostilbene during the six weeks of the experimental period would modify AQPs expression in white and brown adipose tissues from Wistar rats fed an obesogenic diet, and to establish a potential relationship with the delipidating properties of these compounds. Consequently, thirty-six rats were divided into four groups: (a) group fed a standard diet; and three more groups fed a high-fat high-sucrose diet: (b) high-fat high-sucrose group: (c) pterostilbene-treated group (30 mg/kg/d): (d) resveratrol-treated group (30 mg/kg/d). Epididymal, subcutaneous white adipose tissues and interscapular brown adipose tissue were dissected. AQPs gene expression (RT-PCR) and protein expression (western-blot) were measured. In white adipose tissue, pterostilbene reduced subcutaneous adipose tissue weight and prevented the decrease in AQP9 induced by obesogenic feeding, and thus glycerol uptake for triglyceride accumulation. Resveratrol reduced epididymal adipose tissue weight and avoided the decrease in AQPs related to glycerol release induced by high-fat high-sucrose feeding, suggesting the involvement of lipolysis in its body-fat lowering effect. Regarding brown adipose tissue, AQP7 seemed not to be involved in the previously reported thermogenic activity of both phenolic compounds. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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16 pages, 2833 KiB  
Article
RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis
by Hui-Yu Peng, Yu-Chih Liang, Tse-Hua Tan, Huai-Chia Chuang, Ying-Ju Lin and Jung-Chun Lin
Int. J. Mol. Sci. 2018, 19(9), 2646; https://doi.org/10.3390/ijms19092646 - 06 Sep 2018
Cited by 13 | Viewed by 3440
Abstract
An increase in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) reportedly attenuates insulin-mediated signaling which participates in the development of brown adipose tissues (BATs). Nevertheless, the effect of MAP4K4 on brown adipogenesis remains largely uncharacterized. In this study, results of a transcriptome [...] Read more.
An increase in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) reportedly attenuates insulin-mediated signaling which participates in the development of brown adipose tissues (BATs). Nevertheless, the effect of MAP4K4 on brown adipogenesis remains largely uncharacterized. In this study, results of a transcriptome analysis (also referred as RNA-sequencing) showed differential expressions of MAP4K4 or SRSF3 transcripts isolated from distinct stages of embryonic BATs. The discriminative splicing profiles of MAP4K4 or SRSF3 were noted as well in brown adipocytes (BAs) with RNA-binding motif protein 4-knockout (RBM4−/−) compared to the wild-type counterparts. Moreover, the relatively high expressions of authentic SRSF3 transcripts encoding the splicing factor functioned as a novel regulator toward MAP4K4 splicing during brown adipogenesis. The presence of alternatively spliced MAP4K4 variants exerted differential effects on the phosphorylation of c-Jun N-terminal protein kinase (JNK) which was correlated with the differentiation or metabolic signature of BAs. Collectively, the RBM4-SRSF3-MAP4K4 splicing cascade constitutes a novel molecular mechanism in manipulating the development of BAs through related signaling pathways. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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15 pages, 2679 KiB  
Article
Grape Seed Proanthocyanidins Improve White Adipose Tissue Expansion during Diet-Induced Obesity Development in Rats
by Aïda Pascual-Serrano, Cinta Bladé, Manuel Suárez and Anna Arola-Arnal
Int. J. Mol. Sci. 2018, 19(9), 2632; https://doi.org/10.3390/ijms19092632 - 05 Sep 2018
Cited by 27 | Viewed by 4043
Abstract
The development of metabolic complications associated with obesity has been correlated with a failure of white adipose tissue (WAT) to expand. Our group has previously reported that a 12-week administration of grape seed proanthocyanidin extract (GSPE) together with an obesogenic diet mitigated the [...] Read more.
The development of metabolic complications associated with obesity has been correlated with a failure of white adipose tissue (WAT) to expand. Our group has previously reported that a 12-week administration of grape seed proanthocyanidin extract (GSPE) together with an obesogenic diet mitigated the development of cardiometabolic complications in rats. Using the same cohort of animals, we aim to elucidate whether the prevention of cardiometabolic complications by proanthocyanidins is produced by a healthier expansion of visceral WAT and/or an induction of the browning of WAT. For this, adipocyte size and number in retroperitoneal WAT (rWAT) were determined by histological analyses, and the gene expression levels of markers of adipogenesis, browning, and WAT functionality were quantified by RT-qPCR. The long-term administration of GSPE together with an obesogenic diet expanded rWAT via an increase in the adipocyte number and a preventive decrease in the adipocyte size in a dose-dependent manner. At the molecular level, GSPE seems to induce WAT adipogenesis through the upregulation of peroxisome proliferator-activated receptor (Pparγ) in a Sirtuin 1 (Sirt1)-dependent manner. In conclusion, the healthier visceral WAT expansion induced by proanthocyanidins supplementation may explain the improvement in the cardiometabolic risks associated with obesogenic diets. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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14 pages, 2785 KiB  
Article
Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice
by Eline N. Kuipers, Andrea D. van Dam, Ntsiki M. Held, Isabel M. Mol, Riekelt H. Houtkooper, Patrick C.N. Rensen and Mariëtte R. Boon
Int. J. Mol. Sci. 2018, 19(6), 1786; https://doi.org/10.3390/ijms19061786 - 16 Jun 2018
Cited by 49 | Viewed by 5462
Abstract
Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate [...] Read more.
Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1% w/w) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%, p < 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver Apob expression (−13%, p < 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [3H]oleate, which was derived from glycerol tri[3H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%, p < 0.05). Furthermore, quercetin also markedly increased mRNA expression of Ucp1 (+229%, p < 0.05) and Elovl3 (+138%, p < 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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20 pages, 15526 KiB  
Article
Global Transcriptome Analysis of Brown Adipose Tissue of Diet-Induced Obese Mice
by Jingyi Cao, Qi Zhu, Lin Liu, Bradley J. Glazier, Benjamin C. Hinkel, Chun Liang and Haifei Shi
Int. J. Mol. Sci. 2018, 19(4), 1095; https://doi.org/10.3390/ijms19041095 - 06 Apr 2018
Cited by 16 | Viewed by 6668
Abstract
Consumption of a high-fat diet (HFD) promotes the development of obesity, a disease resulting from an imbalance between energy intake and energy expenditure. Brown adipose tissue (BAT) has thermogenic capacity that burns calories to produce heat, and it is a potential target for [...] Read more.
Consumption of a high-fat diet (HFD) promotes the development of obesity, a disease resulting from an imbalance between energy intake and energy expenditure. Brown adipose tissue (BAT) has thermogenic capacity that burns calories to produce heat, and it is a potential target for the treatment and prevention of obesity. There is limited information regarding the impact of HFD on the BAT transcriptome. We hypothesized that HFD-induced obesity would lead to transcriptional regulation of BAT genes. RNA sequencing was used to generate global transcriptome profiles from BAT of lean mice fed with a low-fat diet (LFD) and obese mice fed with a HFD. Gene Ontology (GO) analysis identified increased expression of genes involved in biological processes (BP) related to immune responses, which enhanced molecular function (MF) in chemokine activity; decreased expression of genes involved in BP related to ion transport and muscle structure development, which reduced MF in channel and transporter activity and structural binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathway analysis indicated that pathways associated with innate immunity were enhanced by HFD, while pathways associated with muscle contraction and calcium signaling were suppressed by HFD. Collectively, these results suggest that diet-induced obesity changes transcriptomic signatures of BAT, leading to dysfunction involving inflammation, calcium signaling, ion transport, and cell structural development. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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Review

Jump to: Research

14 pages, 1600 KiB  
Review
Effects of Polyphenols on Thermogenesis and Mitochondrial Biogenesis
by Tanila Wood dos Santos, Quélita Cristina Pereira, Lucimara Teixeira, Alessandra Gambero, Josep A. Villena and Marcelo Lima Ribeiro
Int. J. Mol. Sci. 2018, 19(9), 2757; https://doi.org/10.3390/ijms19092757 - 13 Sep 2018
Cited by 73 | Viewed by 9676
Abstract
Obesity is a health problem worldwide, and energy imbalance has been pointed out as one of the main factors responsible for its development. As mitochondria are a key element in energy homeostasis, the development of obesity has been strongly associated with mitochondrial imbalance. [...] Read more.
Obesity is a health problem worldwide, and energy imbalance has been pointed out as one of the main factors responsible for its development. As mitochondria are a key element in energy homeostasis, the development of obesity has been strongly associated with mitochondrial imbalance. Polyphenols are the largest group of phytochemicals, widely distributed in the plant kingdom, abundant in fruits and vegetables, and have been classically described as antioxidants owing to their well-established ability to eliminate free radicals and reactive oxygen species (ROS). During the last decade, however, growing evidence reports the ability of polyphenols to perform several important biological activities in addition to their antioxidant activity. Special attention has been given to the ability of polyphenols to modulate mitochondrial processes. Thus, some polyphenols are now recognized as molecules capable of modulating pathways that regulate mitochondrial biogenesis, ATP synthesis, and thermogenesis, among others. The present review reports the main benefits of polyphenols in modulating mitochondrial processes that favor the regulation of energy expenditure and offer benefits in the management of obesity, especially thermogenesis and mitochondrial biogenesis. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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11 pages, 625 KiB  
Review
Role of Cannabinoids in Obesity
by Francesca Rossi, Francesca Punzo, Giuseppina Rosaria Umano, Maura Argenziano and Emanuele Miraglia Del Giudice
Int. J. Mol. Sci. 2018, 19(9), 2690; https://doi.org/10.3390/ijms19092690 - 10 Sep 2018
Cited by 61 | Viewed by 9003
Abstract
Obesity is an increasing health problem worldwide. Its related comorbidities imply a high cost for the National Health System and diminish a patient’s life quality. Adipose tissue is composed of three types of cells. White adipocytes are involved in fat storage and secretion [...] Read more.
Obesity is an increasing health problem worldwide. Its related comorbidities imply a high cost for the National Health System and diminish a patient’s life quality. Adipose tissue is composed of three types of cells. White adipocytes are involved in fat storage and secretion of hormones. Brown adipocytes are involved in thermogenesis and caloric expenditure. Beige adipocytes are transitional adipocytes that in response to various stimuli can turn from white to brown and could be protective against the obesity, enhancing energy expenditure. The conversion of white in beige adipose tissue is a potential new therapeutic target for obesity. Cannabinoid receptors (CB) regulate thermogenesis, food intake and inflammation. CB1 ablation or inhibition helps reducing body weight and food intake. Stimulation of CB2 limits inflammation and promotes anti-obesity effects by reducing food intake and weight gain. Its genetic ablation results in adiposity development. CB receptors are also responsible for transforming white adipose tissue towards beige or brown adipocytes, therefore their modulation can be considered potential anti-obesity target. CB1 principal localization in central nervous system represents an important limit. Stimulation of CB2, principally localized on peripheral cells instead, should facilitate the anti-obesity effects without exerting remarkable psychotropic activity. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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21 pages, 1534 KiB  
Review
p53 Functions in Adipose Tissue Metabolism and Homeostasis
by Jelena Krstic, Isabel Reinisch, Michael Schupp, Tim J. Schulz and Andreas Prokesch
Int. J. Mol. Sci. 2018, 19(9), 2622; https://doi.org/10.3390/ijms19092622 - 04 Sep 2018
Cited by 62 | Viewed by 6884
Abstract
As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms [...] Read more.
As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue- and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53’s impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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38 pages, 1579 KiB  
Review
Regulation of Energy Expenditure and Brown/Beige Thermogenic Activity by Interleukins: New Roles for Old Actors
by María Del Carmen García, Patricia Pazos, Luis Lima and Carlos Diéguez
Int. J. Mol. Sci. 2018, 19(9), 2569; https://doi.org/10.3390/ijms19092569 - 29 Aug 2018
Cited by 15 | Viewed by 5783
Abstract
Obesity rates and the burden of metabolic associated diseases are escalating worldwide Energy burning brown and inducible beige adipocytes in human adipose tissues (ATs) have attracted considerable attention due to their therapeutic potential to counteract the deleterious metabolic effects of nutritional overload and [...] Read more.
Obesity rates and the burden of metabolic associated diseases are escalating worldwide Energy burning brown and inducible beige adipocytes in human adipose tissues (ATs) have attracted considerable attention due to their therapeutic potential to counteract the deleterious metabolic effects of nutritional overload and overweight. Recent research has highlighted the relevance of resident and recruited ATs immune cell populations and their signalling mediators, cytokines, as modulators of the thermogenic activity of brown and beige ATs. In this review, we first provide an overview of the developmental, cellular and functional heterogeneity of the AT organ, as well as reported molecular switches of its heat-producing machinery. We also discuss the key contribution of various interleukins signalling pathways to energy and metabolic homeostasis and their roles in the biogenesis and function of brown and beige adipocytes. Besides local actions, attention is also drawn to their influence in the central nervous system (CNS) networks governing energy expenditure. Full article
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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