scholarly journals Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities

2020 ◽  
Vol 12 (2) ◽  
pp. 85-101
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

2021 ◽  
Vol 14 (1) ◽  
pp. 153-161
Author(s):  
Deepika Sharma ◽  
Swati Sharma ◽  
Preeti Chauhan

Obesity is due to imbalance between energy intake and energy expenditure. Adipose tissues are the main site for the fat storage as well as for dissipation. There are two types of adipose tissues: white adipose tissue, which store fat as triglyceride, brown adipose tissue, which burns the fat into energy through the thermogenesis due to uncoupling protein1 present in inner mitochondrial membrane. Histone acylation causes changes in the chromatin structure without causing any change in the deoxyribonucleic acidsequence and thus regulate gene expression.Histonedeacetylase causes the deacylation of histone and interfere with function of histone. Thus histonedeacetylase inhibitors alter the expression of thermogenic gene encoding uncoupling protein 1, peroxisome proliferator activated receptor γ and also causes browning or beiging of white adipose tissue and increases the energy expenditure.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 831 ◽  
Author(s):  
Virag Vas ◽  
Tamás Háhner ◽  
Gyöngyi Kudlik ◽  
Dávid Ernszt ◽  
Krisztián Kvell ◽  
...  

Obesity and adipocyte malfunction are related to and arise as consequences of disturbances in signaling pathways. Tyrosine kinase substrate with four Src homology 3 domains (Tks4) is a scaffold protein that establishes a platform for signaling cascade molecules during podosome formation and epidermal growth factor receptor (EGFR) signaling. Several lines of evidence have also suggested that Tks4 has a role in adipocyte biology; however, its roles in the various types of adipocytes at the cellular level and in transcriptional regulation have not been studied. Therefore, we hypothesized that Tks4 functions as an organizing molecule in signaling networks that regulate adipocyte homeostasis. Our aims were to study the white and brown adipose depots of Tks4 knockout (KO) mice using immunohistology and western blotting and to analyze gene expression changes regulated by the white, brown, and beige adipocyte-related transcription factors via a PCR array. Based on morphological differences in the Tks4-KO adipocytes and increased uncoupling protein 1 (UCP1) expression in the white adipose tissue (WAT) of Tks4-KO mice, we concluded that the beigeing process was more robust in the WAT of Tks4-KO mice compared to the wild-type animals. Furthermore, in the Tks4-KO WAT, the expression profile of peroxisome proliferator-activated receptor gamma (PPARγ)-regulated adipogenesis-related genes was shifted in favor of the appearance of beige-like cells. These results suggest that Tks4 and its downstream signaling partners are novel regulators of adipocyte functions and PPARγ-directed white to beige adipose tissue conversion.


Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Shoba Shetty ◽  
Maria A. Ramos-Roman ◽  
You-Ree Cho ◽  
Jonathan Brown ◽  
Jorge Plutzky ◽  
...  

Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here, we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 ± 1.5 vs. 25.3 ± 6.8 mg/kg · min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1α, and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism.


2006 ◽  
Vol 27 (3) ◽  
pp. 282-294 ◽  
Author(s):  
P. Christopher LaRosa ◽  
Jess Miner ◽  
Yuannan Xia ◽  
You Zhou ◽  
Steve Kachman ◽  
...  

A combined histological and microarray analysis of the white adipose tissue (WAT) of mice fed trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) was performed to better define functional responses. Mice fed t10c12 CLA for 14 days lost 85% of WAT mass, 95% of adipocyte lipid droplet volume, and 15 or 47% of the number of adipocytes and total cells, respectively. Microarray profiling of replicated pools ( n = 2 per day × diet) of control and treated mice ( n = 140) at seven time points after 1–17 days of t10c12 CLA feeding found between 2,682 and 4,216 transcript levels changed by twofold or more. Transcript levels for genes involved in glucose and fatty acid import or biosynthesis were significantly reduced. Highly expressed transcripts for lipases were significantly reduced but still abundant. Increased levels of mRNAs for two key thermogenesis proteins, uncoupling protein 1 and carnitine palmitoyltransferase 1, may have increased energy expenditures. Significant reductions of mRNAs for major adipocyte regulatory factors, including peroxisome proliferator activated receptor-γ, sterol regulatory binding protein 1, CAAT/enhancer binding protein-α, and lipin 1 were correlated with the reduced transcript levels for key metabolic pathways in the WAT. A prolific inflammation response was indicated by the 2- to 100-fold induction of many cytokine transcripts, including those for IL-6, IL-1β, TNF ligands, and CXC family members, and an increased density of macrophages. The mRNA changes suggest that a combination of cell loss, increased energy expenditure, and residual transport of lipids out of the adipocytes may account for the cumulative mass loss observed.


Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5954
Author(s):  
Kyeong Jo Kim ◽  
Eui-Seon Jeong ◽  
Ki Hoon Lee ◽  
Ju-Ryun Na ◽  
Soyi Park ◽  
...  

Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.


2018 ◽  
Vol 61 (3) ◽  
pp. 115-126 ◽  
Author(s):  
Jessica A Deis ◽  
Hong Guo ◽  
Yingjie Wu ◽  
Chengyu Liu ◽  
David A Bernlohr ◽  
...  

Lipocalin-2 (LCN2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for LCN2 in the recruitment and retinoic acid-induced activation of brown-like or ‘beige’ adipocytes. We found LCN2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived from Lcn2 −/− mice. Lcn2 −/− inguinal adipocytes have attenuated insulin-induced upregulation of thermogenic gene expression and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway activation. This is accompanied by a lower basal and maximal oxidative capacity in Lcn2 −/− inguinal adipocytes, indicating mitochondrial dysfunction. Recombinant Lcn2 was able to restore insulin-induced p38MAPK phosphorylation in both WT and Lcn2 −/− inguinal adipocytes. Rosiglitazone treatment during differentiation of Lcn2 −/− adipocytes is able to recruit beige adipocytes at a normal level, however, further activation of beige adipocytes by insulin and RA is impaired in the absence of LCN2. Further, the synergistic effect of insulin and RA on UCP1 and PGC-1α expression is markedly reduced in Lcn2 −/− inguinal adipocytes. Most intriguingly, LCN2 and the retinoic acid receptor-alpha (RAR-α) are concurrently translocated to the plasma membrane of adipocytes in response to insulin, and this insulin-induced RAR-α translocation is absent in adipocytes deficient in LCN2. Our data suggest a novel LCN2-mediated pathway by which RA and insulin synergistically regulates activation of beige adipocytes via a non-genomic pathway of RA action.


2002 ◽  
Vol 282 (1) ◽  
pp. R114-R121 ◽  
Author(s):  
Gregory E. Demas ◽  
Robert R. Bowers ◽  
Timothy J. Bartness ◽  
Thomas W. Gettys

Siberian hamsters exhibit seasonal fluctuations in white adipose tissue (WAT) mass, with peaks in long “summerlike” days (LDs) and nadirs in short “winterlike” days (SDs). These responses can be mimicked in the laboratory after transfer from LDs to SDs. The purpose of the present study was to test whether changes in WAT and brown adipose tissue (BAT) gene expression that are mediated by the sympathetic nervous system in other obesity models are also associated with seasonal adiposity changes in Siberian hamsters. SDs decreased WAT mass and leptin mRNA, increased WAT β3-adrenoceptor mRNA, and induced retroperitoneal WAT uncoupling protein-1 mRNA (the latter measured by RT-PCR, others measured by ribonuclease protection assay) while increasing BAT uncoupling protein-1 and peroxisome proliferator-activated receptor-γ coactivator-1 mRNAs. These effects were not due to SD-induced gonadal regression and largely occurred before the usual SD-induced decreases in food intake. Thus the SD-induced decreased adiposity of Siberian hamsters may be due to a coordinated suite of WAT and BAT gene transcription changes ultimately increasing lipid mobilization and utilization.


Author(s):  
Chang-Hyung Lee ◽  
Young-A Choi ◽  
Sung-Jin Heo ◽  
Parkyong Song

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


2020 ◽  
Author(s):  
Pardis Irandoost ◽  
Naimeh Mesri Alamdari ◽  
Atoosa Saidpour ◽  
Farzad Shidfar ◽  
Neda Roshanravan ◽  
...  

Abstract Background: Obesity is a public health problem across the world. Development of beige adipocytes in white adipose tissue (WAT) and activation of brown adipose tissue (BAT) can support obesity management. We aimed to investigate the effects of royal jelly (RJ) and tocotrienol-rich fraction (TRF) along with calorie restriction diet (CRD) on the genes involved in beige fat formation and BAT activation.Methods: Fifty 3-week-old male Wistar rats were fed high-fat diet (HFD) for 17 weeks. When obesity was induced, they were randomly divided into 5 groups (n=10/group): HFD, CRD, RJ+CRD, TRF+CRD, RJ+TRF+CRD for an additional 8 weeks. Finally, body weight was measured. Moreover, WAT and BAT were dissected for assessing the expression of major genes involved in adipose thermogenesis and histological changes evaluation. Results: At the end of the intervention, weight significantly decreased in RJ and RJ+TRF groups relative to the CRD group (p<0.05). RJ remarkably increased the expression of uncoupling protein 1 (UCP1) by 5.81 and 4.99 times more than CRD alone in WAT and BAT respectively (p<0.001). Expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), peroxisome proliferator-activated receptor-α (PPAR-α) and Sirtuin1 (SIRT1) was significantly increased in WAT and BAT of rats receiving RJ and RJ+TRF. Peroxisome proliferator-activated receptor-γ (PPAR-Ƴ) expression was not noticeably changed in assessed adipose tissues. Brown-like adipocytes in WAT and denser adipocytes in BAT were obvious in RJ and RJ+TRF groups. However, the effect of TRF on studied genes was not noticeable. Conclusion: RJ+CRD improved markers of adipose thermogenesis and induced anti-obesity effects more than CRD alone did. Furthermore, RJ remodeled adipose tissue and could be considered as a new therapeutic target.


2019 ◽  
Vol 317 (6) ◽  
pp. E1140-E1149 ◽  
Author(s):  
Yasuhiro Kawabe ◽  
Jun Mori ◽  
Hidechika Morimoto ◽  
Mihoko Yamaguchi ◽  
Satoshi Miyagaki ◽  
...  

The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1–7 (Ang 1–7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1–7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg−1·day−1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1–7 axis represent a potential therapeutic approach to prevent the development of obesity.


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