Adipocytes and Metabolic Health

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 57166

Special Issue Editor

Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Interests: adipose tissue remodeling; brown fat activation; sympathetic innervation; lipolysis; thermogenesis; energy expenditure
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Special Issue Information

Dear Colleagues,

Over the past decades, emerging evidence has accumulated to support the notion that adipose tissue is not just an inert site for lipid storage. It is also an active endocrine organ, which dynamically secrets multiple adipocyte-derived factors that exert a function on the local- and whole-body metabolism. Furthermore, adipose tissue is actively involved in a complex network of endocrine, paracrine, and autocrine signals, which influence other tissues and organs, including the brain, heart, liver, skeletal muscle, pancreas, and immune system. Adipose tissue has two types—white and brown. The adipocytes in these two types exhibit different a morphology and functions. While the white adipose tissue is the major site to store the lipids and secret adipokines/hormones, the brown adipose tissue is responsible for lipid burning and thermogenesis. During the development of obesity, adipose tissue loses its proper functions. Under the dysfunctional condition, fatty acids, together with other pathological factors, may cause cell stress, local hypoxia, and inflammation, which eventually lead to systemic insulin resistance, the hallmark of type-2 diabetes.

The primary focus of the Special Issue will be focused on a new understanding of adipose tissue biology/pathology, and its central role in the interplay with other tissues and organs. As such, the research articles and/or reviews will explore the mechanisms governing adipose tissue remodelling during obesity, and a potential link between dysfunctional adipose tissue and whole-body metabolic disorders. Findings here will therefore provide novel insights into the signalling pathways that potentially serve as targets to treat obesity and the related metabolic diseases.

Dr. Kai Sun
Guest Editor

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Keywords

  • obesity
  • adipose tissue remodeling
  • energy expenditure
  • lipolysis
  • lipid signaling
  • lipogenesis
  • adipogenesis
  • inflammation
  • insulin resistance

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Published Papers (14 papers)

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Research

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20 pages, 6973 KiB  
Article
Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly
by Alexes C. Daquinag, Zhanguo Gao, Cale Fussell, Kai Sun and Mikhail G. Kolonin
Cells 2020, 9(12), 2646; https://doi.org/10.3390/cells9122646 - 9 Dec 2020
Cited by 11 | Viewed by 3143
Abstract
Proper processing of collagens COL1 and COL6 is required for normal function of adipose tissue and skeletal muscle. Proteoglycan decorin (DCN) regulates collagen fiber formation. The amino-terminus of DCN is modified with an O-linked glycosaminoglycan (GAG), the function of which has remained unclear. [...] Read more.
Proper processing of collagens COL1 and COL6 is required for normal function of adipose tissue and skeletal muscle. Proteoglycan decorin (DCN) regulates collagen fiber formation. The amino-terminus of DCN is modified with an O-linked glycosaminoglycan (GAG), the function of which has remained unclear. Previously, non-glycanated DCN (ngDCN) was identified as a marker of adipose stromal cells. Here, we identify MMP14 as the metalloprotease that cleaves DCN to generate ngDCN. We demonstrate that mice ubiquitously lacking DCN GAG (ngDCN mice) have reduced matrix rigidity, enlarged adipocytes, fragile skin, as well as skeletal muscle hypotrophy, fibrosis, and dysfunction. Our results indicate that DCN deglycanation results in reduced intracellular DCN—collagen binding and increased production of truncated COL6 chains, leading to aberrant procollagen processing and extracellular localization. This study reveals that the GAG of DCN functions to regulate collagen assembly in adipose tissue and skeletal muscle and uncovers a new mechanism of matrix dysfunction in obesity and aging. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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21 pages, 5069 KiB  
Article
Evaluation of Fat Accumulation and Adipokine Production during the Long-Term Adipogenic Differentiation of Porcine Intramuscular Preadipocytes and Study of the Influence of Immunobiotics
by Asuka Tada, AKM Humayun Kober, Md. Aminul Islam, Manami Igata, Michihiro Takagi, Masahiko Suzuki, Hisashi Aso, Wakako Ikeda-Ohtsubo, Kazutoyo Yoda, Kenji Miyazawa, Fang He, Hideki Takahashi, Julio Villena and Haruki Kitazawa
Cells 2020, 9(7), 1715; https://doi.org/10.3390/cells9071715 - 17 Jul 2020
Cited by 3 | Viewed by 2861
Abstract
The degree of fat accumulation and adipokine production are two major indicators of obesity that are correlated with increased adipose tissue mass and chronic inflammatory responses. Adipocytes have been considered effector cells for the inflammatory responses due to their capacity to express Toll-like [...] Read more.
The degree of fat accumulation and adipokine production are two major indicators of obesity that are correlated with increased adipose tissue mass and chronic inflammatory responses. Adipocytes have been considered effector cells for the inflammatory responses due to their capacity to express Toll-like receptors (TLRs). In this study, we evaluated the degree of fat accumulation and adipokine production in porcine intramuscular preadipocyte (PIP) cells maintained for in vitro differentiation over a long period without or with stimulation of either TNF-α or TLR2-, TLR3-, or TLR4-ligands. The cytosolic fat accumulation was measured by liquid chromatography and the expression of adipokines (CCL2, IL-6, IL-8 and IL-10) were quantified by RT-qPCR and ELISA at several time points (0 to 20 days) of PIP cells differentiation. Long-term adipogenic differentiation (LTAD) induced a progressive fat accumulation in the adipocytes over time. Activation of TLR3 and TLR4 resulted in an increased rate of fat accumulation into the adipocytes over the LTAD. The production of CCL2, IL-8 and IL-6 were significantly increased in unstimulated adipocytes during the LTAD, while IL-10 expression remained stable over the studied period. An increasing trend of adiponectin and leptin production was also observed during the LTAD. On the other hand, the stimulation of adipocytes with TLRs agonists or TNF-α resulted in an increasing trend of CCL2, IL-6 and IL-8 production while IL-10 remained stable in all four treatments during the LTAD. We also examined the influences of several immunoregulatory probiotic strains (immunobiotics) on the modulation of the fat accumulation and adipokine production using supernatants of immunobiotic-treated intestinal immune cells and the LTAD of PIP cells. Immunobiotics have shown a strain-specific ability to modulate the fat accumulation and adipokine production, and differentiation of adipocytes. Here, we expanded the utility and potential application of our in vitro PIP cells model by evaluating an LTAD period (20 days) in order to elucidate further insights of chronic inflammatory pathobiology of adipocytes associated with obesity as well as to explore the prospects of immunomodulatory intervention for obesity such as immunobiotics. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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13 pages, 615 KiB  
Article
Increasing the Duration of Light Physical Activity Ameliorates Insulin Resistance Syndrome in Metabolically Healthy Obese Adults
by Fatema Al-Rashed, Abdulwahab Alghaith, Rafaat Azim, Dawood AlMekhled, Reeby Thomas, Sardar Sindhu and Rasheed Ahmad
Cells 2020, 9(5), 1189; https://doi.org/10.3390/cells9051189 - 11 May 2020
Cited by 8 | Viewed by 2414
Abstract
Obesity is a well-known risk factor for insulin resistance syndrome (IRS). Nevertheless, limited data are available regarding the effects of physical activity (PA) intensity on the ability to modulate IRS. The study aim was to investigate the beneficial effects of the longer duration [...] Read more.
Obesity is a well-known risk factor for insulin resistance syndrome (IRS). Nevertheless, limited data are available regarding the effects of physical activity (PA) intensity on the ability to modulate IRS. The study aim was to investigate the beneficial effects of the longer duration of light PA vs. a single bout of the acute moderate or vigorous PA for improvement in IRS indicators. Sixty metabolically healthy obese (MHO) participants, 30 males and 30 females, with body mass index (BMI) of ≥30 were enrolled in this study. PA levels were measured using an accelerometer, and the expression of monocytic surface markers was analyzed using flow cytometry. Plasma cytokines’ secretion was determined by enzyme-linked immunosorbent assay (ELISA). Univariate regression analysis evaluated the actigraphy-assessed PA measures, inflammatory cytokines, and insulin resistance. The longer duration of PA was found to be associated with the homeostatic model assessment of insulin resistance (HOMA-IR), a lower lipid profile, and the expression of inflammatory cytokines by monocytes. Even though, higher intensities of PA were found to be associated with lower body fat percentage, only the light intensity PA was found to be beneficial as it associated with the improved insulin sensitivity and lower expression of inflammatory markers. In conclusion, maintaining the longer duration of low-intensity PA throughout the day could be more beneficial for reducing inflammation and improving insulin resistance. This study supports a more feasible approach model to gain beneficial lifestyle changes for the prevention of IRS in metabolically healthy adults with obesity. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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13 pages, 2906 KiB  
Article
Ecklonia stolonifera Extract Suppresses Lipid Accumulation by Promoting Lipolysis and Adipose Browning in High-Fat Diet-Induced Obese Male Mice
by Heegu Jin, Kippeum Lee, Sungwoo Chei, Hyun-Ji Oh, Kang-Pyo Lee and Boo-Yong Lee
Cells 2020, 9(4), 871; https://doi.org/10.3390/cells9040871 - 2 Apr 2020
Cited by 21 | Viewed by 3596
Abstract
Obesity develops due to an energy imbalance and manifests as the storage of excess triglyceride (TG) in white adipose tissue (WAT). Recent studies have determined that edible natural materials can reduce lipid accumulation and promote browning in WAT. We aimed to determine whether [...] Read more.
Obesity develops due to an energy imbalance and manifests as the storage of excess triglyceride (TG) in white adipose tissue (WAT). Recent studies have determined that edible natural materials can reduce lipid accumulation and promote browning in WAT. We aimed to determine whether Ecklonia stolonifera extract (ESE) would increase the energy expenditure in high-fat diet (HFD)-induced obese mice and 3T3-L1 cells by upregulating lipolysis and browning. ESE is an edible brown marine alga that belongs to the family Laminariaceae and contains dieckol, a phlorotannin. We report that ESE inhibits body mass gain by regulating the expression of proteins involved in adipogenesis and lipogenesis. In addition, ESE activates protein kinase A (PKA) and increases the expression of lipolytic enzymes including adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and monoacylglycerol lipase (MGL) and also thermogenic genes, such as carnitine palmitoyltransferase 1 (CPT1), PR domain-containing 16 (PRDM16), and uncoupling protein 1 (UCP1). These findings indicate that ESE may represent a promising natural means of preventing obesity and obesity-related metabolic diseases. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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20 pages, 3146 KiB  
Article
Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients
by Sardar Sindhu, Shihab Kochumon, Reeby Thomas, Abdullah Bennakhi, Fahd Al-Mulla and Rasheed Ahmad
Cells 2020, 9(3), 730; https://doi.org/10.3390/cells9030730 - 16 Mar 2020
Cited by 25 | Viewed by 3623
Abstract
Interferon regulatory factors (IRFs) are emerging as the metabolic transcriptional regulators in obesity/type-2 diabetes (T2D). IRF5 is implicated with macrophage polarization toward the inflammatory M1-phenotype, nonetheless, changes in the adipose expression of IRF5 in T2D and relationship of these changes with other markers [...] Read more.
Interferon regulatory factors (IRFs) are emerging as the metabolic transcriptional regulators in obesity/type-2 diabetes (T2D). IRF5 is implicated with macrophage polarization toward the inflammatory M1-phenotype, nonetheless, changes in the adipose expression of IRF5 in T2D and relationship of these changes with other markers of adipose inflammation remain unclear. Therefore, we determined the IRF5 gene expression in subcutaneous adipose tissue samples from 46 T2D patients including 35 obese (Body Mass Index/BMI 33.83 ± 0.42 kg/m2) and 11 lean/overweight individuals (BMI 27.55 ± 0.46 kg/m2) using real-time qRT-PCR. IRF5 protein expression was assessed using immunohistochemistry and confocal microscopy. Fasting plasma glucose, insulin, HbA1c, C-reactive protein, cholesterol, low- and high-density lipoproteins (LDL/HDL), and triglycerides were measured using commercial kits. IRF5 gene expression was compared with that of signature inflammatory markers and several clinico-metabolic indicators. The data (mean ± SEM) show the enhanced adipose IRF5 gene (p = 0.03) and protein (p = 0.05) expression in obese compared to lean/overweight diabetic patients. Adipose IRF5 transcripts in diabetic obese individuals associated positively with those of TNF-α, IL-18, IL-23A, CXCL8, CCL2, CCL7, CCR1/5, CD11c, CD68, CD86, TLR4/7/10, Dectin-1, FGL-2, MyD88, NF-κB, IRF3, and AML1 (p < 0.05). In diabetic lean/overweight subjects, IRF5 expression associated with BMI, body fat %age, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR, C-reactive protein (CRP), IL-5, and IL-1RL1 expression; while in all T2D patients, IRF5 expression correlated with that of IRF4, TLR2/8, and CD163. In conclusion, upregulated adipose tissue IRF5 expression in diabetic obese patients concurs with the inflammatory signatures and it may represent a potential marker for metabolic inflammation in obesity/T2D. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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19 pages, 3620 KiB  
Article
Effect of Dietary Silk Peptide on Obesity, Hyperglycemia, and Skeletal Muscle Regeneration in High-Fat Diet-Fed Mice
by Kippeum Lee, Heegu Jin, Sungwoo Chei, Hyun-Ji Oh, Jeong-Yong Lee and Boo-Yong Lee
Cells 2020, 9(2), 377; https://doi.org/10.3390/cells9020377 - 6 Feb 2020
Cited by 19 | Viewed by 4632
Abstract
Obesity is associated with excess body fat accumulation that can cause hyperglycemia and reduce skeletal muscle function and strength, which characterize the development of sarcopenic obesity. In this study, we aimed to determine the mechanism whereby acid-hydrolyzed silk peptide (SP) prevents high-fat diet [...] Read more.
Obesity is associated with excess body fat accumulation that can cause hyperglycemia and reduce skeletal muscle function and strength, which characterize the development of sarcopenic obesity. In this study, we aimed to determine the mechanism whereby acid-hydrolyzed silk peptide (SP) prevents high-fat diet (HFD)-induced obesity and whether it regulates glucose uptake and muscle differentiation using in vivo and in vitro approaches. Our findings demonstrate that SP inhibits body mass gain and the expression of adipogenic transcription factors in visceral adipose tissue (VAT). SP also had an anti-diabetic effect in VAT and skeletal muscle because it upregulated glucose transporter type 4 (GLUT4) and uncoupling protein 3 (UCP3) expression. Furthermore, SP reduced ubiquitin proteasome and promoted myoblast determination protein 1 (MyoD)/myogenic factor 4 (myogenin) expression, implying that it may have potential for the treatment of obesity-induced hyperglycemia and obesity-associated sarcopenia. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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15 pages, 6818 KiB  
Article
A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion
by Xin Wang, Min Liu, Guo He Cai, Yan Chen, Xiao Chen Shi, Cong Cong Zhang, Bo Xia, Bao Cai Xie, Huan Liu, Rui Xin Zhang, Jun Feng Lu, Meng Qing Zhu, Shi Zhen Yang, Xin Yi Chu, Dan Yang Zhang, Yong Liang Wang and Jiang Wei Wu
Cells 2020, 9(2), 331; https://doi.org/10.3390/cells9020331 - 31 Jan 2020
Cited by 23 | Viewed by 3475
Abstract
The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays [...] Read more.
The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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30 pages, 11566 KiB  
Article
Comprehensive Analysis of the Characteristics and Differences in Adult and Newborn Brown Adipose Tissue (BAT): Newborn BAT Is a More Active/Dynamic BAT
by Junyu Liu, Chuanhai Zhang, Boyang Zhang, Yao Sheng, Wentao Xu, Yunbo Luo, Xiaoyun He and Kunlun Huang
Cells 2020, 9(1), 201; https://doi.org/10.3390/cells9010201 - 14 Jan 2020
Cited by 10 | Viewed by 3947
Abstract
Brown adipose tissue (BAT) plays an essential role in maintaining body temperature and in treating obesity and diabetes. The adult BAT (aBAT) and neonatal BAT (neBAT) vary greatly in capacity, but the characteristics and differences between them on the molecular level, as well [...] Read more.
Brown adipose tissue (BAT) plays an essential role in maintaining body temperature and in treating obesity and diabetes. The adult BAT (aBAT) and neonatal BAT (neBAT) vary greatly in capacity, but the characteristics and differences between them on the molecular level, as well as the related features of BAT as it develops post-delivery, have not yet been fully determined. In this study, we examined the morphological features of aBAT and neBAT of mice by using hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We found that neBAT contains a smaller number and size of lipid droplets, as well as more abundant mitochondria, compared with aBAT. The dynamic morphological changes revealed that the number and size of lipid droplets increase, but the number of mitochondria gradually decrease during the post-delivery development, which consisted of some differences in RNA or protein expression levels, such as gradually decreased uncoupling protein 1 (UCP1) expression levels and mitochondrial genes, such as mitochondrial transcription factor A (Tfam). The adipocyte differentiation-related genes, such as transcription factor CCAAT enhancer-binding protein β (CEBPβ), were also continuously upregulated. Additionally, the different features of aBAT and neBAT were analyzed from the global transcription (RNA-Seq) level, which included messenger RNA (mRNA), microRNA, long non-coding RNA (lncRNA), circRNA, and DNA methylation, as well as proteins (proteomics). Differentially methylated region (DMR) analysis identified 383 hyper- and 503 hypo-methylated genes, as well as 1221 new circRNA in ne-BAT and 1991 new circRNA in a-BAT, with significantly higher expression of circRNA in aBAT compared with neBAT. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that mitochondrial activity, protein synthesis, and cell life activity levels were higher in neBAT, and pathways related to ribosomes, spliceosomes, and metabolism were significantly activated in neBAT compared to aBAT. Collectively, this study describes the dynamic changes occurring throughout post-delivery development from the morphological, molecular and omics perspectives. Our study provides information that may be utilized in improving BAT functional activity through gene regulation and/or epigenetic regulation. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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14 pages, 3008 KiB  
Article
Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression
by Dong Uk Im, Sang Chon Kim, Gia Cac Chau and Sung Hee Um
Cells 2019, 8(11), 1460; https://doi.org/10.3390/cells8111460 - 18 Nov 2019
Cited by 20 | Viewed by 4714
Abstract
Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of [...] Read more.
Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear. Here, we show that carbamazepine increased the expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and fatty acid synthase (FASN) in 3T3-L1 cells. Notably, carbamazepine inhibited the expression levels of β-catenin, a negative regulator of adipogenesis, leading to enhanced adipogenesis. Conversely, β-catenin overexpression abolished the effect of carbamazepine on adipogenic gene expression. However, depletion of β-catenin further enhanced PPARγ expression. In addition, carbamazepine reduced β-catenin expression by lowering the levels of phospho-low density lipoprotein receptor-related protein 6 (p-LRP6) and phospho-glycogen synthase kinase 3β (p-GSK3β) in Wnt/β-catenin signaling. Moreover, carbamazepine reduced Wnt mRNA expression and decreased the promoter activities of TCF, the target of β-catenin during adipogenesis. These results suggest that carbamazepine enhances adipogenesis by suppressing Wnt/β-catenin expression, indicating its potential effects on obesity-related metabolism. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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22 pages, 5439 KiB  
Article
Increased Adipose Tissue Expression of Interferon Regulatory Factor (IRF)-5 in Obesity: Association with Metabolic Inflammation
by Sardar Sindhu, Reeby Thomas, Shihab Kochumon, Ajit Wilson, Mohamed Abu-Farha, Abdullah Bennakhi, Fahd Al-Mulla and Rasheed Ahmad
Cells 2019, 8(11), 1418; https://doi.org/10.3390/cells8111418 - 11 Nov 2019
Cited by 24 | Viewed by 4266
Abstract
Interferon regulatory factor (IRF)-5 is known to be involved in M1 macrophage polarization, however, changes in the adipose expression of IRF5 in obesity and their relationship with the local expression of proinflammatory cytokines/chemokines are unknown. Therefore, IRF5 gene expression was determined in the [...] Read more.
Interferon regulatory factor (IRF)-5 is known to be involved in M1 macrophage polarization, however, changes in the adipose expression of IRF5 in obesity and their relationship with the local expression of proinflammatory cytokines/chemokines are unknown. Therefore, IRF5 gene expression was determined in the subcutaneous adipose tissue samples from 53 non-diabetic individuals (6 lean, 18 overweight, and 29 obese), using real-time RT-PCR. IRF5 protein expression was also assessed using immunohistochemistry and/or confocal microscopy. Adipose gene expression of signature immune metabolic markers was also determined and compared with adipose IRF5 gene expression. Systemic levels of C-reactive protein and adiponectin were measured by ELISA. The data show that adipose IRF5 gene (P = 0.008) and protein (P = 0.004) expression was upregulated in obese compared with lean individuals. IRF5 expression changes correlated positively with body mass index (BMI; r = 0.37/P = 0.008) and body fat percentage (r = 0.51/P = 0.0004). In obese, IRF5 changes associated positively with HbA1c (r = 0.41/P = 0.02). A good agreement was found between gene and protein expression of IRF5 in obese subjects (r = 0.65/P = 0.001). IRF5 gene expression associated positively with adipose inflammatory signatures including local expression of TNF-α, IL-6, CXCL8, CCL-2/5, IL-1β, IL-18, CXCL-9/10, CCL7, CCR-1/2/5, TLR-2/7/8/9, IRF3, MyD88, IRAK-1, and inflammatory macrophage markers (P < 0.05). Interestingly, IRF5 gene expression correlated positively with CRP (r = 0.37, P = 0.03) and negatively with adiponectin levels (r = −0.43, P = 0.009). In conclusion, elevated adipose IRF5 expression in obesity concurs with the typical inflammatory signatures, locally and systemically. Hence, the IRF5 upregulation may represent a novel adipose tissue marker for metabolic inflammation. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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15 pages, 1676 KiB  
Article
Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin
by Irina AlKhairi, Preethi Cherian, Mohamed Abu-Farha, Ashraf Al Madhoun, Rasheeba Nizam, Motasem Melhem, Mohamed Jamal, Suleiman Al-Sabah, Hamad Ali, Jaakko Tuomilehto, Fahd Al-Mulla and Jehad Abubaker
Cells 2019, 8(10), 1283; https://doi.org/10.3390/cells8101283 - 19 Oct 2019
Cited by 52 | Viewed by 5153
Abstract
Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the [...] Read more.
Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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11 pages, 1540 KiB  
Article
Potential Roles of Adiponectin Isoforms in Human Obesity with Delayed Wound Healing
by Jiyoon Ryu, Colleen A. Loza, Huan Xu, Min Zhou, Jason T. Hadley, Jielei Wu, Huayu You, Huaiqing Wang, Jihong Yang, Juli Bai, Feng Liu, Christie Bialowas and Lily Q. Dong
Cells 2019, 8(10), 1134; https://doi.org/10.3390/cells8101134 - 24 Sep 2019
Cited by 12 | Viewed by 3224
Abstract
Adiponectin is an adipokine with anti-insulin resistance and anti-inflammatory functions. It exists in serum predominantly in three multimeric complexes: the trimer, hexamer, and high-molecular-weight forms. Although recent studies indicate that adiponectin promotes wound healing in rodents, its role in the wound healing process [...] Read more.
Adiponectin is an adipokine with anti-insulin resistance and anti-inflammatory functions. It exists in serum predominantly in three multimeric complexes: the trimer, hexamer, and high-molecular-weight forms. Although recent studies indicate that adiponectin promotes wound healing in rodents, its role in the wound healing process in humans is unknown. This study investigated the expression levels of adiponectin in adipose tissue and serum of women who experienced either normal or delayed wound healing after abdominal plastic surgery. We found that obese women with delayed healing had slightly lower total adiponectin levels in their adipose tissue compared with women with normal healing rates. Among the different isoforms of adiponectin, levels of the trimer forms were significantly reduced in adipose tissue, but not the serum, of obese women with delayed healing compared to women who healed normally. This study provides clinical evidence for a potential role of low-molecular-weight oligomers of adiponectin in the wound healing process as well as implications for an autocrine and/or paracrine mechanism of adiponectin action in adipose tissues. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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Review

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25 pages, 2501 KiB  
Review
Adipose Stromal Cell Expansion and Exhaustion: Mechanisms and Consequences
by Kristin Eckel-Mahan, Aleix Ribas Latre and Mikhail G. Kolonin
Cells 2020, 9(4), 863; https://doi.org/10.3390/cells9040863 - 2 Apr 2020
Cited by 27 | Viewed by 6525
Abstract
Adipose tissue (AT) is comprised of a diverse number of cell types, including adipocytes, stromal cells, endothelial cells, and infiltrating leukocytes. Adipose stromal cells (ASCs) are a mixed population containing adipose progenitor cells (APCs) as well as fibro-inflammatory precursors and cells supporting the [...] Read more.
Adipose tissue (AT) is comprised of a diverse number of cell types, including adipocytes, stromal cells, endothelial cells, and infiltrating leukocytes. Adipose stromal cells (ASCs) are a mixed population containing adipose progenitor cells (APCs) as well as fibro-inflammatory precursors and cells supporting the vasculature. There is growing evidence that the ability of ASCs to renew and undergo adipogenesis into new, healthy adipocytes is a hallmark of healthy fat, preventing disease-inducing adipocyte hypertrophy and the spillover of lipids into other organs, such as the liver and muscles. However, there is building evidence indicating that the ability for ASCs to self-renew is not infinite. With rates of ASC proliferation and adipogenesis tightly controlled by diet and the circadian clock, the capacity to maintain healthy AT via the generation of new, healthy adipocytes appears to be tightly regulated. Here, we review the contributions of ASCs to the maintenance of distinct adipocyte pools as well as pathogenic fibroblasts in cancer and fibrosis. We also discuss aging and diet-induced obesity as factors that might lead to ASC senescence, and the consequences for metabolic health. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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16 pages, 1911 KiB  
Review
Towards a Better Understanding of Beige Adipocyte Plasticity
by Esther Paulo and Biao Wang
Cells 2019, 8(12), 1552; https://doi.org/10.3390/cells8121552 - 1 Dec 2019
Cited by 33 | Viewed by 4655
Abstract
Beige adipocytes are defined as Ucp1+, multilocular adipocytes within white adipose tissue (WAT) that are capable of thermogenesis, the process of heat generation. In both mouse models and humans, the increase of beige adipocyte population, also called WAT browning, is associated [...] Read more.
Beige adipocytes are defined as Ucp1+, multilocular adipocytes within white adipose tissue (WAT) that are capable of thermogenesis, the process of heat generation. In both mouse models and humans, the increase of beige adipocyte population, also called WAT browning, is associated with certain metabolic benefits, such as reduced obesity and increased insulin sensitivity. In this review, we summarize the current knowledge regarding WAT browning, with a special focus on the beige adipocyte plasticity, collectively referring to a bidirectional transition between thermogenic active and latent states in response to environmental changes. We further exploit the utility of a unique beige adipocyte ablation system to interrogate anti-obesity effect of beige adipocytes in vivo. Full article
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
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