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Peripheral Targets in Obesity: Pathologies and Therapeutics

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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 (31 August 2020) | Viewed by 20544

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Special Issue Editor

Dr. Deanne H. Hryciw

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Guest Editor

School of Environment and Sciences, Griffith University, Nathan, QLD 4111, Australia
Interests: endocannabinoid system; development; cell signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity is a significant social and financial burden, in developed and developing countries. Alarmingly, the incidence of obesity is increasing significantly worldwide, in both adults and children. Of concern, obesity and its associated pathologies (including but not limited to Type 2 Diabetes Mellitus (T2DM), kidney disease and cardiovascular disease) increase morbidity and mortality and reduce the quality of life irrespective of age, sex, or culture. Obesity often is the result of a disparity between nutritional intake, energy expenditure, and energy storage. Emerging research in the area of pathophysiology, associated with obesity, has identified a clear role for the periphery in the maintenance of the obese state. Furthermore, the periphery plays a significant role in the link between obesity and complex diseases such as T2DM, kidney disease, and cardiovascular disease. As a consequence, effective therapeutics for obesity require the consideration of the peripheral abnormalities associated with obesity.

Dr. Deanne H. Hryciw
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

obesity
therapeutics
nutrition
exercise
peripheral modulators
life span
sex-differences

Published Papers (6 papers)

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Research

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16 pages, 2910 KiB

Open AccessArticle

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men

by Jan Bilski, Agnieszka Irena Mazur-Bialy, Marcin Surmiak, Magdalena Hubalewska-Mazgaj, Janusz Pokorski, Jacek Nitecki, Ewa Nitecka, Joanna Pokorska, Aneta Targosz, Agata Ptak-Belowska, Jerzy A. Zoladz and Tomasz Brzozowski

Int. J. Mol. Sci. 2020, 21(22), 8848; https://doi.org/10.3390/ijms21228848 - 23 Nov 2020

Cited by 12 | Viewed by 3182

Abstract

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined. Full article

(This article belongs to the Special Issue Peripheral Targets in Obesity: Pathologies and Therapeutics)

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20 pages, 4328 KiB

Open AccessArticle

Impact of A Cargo-Less Liposomal Formulation on Dietary Obesity-Related Metabolic Disorders in Mice

by Varsha Komalla, Behjat Sheikholeslami, Gerard Li, Bishwajit Bokshi, Yik Lung Chan, Alison Ung, Brian Gregory Oliver, Hui Chen and Mehra Haghi

Int. J. Mol. Sci. 2020, 21(20), 7640; https://doi.org/10.3390/ijms21207640 - 15 Oct 2020

Cited by 6 | Viewed by 2136

Abstract

Current therapeutic options for obesity often require pharmacological intervention with dietary restrictions. Obesity is associated with underlying inflammation due to increased tissue macrophage infiltration, and recent evidence shows that inflammation can drive obesity, creating a feed forward mechanism. Therefore, targeting obesity-induced macrophage infiltration may be an effective way of treating obesity. Here, we developed cargo-less liposomes (UTS-001) using 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC (synthetic phosphatidylcholine) as a single-agent to manage weight gain and related glucose disorders due to high fat diet (HFD) consumption in mice. UTS-001 displayed potent immunomodulatory properties, including reducing resident macrophage number in both fat and liver, downregulating liver markers involved in gluconeogenesis, and increasing marker involved in thermogenesis. As a result, UTS-001 significantly enhanced systemic glucose tolerance in vivo and insulin-stimulated cellular glucose uptake in vitro, as well as reducing fat accumulation upon ad libitum HFD consumption in mice. UTS-001 targets tissue residence macrophages to suppress tissue inflammation during HFD-induced obesity, resulting in improved weight control and glucose metabolism. Thus, UTS-001 represents a promising therapeutic strategy for body weight management and glycaemic control. Full article

(This article belongs to the Special Issue Peripheral Targets in Obesity: Pathologies and Therapeutics)

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Graphical abstract

15 pages, 2586 KiB

Open AccessArticle

Parental SIRT1 Overexpression Attenuate Metabolic Disorders Due to Maternal High-Fat Feeding

by Long T. Nguyen, Sonia Saad, Hui Chen and Carol A. Pollock

Int. J. Mol. Sci. 2020, 21(19), 7342; https://doi.org/10.3390/ijms21197342 - 05 Oct 2020

Cited by 5 | Viewed by 2339

Abstract

Maternal obesity can contribute to the development of obesity and related metabolic disorders in progeny. Sirtuin (SIRT)1, an essential regulator of metabolism and stress responses, has recently emerged as an important modifying factor of developmental programming. In this study, to elucidate the effects of parental SIRT1 overexpression on offspring mechanism, four experimental groups were included: (1) Chow-fed wild-type (WT)-dam × Chow-fed WT-sire; (2) High-fat diet (HFD)-fed WT-dam × Chow-fed WT-sire; (3) HFD-fed hemizygous SIRT1-transgenic (Tg)-dam × Chow-fed WT-sire; and (4) HFD-fed WT dam × Chow-fed Tg-sire. Our results indicate that Tg breeders had lower body weight and fat mass compared to WT counterparts and gave birth to WT offspring with reductions in body weight, adiposity and hyperlipidaemia compared to those born of WT parents. Maternal SIRT1 overexpression also reversed glucose intolerance, and normalised abnormal fat morphology and the expression of dysregulated lipid metabolism markers, including SIRT1. Despite having persistent hepatic steatosis, offspring born to Tg parents showed an improved balance of hepatic glucose/lipid metabolic markers, as well as reduced levels of inflammatory markers and TGF-β/Smad3 fibrotic signalling. Collectively, the data suggest that parental SIRT1 overexpression can ameliorate adverse metabolic programming effects by maternal obesity. Full article

(This article belongs to the Special Issue Peripheral Targets in Obesity: Pathologies and Therapeutics)

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18 pages, 3375 KiB

Open AccessArticle

The Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity

by Anna C. Simcocks, Lannie O’Keefe, Kayte A. Jenkin, Lauren M. Cornall, Esther Grinfeld, Michael L. Mathai, Deanne H. Hryciw and Andrew J. McAinch

Int. J. Mol. Sci. 2020, 21(16), 5922; https://doi.org/10.3390/ijms21165922 - 18 Aug 2020

Cited by 11 | Viewed by 2642

Abstract

O-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks. C₂C₁₂ myotubes were treated with O-1602 or O-1918 and human primary myotubes were treated with O-1918. GPR18 mRNA was expressed in the skeletal muscle of DIO rats and was up-regulated in red gastrocnemius when compared with white gastrocnemius. O-1602 had no effect on mRNA expression on selected markers for oxidative capacity, fatty acid metabolism or adiponectin signalling in gastrocnemius from DIO rats or in C₂C₁₂ myotubes, while APPL2 mRNA was up-regulated in white gastrocnemius in DIO rats treated with O-1918. In C₂C₁₂ myotubes treated with O-1918, PGC1α, NFATc1 and PDK4 mRNA were up-regulated. There were no effects of O-1918 on mRNA expression in human primary myotubes derived from obese and obese T2DM individuals. In conclusion, O-1602 does not alter mRNA expression of key pathways important for skeletal muscle energy homeostasis in obesity. In contrast, O-1918 appears to alter markers of oxidative capacity and fatty acid metabolism in C₂C₁₂ myotubes only. GPR18 is expressed in DIO rat skeletal muscle and future work could focus on selectively modulating GPR18 in a tissue-specific manner, which may be beneficial for obesity-targeted therapies. Full article

(This article belongs to the Special Issue Peripheral Targets in Obesity: Pathologies and Therapeutics)

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Review

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33 pages, 2474 KiB

Open AccessReview

From Obesity to Hippocampal Neurodegeneration: Pathogenesis and Non-Pharmacological Interventions

by Thomas Ho-yin Lee and Suk-yu Yau

Int. J. Mol. Sci. 2021, 22(1), 201; https://doi.org/10.3390/ijms22010201 - 28 Dec 2020

Cited by 33 | Viewed by 6249

Abstract

High-caloric diet and physical inactivity predispose individuals to obesity and diabetes, which are risk factors of hippocampal neurodegeneration and cognitive deficits. Along with the adipose-hippocampus crosstalk, chronically inflamed adipose tissue secretes inflammatory cytokine could trigger neuroinflammatory responses in the hippocampus, and in turn, impairs hippocampal neuroplasticity under obese and diabetic conditions. Hence, caloric restriction and physical exercise are critical non-pharmacological interventions to halt the pathogenesis from obesity to hippocampal neurodegeneration. In response to physical exercise, peripheral organs, including the adipose tissue, skeletal muscles, and liver, can secret numerous exerkines, which bring beneficial effects to metabolic and brain health. In this review, we summarized how chronic inflammation in adipose tissue could trigger neuroinflammation and hippocampal impairment, which potentially contribute to cognitive deficits in obese and diabetic conditions. We also discussed the potential mechanisms underlying the neurotrophic and neuroprotective effects of caloric restriction and physical exercise by counteracting neuroinflammation, plasticity deficits, and cognitive impairments. This review provides timely insights into how chronic metabolic disorders, like obesity, could impair brain health and cognitive functions in later life. Full article

(This article belongs to the Special Issue Peripheral Targets in Obesity: Pathologies and Therapeutics)

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13 pages, 1036 KiB

Open AccessReview

Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis

by Olivia Patsalos, Bethan Dalton and Hubertus Himmerich

Int. J. Mol. Sci. 2020, 21(17), 6290; https://doi.org/10.3390/ijms21176290 - 31 Aug 2020

Cited by 32 | Viewed by 3472

Abstract

Inhibitors of the IL-6 signaling pathway, such as tocilizumab, are frequently administered for the treatment of immune diseases, e.g., rheumatoid arthritis and multicentric Castleman’s disease. The aim of this systematic review and meta-analysis was to ascertain the effects of IL-6 pathway inhibitors on weight and body mass index (BMI). Using PRISMA guidelines, we systematically reviewed relevant articles from three databases (PubMed, OVID, EMBASE). A random effects model was used to estimate standardized mean change (SMCC). Ten studies with a total of 1531 patients were included in the meta-analysis for weight and ten studies with a total of 1537 patients were included in the BMI meta-analysis. The most commonly administered IL-6 pathway inhibitor was tocilizumab. IL-6 pathway inhibitors were associated with increases in weight (SMCC = 0.09, p = 0.016, 95% CI [0.03, 0.14]) and BMI (SMCC = 0.10, p = 0.0001, 95% CI [0.05, 0.15]). These findings suggest that the IL-6 pathway is involved in weight regulation. Modulating IL-6 signaling may be a potential future therapeutic avenue used as an adjunct for the treatment of disorders associated with weight changes, such as cancer cachexia and anorexia nervosa. Full article

(This article belongs to the Special Issue Peripheral Targets in Obesity: Pathologies and Therapeutics)

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