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Molecular Regulation of Exercise on Adipose Tissue and Related Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 29184

Special Issue Editor


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Guest Editor
Graduate School of Health and Sports Science, Doshisha University, 1–3 Tatara-Miyakodani, Kyoto 610–0394, Japan
Interests: exercise biology/biochemistry; adipose tissue biology; obesity; insulin resistance; metabolic syndrome/diabetes; adipokines; energy homeostasis; signal transduction; G protein-coupled receptors; oxidative stress; inflammation; stem cell; pancreatic beta cell function; endothelial function; ageing; cardiology; hypertension

Special Issue Information

Dear Colleagues, 

Excess expansion of visceral adipose tissue, accompanied by lower vascularity, increased lipid content of adipocytes, dysregulated adipokines, and dysfunction of adipogenesis, causes the development of metabolic syndrome with adipose tissue hypoxia and inflammation. Therefore, control of the quantity and quality of adipose tissue is essential for the maintenance of “healthy adipose tissue” without metabolic disturbance. In this context, habitual exercise is known to reduce fat mass and ameliorate several inflammation-related events. Growing evidence suggests that habitual exercise results in the beiging of subcutaneous adipose tissue in rodents and affects the differentiation potency of adipose tissue-derived stem cells. Nonetheless, the molecular mechanisms underlying habitual exercise-induced healthy adipose tissue remain unclear. This Special Issue, “Molecular Regulation of Exercise on Adipose Tissue and Related Diseases”, welcomes both original papers and review articles addressing updates on molecular and cellular targets of exercise to improve dysfunction of adipose tissue, which comprises various cell types. New insights into the mechanisms by which exercise can manage diseases linked to obesity are particularly welcome.

Prof. Tetsuya Izawa
Guest Editor

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Published Papers (8 papers)

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Research

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21 pages, 4953 KiB  
Article
Physical Activity Attenuates the Obesity-Induced Dysregulated Expression of Brown Adipokines in Murine Interscapular Brown Adipose Tissue
by Takuya Sakurai, Toshiyuki Fukutomi, Sachiko Yamamoto, Eriko Nozaki and Takako Kizaki
Int. J. Mol. Sci. 2021, 22(19), 10391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910391 - 27 Sep 2021
Cited by 2 | Viewed by 1924
Abstract
In recent years, brown adipose tissue (BAT), which has a high heat-producing capacity, has been confirmed to exist even in adults, and it has become a focal point for the prevention and the improvement of obesity and lifestyle-related diseases. However, the influences of [...] Read more.
In recent years, brown adipose tissue (BAT), which has a high heat-producing capacity, has been confirmed to exist even in adults, and it has become a focal point for the prevention and the improvement of obesity and lifestyle-related diseases. However, the influences of obesity and physical activity (PA) on the fluid factors secreted from BAT (brown adipokines) are not well understood. In this study, therefore, we focused on brown adipokines and investigated the effects of obesity and PA. The abnormal expressions of gene fluid factors such as galectin-3 (Lgals3) and Lgals3 binding protein (Lgals3bp), whose proteins are secreted from HB2 brown adipocytes, were observed in the interscapular BAT of obese mice fed a high-fat diet for 4 months. PA attenuated the abnormalities in the expressions of these genes. Furthermore, although the gene expressions of factors related to brown adipocyte differentiation such as peroxisome proliferator-activated receptor gamma coactivator 1-α were also down-regulated in the BAT of the obese mice, PA suppressed the down-regulation of these factors. On the other hand, lipogenesis was increased more in HB2 cells overexpressing Lgals3 compared with that in control cells, and the overexpression of Lgals3bp decreased the mitochondrial mass. These results indicate that PA attenuates the obesity-induced dysregulated expression of brown adipokines and suggests that Lgals3 and Lgals3bp are involved in brown adipocyte differentiation. Full article
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12 pages, 3603 KiB  
Article
Protective Effects of Voluntary Exercise on Hepatic Fat Accumulation Induced by Dietary Restriction in Zucker Fatty Rats
by Yuka Kurosaka, Shuichi Machida, Yoko Shiroya, Hideki Yamauchi and Kumiko Minato
Int. J. Mol. Sci. 2021, 22(4), 2014; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042014 - 18 Feb 2021
Cited by 2 | Viewed by 2214
Abstract
Weight control based on dietary restriction (DR) alone can cause lipid metabolic failure and progression to fatty liver. This study aimed to investigate the effect of exercise on preventing DR-induced hepatic fat accumulation in Zucker fatty (ZF) rats by focusing on the relationship [...] Read more.
Weight control based on dietary restriction (DR) alone can cause lipid metabolic failure and progression to fatty liver. This study aimed to investigate the effect of exercise on preventing DR-induced hepatic fat accumulation in Zucker fatty (ZF) rats by focusing on the relationship between adipose tissue lipolysis and hepatic fat uptake. Six-week-old male ZF rats were randomly assigned to obese, DR, or DR with exercise (DR + Ex) groups. The DR and DR + Ex groups were fed a restricted diet, with the latter also undergoing voluntary exercise. After 6 weeks, hepatic fat accumulation was observed in the DR group, whereas intrahepatic fat was markedly reduced in the DR + Ex group. Compared with the obese (Ob) group, the DR group exhibited 2.09-fold expression of hepatic fatty acid translocase (FAT)/CD36 proteins (p < 0.01) and 0.14-fold expression of hepatic fatty acid-binding protein (FABP)1 (p < 0.01). There were no significant differences between the DR + Ex group and the Ob group. FAT/CD36 and hepatic triglyceride (TG) expression levels were strongly positively correlated (r = 0.81, p < 0.001), whereas there was a strong negative correlation between FABP1 and hepatic TG expression levels (r = −0.65, p < 0.001). Our results suggest that hepatic fat accumulation induced by DR in ZF rats might be prevented through exercise-induced modifications in FAT/CD36 and FABP1 expression. Full article
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21 pages, 4712 KiB  
Article
Metabolomic Profiles in Adipocytes Differentiated from Adipose-Derived Stem Cells Following Exercise Training or High-Fat Diet
by Seita Osawa, Hisashi Kato, Yuki Maeda, Hisashi Takakura, Junetsu Ogasawara and Tetsuya Izawa
Int. J. Mol. Sci. 2021, 22(2), 966; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020966 - 19 Jan 2021
Cited by 2 | Viewed by 3131
Abstract
Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of [...] Read more.
Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of ADSCs-derived adipocytes. The rats were divided into four groups: normal diet (ND)-fed control (ND-SED), ND-fed TR (ND-TR), HFD-fed control (HFD-SED), and HFD-fed TR (HFD-TR). After 9 weeks of intervention, ADSCs of epididymal and inguinal adipose tissues were differentiated into adipocytes. In the metabolome analysis of adipocytes after isoproterenol stimulation, 116 metabolites were detected. The principal component analysis demonstrated that ADSCs-derived adipocytes segregated into four clusters in each fat pad. Amino acid accumulation was greater in epididymal ADSCs-derived adipocytes of ND-TR and HFD-TR, but lower in inguinal ADSCs-derived adipocytes of ND-TR, than in the respective controls. HFD accumulated several metabolites including amino acids in inguinal ADSCs-derived adipocytes and more other metabolites in epididymal ones. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that TR mainly affected the pathways related to amino acid metabolism, except in inguinal ADSCs-derived adipocytes of HFD-TR rats. These findings provide a new way to understand the mechanisms underlying possible changes in the differentiation of ADSCs due to TR or HFD. Full article
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11 pages, 1812 KiB  
Article
The Effects of Continuous and Withdrawal Voluntary Wheel Running Exercise on the Expression of Senescence-Related Genes in the Visceral Adipose Tissue of Young Mice
by Masaki Kimura, Seiya Suzuki, Atsushi Moriya, Kazuki Nogami, Ryoei Uchida, Yoshimasa Saito and Hidetsugu Saito
Int. J. Mol. Sci. 2021, 22(1), 264; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010264 - 29 Dec 2020
Cited by 6 | Viewed by 2167
Abstract
Obesity has become a global medical problem. The upregulation of senescence-related markers in adipose tissue may cause impairment of adipose tissue and disorders of systemic metabolism. Weight control through diet has been found to ameliorate senescence in the adipose tissue. Exercise is also [...] Read more.
Obesity has become a global medical problem. The upregulation of senescence-related markers in adipose tissue may cause impairment of adipose tissue and disorders of systemic metabolism. Weight control through diet has been found to ameliorate senescence in the adipose tissue. Exercise is also important in maintaining a healthy lifestyle, however, very few researchers have examined the relationship between senescence-related markers in adipose tissue. Dietary restriction is also reported to have a legacy effect, wherein the effects are maintained for some periods after the termination of the intervention. However, very few researchers have examined the relationship between exercise and senescence-related markers in adipose tissue. Besides, there is no study on the long-term effects of exercise. Hence, we investigated whether the exercise could change the expression of senescence-related genes in the visceral adipose tissue of young mice and whether there was a legacy effect of exercise for 10 weeks after the termination of exercise. Four-week-old male ICR mice were assigned to one of the three groups: 20 weeks of sedentary condition, 20 weeks of voluntary wheel running exercise, or 10 weeks of exercise followed by 10 weeks of sedentary condition. The mice showed decreased expression in genes related to senescence and senescence-associated secretory phenotype, such as p53, p16, and IL-6, in the visceral adipose tissue in response to exercise. These effects were maintained for 10 weeks after the mice stopped exercising. Our study is the first report that exercise reduces the expression of senescence-related genes in the visceral adipose tissue of young mice, and that exercise causes the legacy effect. Full article
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18 pages, 1962 KiB  
Article
Exercise Training-Enhanced Lipolytic Potency to Catecholamine Depends on the Time of the Day
by Hisashi Kato, Junetsu Ogasawara, Hisashi Takakura, Ken Shirato, Takuya Sakurai, Takako Kizaki and Tetsuya Izawa
Int. J. Mol. Sci. 2020, 21(18), 6920; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186920 - 21 Sep 2020
Cited by 7 | Viewed by 3216
Abstract
Exercise training is well known to enhance adipocyte lipolysis in response to hormone challenge. However, the existence of a relationship between the timing of exercise training and its effect on adipocyte lipolysis is unknown. To clarify this issue, Wistar rats were run on [...] Read more.
Exercise training is well known to enhance adipocyte lipolysis in response to hormone challenge. However, the existence of a relationship between the timing of exercise training and its effect on adipocyte lipolysis is unknown. To clarify this issue, Wistar rats were run on a treadmill for 9 weeks in either the early part (E-EX) or late part of the active phase (L-EX). L-EX rats exhibited greater isoproterenol-stimulated lipolysis expressed as fold induction over basal lipolysis, with greater protein expression levels of hormone-sensitive lipase (HSL) phosphorylated at Ser 660 compared to E-EX rats. Furthermore, we discovered that Brain and muscle Arnt-like (BMAL)1 protein can associate directly with several protein kinase A (PKA) regulatory units (RIα, RIβ, and RIIβ) of protein kinase, its anchoring protein (AKAP)150, and HSL, and that the association of BMAL1 with the regulatory subunits of PKA, AKAP150, and HSL was greater in L-EX than in E-EX rats. In contrast, comparison between E-EX and their counterpart sedentary control rats showed a greater co-immunoprecipitation only between BMAL1 and ATGL. Thus, both E-EX and L-EX showed an enhanced lipolytic response to isoproterenol, but the mechanisms underlying exercise training-enhanced lipolytic response to isoproterenol were different in each group. Full article
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Review

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21 pages, 860 KiB  
Review
Skeletal Muscle–Adipose Tissue–Tumor Axis: Molecular Mechanisms Linking Exercise Training in Prostate Cancer
by Sílvia Rocha-Rodrigues, Andreia Matos, José Afonso, Miguel Mendes-Ferreira, Eduardo Abade, Eduardo Teixeira, Bruno Silva, Eugenia Murawska-Ciałowicz, Maria José Oliveira and Ricardo Ribeiro
Int. J. Mol. Sci. 2021, 22(9), 4469; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094469 - 25 Apr 2021
Cited by 5 | Viewed by 4615
Abstract
Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. [...] Read more.
Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. Exercise training (ET) induces several adaptations in both skeletal muscle and WAT. Some of these effects are mediated by ET-induced synthesis and secretion of several proteins, known as myo- and adipokines. Together, myokines and adipokines may act in an endocrine-like manner to favor communication between skeletal muscle and WAT, as they may work together to improve whole-body metabolic health. This crosstalk may constitute a potential mechanism by which ET exerts its beneficial role in the prevention and treatment of PCa-related disorders; however, this has not yet been explored. Therefore, we reviewed the current evidence on the effects of skeletal muscle–WAT–tumor crosstalk in PCa, and the potential mediators of this process to provide a better understanding of underlying ET-related mechanisms in cancer. Full article
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23 pages, 1212 KiB  
Review
Endurance Exercise Mitigates Immunometabolic Adipose Tissue Disturbances in Cancer and Obesity
by José Cesar Rosa-Neto and Loreana Sanches Silveira
Int. J. Mol. Sci. 2020, 21(24), 9745; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249745 - 21 Dec 2020
Cited by 6 | Viewed by 5507
Abstract
Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation [...] Read more.
Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation by adipocytokines secretion. The interactions between metabolic active tissues and immune cells, called immunometabolism, is an important field for discovering new pathways and approaches to treat immunometabolic diseases, such as obesity and cancer. Moreover, physical exercise is widely known as a tool for prevention and adjuvant treatment on metabolic diseases. More specifically, aerobic exercise training is able to increase the energy expenditure, reduce the nutrition overload and modify the profile of adipocytokines and myokines with paracrine and endocrine effects. Therefore, our aim in this review was to cover the effects of aerobic exercise training on the immunometabolism of adipose tissue in obesity and cancer, focusing on the exercise-related modification on adipose tissue or immune cells isolated as well as their interaction. Full article
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17 pages, 1155 KiB  
Review
Functional Mechanisms of Mitochondrial Respiratory Chain Supercomplex Assembly Factors and Their Involvement in Muscle Quality
by Kotaro Azuma, Kazuhiro Ikeda and Satoshi Inoue
Int. J. Mol. Sci. 2020, 21(9), 3182; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093182 - 30 Apr 2020
Cited by 28 | Viewed by 5819
Abstract
Impairment of skeletal muscle function causes disabilities in elderly people. Therefore, in an aged society, prevention and treatment of sarcopenia are important for expanding healthy life expectancy. In addition to aging, adipose tissue disfunction and inflammation also contribute to the pathogenesis of sarcopenia [...] Read more.
Impairment of skeletal muscle function causes disabilities in elderly people. Therefore, in an aged society, prevention and treatment of sarcopenia are important for expanding healthy life expectancy. In addition to aging, adipose tissue disfunction and inflammation also contribute to the pathogenesis of sarcopenia by causing the combined state called ‘sarcopenic obesity’. Muscle quality as well as muscle mass contributes to muscle strength and physical performance. Mitochondria in the skeletal muscles affect muscle quality by regulating the production of energy and reactive oxygen species. A certain portion of the mitochondrial respiratory chain complexes form a higher-order structure called a “supercomplex”, which plays important roles in efficient energy production, stabilization of respiratory chain complex I, and prevention of reactive oxygen species (ROS) generation. Several molecules including phospholipids, proteins, and certain chemicals are known to promote or stabilize mitochondrial respiratory chain supercomplex assembly directly or indirectly. In this article, we review the distinct mechanisms underlying the promotion or stabilization of mitochondrial respiratory chain supercomplex assembly by supercomplex assembly factors. Further, we introduce regulatory pathways of mitochondrial respiratory chain supercomplex assembly and discuss the roles of supercomplex assembly factors and regulatory pathways in skeletal muscles and adipose tissues, believing that this will lead to discovery of potential targets for prevention and treatment of muscle disorders such as sarcopenia. Full article
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