International Journal of Molecular Sciences

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18 pages, 3833 KiB

Open AccessArticle

Oxygenated Water Inhibits Adipogenesis and Attenuates Hepatic Steatosis in High-Fat Diet-Induced Obese Mice

by Yuh-Jen Cheng, Chao-Chi Liu, Fang-Yeh Chu, Ching-Ping Yang, Chiao-Wan Hsiao, Cheng-Wei Chuang, Ming-Yuh Shiau, Hsueh-Te Lee, Jen-Ning Tsai and Yih-Hsin Chang

Int. J. Mol. Sci. 2020, 21(15), 5493; https://doi.org/10.3390/ijms21155493 - 31 Jul 2020

Cited by 1 | Viewed by 2901

Abstract

The expansion of adipose tissue mass is the primary characteristic of the process of becoming obesity, which causes chronic adipose inflammation and is closely associated with type 2 diabetes mellitus (T2DM). Adipocyte hypertrophy restricts oxygen availability, leading to microenvironmental hypoxia and adipose dysfunction. [...] Read more.

The expansion of adipose tissue mass is the primary characteristic of the process of becoming obesity, which causes chronic adipose inflammation and is closely associated with type 2 diabetes mellitus (T2DM). Adipocyte hypertrophy restricts oxygen availability, leading to microenvironmental hypoxia and adipose dysfunction. This study aimed at investigating the effects of oxygenated water (OW) on adipocyte differentiation (adipogenesis) and the metabolic function of mature adipocytes. The effects of OW on adipogenesis and the metabolic function of mature adipocytes were examined. Meanwhile, the in vivo metabolic effects of long-term OW consumption on diet-induced obesity (DIO) mice were investigated. OW inhibited adipogenesis and lipid accumulation through down-regulating critical adipogenic transcription factors and lipogenic enzymes. While body weight, blood and adipose parameters were not significantly improved by long-term OW consumption, transient circulatory triglyceride-lowering and glucose tolerance-improving effects were identified. Notably, hepatic lipid contents were significantly reduced, indicating that the DIO-induced hepatic steatosis was attenuated, despite no improvements in fibrosis and lipid contents in adipose tissue being observed in the OW-drinking DIO mice. The study provides evidence regarding OW’s effects on adipogenesis and mature adipocytes, and the corresponding molecular mechanisms. OW exhibits transient triglyceride-lowering and glucose tolerance-improving activity as well as hepatic steatosis-attenuating functions. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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17 pages, 2878 KiB

Open AccessArticle

The Expression Profile of Dental Pulp-Derived Stromal Cells Supports Their Limited Capacity to Differentiate into Adipogenic Cells

by Letícia Fracaro, Alexandra C. Senegaglia, Roberto H. Herai, Amanda Leitolis, Lidiane M. Boldrini-Leite, Carmen L. K. Rebelatto, Paul J. Travers, Paulo R. S. Brofman and Alejandro Correa

Int. J. Mol. Sci. 2020, 21(8), 2753; https://doi.org/10.3390/ijms21082753 - 15 Apr 2020

Cited by 17 | Viewed by 3622

Abstract

Mesenchymal stromal cells (MSCs) can self-renew, differentiate into specialised cells and have different embryonic origins—ectodermal for dental pulp-derived MSCs (DPSCs) and mesodermal for adipose tissue-derived MSCs (ADSCs). Data on DPSCs adipogenic differentiation potential and timing vary, and the lack of molecular and genetic [...] Read more.

Mesenchymal stromal cells (MSCs) can self-renew, differentiate into specialised cells and have different embryonic origins—ectodermal for dental pulp-derived MSCs (DPSCs) and mesodermal for adipose tissue-derived MSCs (ADSCs). Data on DPSCs adipogenic differentiation potential and timing vary, and the lack of molecular and genetic information prompted us to gain a better understanding of DPSCs adipogenic differentiation potential and gene expression profile. While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). To better understand this limitation in adipogenesis, transcriptome analysis in undifferentiated DPSCs was carried out, with the ADSC transcriptome used as a positive control. In total, 14,871 transcripts were common to DPSCs and ADSCs, some were unique (DPSCs: 471, ADSCs: 1032), and 510 were differentially expressed genes. Detailed analyses of overrepresented transcripts showed that DPSCs express genes that inhibit adipogenic differentiation, revealing the possible mechanism for their limited adipogenesis. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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20 pages, 2258 KiB

Open AccessArticle

Lipid Deposition and Mobilisation in Atlantic Salmon Adipocytes

by Marta Bou, Xinxia Wang, Marijana Todorčević, Tone-Kari Knutsdatter Østbye, Jacob Torgersen and Bente Ruyter

Int. J. Mol. Sci. 2020, 21(7), 2332; https://doi.org/10.3390/ijms21072332 - 27 Mar 2020

Cited by 9 | Viewed by 5682

Abstract

The present study aimed to elucidate how Atlantic salmon adipocytes pre-enriched with palmitic (16:0, PA), oleic (18:1n−9, OA), or eicosapentaenoic (20:5n−3, EPA) acid respond to a fasting condition mimicked by nutrient deprivation and glucagon. All experimental groups were supplemented [...] Read more.

The present study aimed to elucidate how Atlantic salmon adipocytes pre-enriched with palmitic (16:0, PA), oleic (18:1n−9, OA), or eicosapentaenoic (20:5n−3, EPA) acid respond to a fasting condition mimicked by nutrient deprivation and glucagon. All experimental groups were supplemented with radiolabeled PA to trace secreted lipids and distribution of radioactivity in different lipid classes. There was a higher content of intracellular lipid droplets in adipocytes pre-enriched with OA than in adipocytes pre-enriched with PA or EPA. In the EPA group, the radiolabeled PA was mainly esterified in phospholipids and triacylglycerols, whereas in the OA and PA groups, the radioactivity was mainly recovered in phospholipids and cholesterol-ester. By subjecting the experimental groups to nutrient-deprived media supplemented with glucagon, lipolysis occurred in all groups, although to a lower extent in the OA group. The lipids were mainly secreted as esterified lipids in triacylglycerols and phospholipids, indicating mobilization in lipoproteins. A significant proportion was secreted as free fatty acids and glycerol. Leptin secretion was reduced in all experimental groups in response to fasting, while the mitochondria area responded to changes in the energy supply and demand by increasing after 3 h of fasting. Overall, different lipid classes in adipocytes influenced their mobilization during fasting. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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16 pages, 1565 KiB

Open AccessArticle

Soluble Epoxide Hydrolase 2 Expression Is Elevated in Obese Humans and Decreased by Physical Activity

by Abdelkrim Khadir, Sina Kavalakatt, Dhanya Madhu, Preethi Cherian, Fahd Al-Mulla, Jehad Abubaker and Ali Tiss

Int. J. Mol. Sci. 2020, 21(6), 2056; https://doi.org/10.3390/ijms21062056 - 17 Mar 2020

Cited by 12 | Viewed by 3321

Abstract

Epoxide hydrolase 2 (EPHX2) is an emerging therapeutic target in several immunometabolic disorders. EPHX2 metabolizes anti-inflammatory epoxyeicosatrienoic acids into pro-inflammatory diols. The contribution of EPHX2 activity to human obesity remains unexplored. We compared the expression of EPHX2 between lean and obese humans ( [...] Read more.

Epoxide hydrolase 2 (EPHX2) is an emerging therapeutic target in several immunometabolic disorders. EPHX2 metabolizes anti-inflammatory epoxyeicosatrienoic acids into pro-inflammatory diols. The contribution of EPHX2 activity to human obesity remains unexplored. We compared the expression of EPHX2 between lean and obese humans (n = 20 each) in subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs) using RT-PCR, Western Blot analysis, immunohistochemistry, and confocal microscopy before and after a 3-month physical activity regimen. We also assessed EPHX2 levels during preadipocyte differentiation in humans and mice. EPHX2 mRNA and protein expression were significantly elevated in obese subjects, with concomitant elevated endoplasmic reticulum (ER) stress components (the 78-kDa glucose-regulated protein; GRP78, and the Activating transcription factor 6; ATF6) and inflammatory markers (Tumor necrosis factor-α; TNFα, and Interleukin 6; IL6) as compared to controls (p < 0.05). EPHX2 mRNA levels strongly correlated with adiposity markers. In obese individuals, physical activity attenuated EPHX2 expression levels in both the SAT and PBMCs, with a parallel decrease in ER stress and inflammation markers. EPHX2 expression was also elevated during differentiation of both human primary and 3T3-L1 mouse preadipocytes. Mediators of cellular stress (palmitate, homocysteine, and macrophage culture medium) also increased EPHX2 expression in 3T3-L1 preadipocytes. Our findings suggest that EPHX2 upregulation is linked to ER stress in adiposity and that physical activity may attenuate metabolic stress by reducing EPHX2 expression. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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20 pages, 7112 KiB

Open AccessArticle

Short-Term Responses to Fatty Acids on Lipid Metabolism and Adipogenesis in Rainbow Trout (Oncorhynchus mykiss)

by Natàlia Riera-Heredia, Esmail Lutfi, Albert Sánchez-Moya, Joaquim Gutiérrez, Encarnación Capilla and Isabel Navarro

Int. J. Mol. Sci. 2020, 21(5), 1623; https://doi.org/10.3390/ijms21051623 - 27 Feb 2020

Cited by 11 | Viewed by 4251

Abstract

Fish are rich in n-3 long-chain polyunsaturated fatty acids (LC-PUFA) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Due to the increasing use of vegetable oils (VO), their proportion in diets has lowered, affecting lipid metabolism and fillet composition. Rainbow trout cultured preadipocytes [...] Read more.

Fish are rich in n-3 long-chain polyunsaturated fatty acids (LC-PUFA) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Due to the increasing use of vegetable oils (VO), their proportion in diets has lowered, affecting lipid metabolism and fillet composition. Rainbow trout cultured preadipocytes were treated with representative FA found in fish oils (EPA and DHA) or VO (linoleic, LA and alpha-linolenic, ALA acids), while EPA and LA were also orally administered, to evaluate their effects on adipogenesis and lipid metabolism. In vitro, all FA increased lipid internalization, with ALA producing the highest effect, together with upregulating the FA transporter fatp1. In vivo, EPA or LA increased peroxisome proliferator-activated receptors ppara and pparb transcripts abundance in adipose tissue, suggesting elevated β-oxidation, contrary to the results obtained in liver. Furthermore, the increased expression of FA synthase (fas) and the FA translocase/cluster of differentiation (cd36) in adipose tissue indicated an enhanced uptake of lipids and lipogenesis de novo, whereas stable or low hepatic expression of genes involved in lipid transport and turnover was found. Thus, fish showed a similar tissue metabolic response to the short-term availability of EPA or LA in vivo, while in vitro VO-derived FA demonstrated greater potential inducing fat accumulation. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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20 pages, 4332 KiB

Open AccessArticle

Age- and BMI-Associated Expression of Angiogenic Factors in White Adipose Tissue of Children

by Niklas Gaebler, Benedikt Haggenmüller, Melanie Kapapa, Alexandre Serra, Daniel Tews, Jan-Bernd Funcke, Stephanie Brandt, Valentin Ioannidis, Michael Schön, Peter Möller, Klaus-Michael Debatin, Martin Wabitsch and Pamela Fischer-Posovszky

Int. J. Mol. Sci. 2019, 20(20), 5204; https://doi.org/10.3390/ijms20205204 - 21 Oct 2019

Cited by 8 | Viewed by 3372

Abstract

The growth of adipose tissue and its vasculature are tightly associated. Angiogenic factors have been linked to obesity, yet little is known about their expression during early childhood. To identify associations of angiogenic factors with characteristics on individual and tissue level, subcutaneous white [...] Read more.

The growth of adipose tissue and its vasculature are tightly associated. Angiogenic factors have been linked to obesity, yet little is known about their expression during early childhood. To identify associations of angiogenic factors with characteristics on individual and tissue level, subcutaneous white adipose tissue samples were taken from 45 children aged 0–9 years undergoing elective surgery. We measured the expression of vascular endothelial growth factor A (VEFGA), fibroblast growth factor 1 and 2 (FGF1, FGF2), angiopoietin 1 and 2 (ANGPT1, ANGPT2), TEK receptor tyrosine kinase (TEK), and von Willebrand factor (VWF). In addition, we determined the mean adipocyte size in histologic tissue sections. We found positive correlations of age with FGF1 and FGF2 and a negative correlation with ANGPT2, with pronounced differences in the first two years of life. FGF1, FGF2, and ANGPT1 correlated positively with adipocyte size. Furthermore, we identified a correlation of ANGPT1 and TEK with body mass index-standard deviation score (BMI-SDS), a measure to define childhood obesity. Except for ANGPT2, all angiogenic factors correlated positively with the endothelial marker VWF. In sum, our findings suggest that differences related to BMI-SDS begin early in childhood, and the analyzed angiogenic factors possess distinct roles in adipose tissue biology. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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11 pages, 1547 KiB

Open AccessArticle

Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies

by Nicholas Wilson, Robert Steadman, Ilaria Muller, Mohd Draman, D. Aled Rees, Peter Taylor, Colin M. Dayan, Marian Ludgate and Lei Zhang

Int. J. Mol. Sci. 2019, 20(11), 2675; https://doi.org/10.3390/ijms20112675 - 31 May 2019

Cited by 5 | Viewed by 3702

Abstract

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have [...] Read more.

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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12 pages, 1975 KiB

Open AccessCommunication

Exercise Rescues Gene Pathways Involved in Vascular Expansion and Promotes Functional Angiogenesis in Subcutaneous White Adipose Tissue

by So Yun Min, Heather Learnard, Shashi Kant, Olga Gealikman, Raziel Rojas-Rodriguez, Tiffany DeSouza, Anand Desai, John F. Keaney, Jr., Silvia Corvera and Siobhan M. Craige

Int. J. Mol. Sci. 2019, 20(8), 2046; https://doi.org/10.3390/ijms20082046 - 25 Apr 2019

Cited by 19 | Viewed by 4293

Abstract

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose [...] Read more.

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect. Similarly, angiogenic capacity as measured by ex vivo capillary sprouting was significantly promoted with exercise. Together, these data demonstrate that exercise enhances scWAT vascularization and functional capacity for angiogenesis, and can prevent the detrimental effects of HFD. The improvement in these indices correlates with improvement of whole-body metabolism, suggesting that scWAT vascularization may be a potential therapeutic target for metabolic disease. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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Review

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22 pages, 1405 KiB

Open AccessReview

NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

by Kelvin Ka-Lok Wu, Samson Wing-Ming Cheung and Kenneth King-Yip Cheng

Int. J. Mol. Sci. 2020, 21(11), 4184; https://doi.org/10.3390/ijms21114184 - 11 Jun 2020

Cited by 52 | Viewed by 8040

Abstract

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade [...] Read more.

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade chronic inflammation and excessive immune cell infiltration, is a hallmark of obesity, as well as an important link to cardiometabolic diseases. Amongst the pro-inflammatory factors secreted by the dysfunctional adipose tissue, interleukin (IL)-1β, induced by the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, not only impairs peripheral insulin sensitivity, but it also interferes with the endocrine and immune functions of adipose tissue in a paracrine manner. Human studies indicated that NLRP3 activity in adipose tissues positively correlates with obesity and its metabolic complications, and treatment with the IL-1β antibody improves glycaemia control in type 2 diabetic patients. In mouse models, genetic or pharmacological inhibition of NLRP3 activation pathways or IL-1β prevents adipose tissue dysfunction, including inflammation, fibrosis, defective lipid handling and adipogenesis, which in turn alleviates obesity and its related metabolic disorders. In this review, we summarize both the negative and positive regulators of NLRP3 inflammasome activation, and its pathophysiological consequences on immunometabolism. We also discuss the potential therapeutic approaches to targeting adipose tissue inflammasome for the treatment of obesity and its related metabolic disorders. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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32 pages, 2726 KiB

Open AccessReview

Adipose Tissue Modification through Feeding Strategies and Their Implication on Adipogenesis and Adipose Tissue Metabolism in Ruminants

by Olaia Urrutia, José Antonio Mendizabal, Leopoldo Alfonso, Beatriz Soret, Kizkitza Insausti and Ana Arana

Int. J. Mol. Sci. 2020, 21(9), 3183; https://doi.org/10.3390/ijms21093183 - 30 Apr 2020

Cited by 29 | Viewed by 5704

Abstract

Dietary recommendations by health authorities have been advising of the importance of diminishing saturated fatty acids (SFA) consumption and replacing them by polyunsaturated fatty acids (PUFA), particularly omega-3. Therefore, there have been efforts to enhance food fatty acid profiles, helping them to meet [...] Read more.

Dietary recommendations by health authorities have been advising of the importance of diminishing saturated fatty acids (SFA) consumption and replacing them by polyunsaturated fatty acids (PUFA), particularly omega-3. Therefore, there have been efforts to enhance food fatty acid profiles, helping them to meet human nutritional recommendations. Ruminant meat is the major dietary conjugated linoleic acid (CLA) source, but it also contains SFA at relatively high proportions, deriving from ruminal biohydrogenation of PUFA. Additionally, lipid metabolism in ruminants may differ from other species. Recent research has aimed to modify the fatty acid profile of meat, and other animal products. This review summarizes dietary strategies based on the n-3 PUFA supplementation of ruminant diets and their effects on meat fatty acid composition. Additionally, the role of n-3 PUFA in adipose tissue (AT) development and in the expression of key genes involved in adipogenesis and lipid metabolism is discussed. It has been demonstrated that linseed supplementation leads to an increase in α-linolenic acid (ALA) and eicosapentaenoic acid (EPA), but not in docosahexaenoic acid (DHA), whilst fish oil and algae increase DHA content. Dietary PUFA can alter AT adiposity and modulate lipid metabolism genes expression, although further research is required to clarify the underlying mechanism. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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23 pages, 1285 KiB

Open AccessReview

Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets

by Nerea Gandoy-Fieiras, Jose Ramon Gonzalez-Juanatey and Sonia Eiras

Int. J. Mol. Sci. 2020, 21(7), 2641; https://doi.org/10.3390/ijms21072641 - 10 Apr 2020

Cited by 26 | Viewed by 5343

Abstract

The main energy substrate of adult cardiomyocytes for their contractility are the fatty acids. Its metabolism generates high ATP levels at the expense of high oxygen consumption in the mitochondria. Under low oxygen supply, they can get energy from other substrates, mainly glucose, [...] Read more.

The main energy substrate of adult cardiomyocytes for their contractility are the fatty acids. Its metabolism generates high ATP levels at the expense of high oxygen consumption in the mitochondria. Under low oxygen supply, they can get energy from other substrates, mainly glucose, lactate, ketone bodies, etc., but the mitochondrial dysfunction, in pathological conditions, reduces the oxidative metabolism. In consequence, fatty acids are stored into epicardial fat and its accumulation provokes inflammation, insulin resistance, and oxidative stress, which enhance the myocardium dysfunction. Some therapies focused on improvement the fatty acids entry into mitochondria have failed to demonstrate benefits on cardiovascular disorders. Oppositely, those therapies with effects on epicardial fat volume and inflammation might improve the oxidative metabolism of myocardium and might reduce the cardiovascular disease progression. This review aims at explain (a) the energy substrate adaptation of myocardium in physiological conditions, (b) the reduction of oxidative metabolism in pathological conditions and consequences on epicardial fat accumulation and insulin resistance, and (c) the reduction of cardiovascular outcomes after regulation by some therapies. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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27 pages, 872 KiB

Open AccessReview

Adipogenesis: A Necessary but Harmful Strategy

by Mohammed El Hafidi, Mabel Buelna-Chontal, Fausto Sánchez-Muñoz and Roxana Carbó

Int. J. Mol. Sci. 2019, 20(15), 3657; https://doi.org/10.3390/ijms20153657 - 26 Jul 2019

Cited by 51 | Viewed by 9327

Abstract

Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological process, necessary to sequester lipids effectively to avoid lipotoxicity in other tissues, like the liver, heart, muscle, essential for [...] Read more.

Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological process, necessary to sequester lipids effectively to avoid lipotoxicity in other tissues, like the liver, heart, muscle, essential for maintaining metabolic homeostasis and has a crucial role as a component of the innate immune system, far beyond than only being an inert mass of energy storage. In pathophysiological conditions, adipogenesis promotes a pro-inflammatory state, angiogenesis and the release of adipokines, which become dangerous to health. It results in a hypoxic state, causing oxidative stress and the synthesis and release of harmful free fatty acids. In this review, we try to explain the mechanisms occurring at the breaking point, at which adipogenesis leads to an uncontrolled lipotoxicity. This review highlights the types of adipose tissue and their functions, their way of storing lipids until a critical point, which is associated with hypoxia, inflammation, insulin resistance as well as lipodystrophy and adipogenesis modulation by Krüppel-like factors and miRNAs. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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14 pages, 696 KiB

Open AccessReview

Anti-Obesity Effects of Dietary Calcium: The Evidence and Possible Mechanisms

by Fenglin Zhang, Jingjing Ye, Xiaotong Zhu, Lina Wang, Ping Gao, Gang Shu, Qingyan Jiang and Songbo Wang

Int. J. Mol. Sci. 2019, 20(12), 3072; https://doi.org/10.3390/ijms20123072 - 23 Jun 2019

Cited by 59 | Viewed by 11386

Abstract

Obesity is a serious health challenge worldwide and is associated with various comorbidities, including dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing effective strategies to prevent obesity is therefore of paramount importance. One potential strategy to reduce obesity is to consume calcium, which [...] Read more.

Obesity is a serious health challenge worldwide and is associated with various comorbidities, including dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing effective strategies to prevent obesity is therefore of paramount importance. One potential strategy to reduce obesity is to consume calcium, which has been implicated to be involved in reducing body weight/fat. In this review, we compile the evidence for the anti-obesity roles of calcium in cells, animals, and humans. In addition, we summarize the possible anti-obesity mechanisms of calcium, including regulation of (a) adipogenesis, (b) fat metabolism, (c) adipocyte (precursor) proliferation and apoptosis, (d) thermogenesis, (e) fat absorption and excretion, and (f) gut microbiota. Although the exact anti-obesity roles of calcium in different subjects and how calcium induces the proposed anti-obesity mechanisms need to be further investigated, the current evidence demonstrates the anti-obesity effects of calcium and suggests the potential application of dietary calcium for prevention of obesity. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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18 pages, 1615 KiB

Open AccessReview

High Fructose Intake and Adipogenesis

by Adrián Hernández-Díazcouder, Rodrigo Romero-Nava, Roxana Carbó, L. Gabriela Sánchez-Lozada and Fausto Sánchez-Muñoz

Int. J. Mol. Sci. 2019, 20(11), 2787; https://doi.org/10.3390/ijms20112787 - 7 Jun 2019

Cited by 47 | Viewed by 12378

Abstract

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The [...] Read more.

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues. Several tissues including adipose tissue express the main fructose transporter GLUT5. In vivo, chronic fructose intake promotes white adipose tissue accumulation through activating adipogenesis. In vitro experiments have also demonstrated that fructose alone induces adipogenesis by several mechanisms, including (1) triglycerides and very-low-density lipoprotein (VLDL) production by fructose metabolism, (2) the stimulation of glucocorticoid activation by increasing 11β-HSD1 activity, and (3) the promotion of reactive oxygen species (ROS) production through uric acid, NOX and XOR expression, mTORC1 signaling and Ang II induction. Moreover, it has been observed that fructose induces adipogenesis through increased ACE2 expression, which promotes high Ang-(1-7) levels, and through the inhibition of the thermogenic program by regulating Sirt1 and UCP1. Finally, microRNAs may also be involved in regulating adipogenesis in high fructose intake conditions. In this paper, we propose further directions for research in fructose participation in adipogenesis. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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22 pages, 1866 KiB

Open AccessReview

Neuroendocrine Regulation of Energy Metabolism Involving Different Types of Adipose Tissues

by Qi Zhu, Bradley J. Glazier, Benjamin C. Hinkel, Jingyi Cao, Lin Liu, Chun Liang and Haifei Shi

Int. J. Mol. Sci. 2019, 20(11), 2707; https://doi.org/10.3390/ijms20112707 - 1 Jun 2019

Cited by 45 | Viewed by 10694

Abstract

Despite tremendous research efforts to identify regulatory factors that control energy metabolism, the prevalence of obesity has been continuously rising, with nearly 40% of US adults being obese. Interactions between secretory factors from adipose tissues and the nervous system innervating adipose tissues play [...] Read more.

Despite tremendous research efforts to identify regulatory factors that control energy metabolism, the prevalence of obesity has been continuously rising, with nearly 40% of US adults being obese. Interactions between secretory factors from adipose tissues and the nervous system innervating adipose tissues play key roles in maintaining energy metabolism and promoting survival in response to metabolic challenges. It is currently accepted that there are three types of adipose tissues, white (WAT), brown (BAT), and beige (BeAT), all of which play essential roles in maintaining energy homeostasis. WAT mainly stores energy under positive energy balance, while it releases fuels under negative energy balance. Thermogenic BAT and BeAT dissipate energy as heat under cold exposure to maintain body temperature. Adipose tissues require neural and endocrine communication with the brain. A number of WAT adipokines and BAT batokines interact with the neural circuits extending from the brain to cooperatively regulate whole-body lipid metabolism and energy homeostasis. We review neuroanatomical, histological, genetic, and pharmacological studies in neuroendocrine regulation of adipose function, including lipid storage and mobilization of WAT, non-shivering thermogenesis of BAT, and browning of BeAT. Recent whole-tissue imaging and transcriptome analysis of differential gene expression in WAT and BAT yield promising findings to better understand the interaction between secretory factors and neural circuits, which represents a novel opportunity to tackle obesity. Full article

(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)

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