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Cellular and Clinical Mechanisms of Obesity and Its Complications

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

Deadline for manuscript submissions: closed (1 October 2022) | Viewed by 22261

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Special Issue Editor

Prof. Dr. Bessie E. Spiliotis

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Guest Editor

Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Patras School of Medicine, Panepistimioupoli, TK 26504 Patras, Greece
Interests: cellular and clinical mechanisms of childhood obesity; cellular and clinical mechanism of growth hormone and growth hormone disorders; diabetes mellitus in children
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Special Issue Information

Dear Colleagues,

Obesity is a major public health issue which is associated with a high risk of the development of metabolic disorders not only during adulthood but also during adolescence, including insulin resistance, dyslipidemia, hypertension, endothelial dysfunction, and diabetes mellitus type 2. The major role of fat distribution in the development of these complications is well-documented, and abnormal visceral adiposity has been associated with metabolic dysregulation and cardiovascular disease. The discovery of adipokines and the role they play in energy homeostasis, insulin sensitization, inflammation, vascular reactivity, cell proliferation, and tissue remodeling has played a major role in deciphering many of the molecular mechanisms involved in the complications of obesity. In addition, research investigating insulin dynamics and adiponectin pathways in the adipose tissue of abdominal and visceral fat in cases of severe obesity have opened up new horizons for understanding the key cellular factors involved in metabolic dysregulation. This has led to new medications and methods to prevent and treat many of the problems associated with severe obesity. Furthermore, recognition of the role that chronic inflammation and increased oxidative stress play in the disorders of obesity have also significantly assisted in this process.

This Special Issue aims to summarize the current knowledge on the role of cellular and clinical mechanisms of obesity and its complications.

We look forward to your contributions.

Prof. Dr. Bessie Spiliotis
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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
adipokines
insulin resistance
diabetes
metabolic disorders

Published Papers (6 papers)

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Research

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18 pages, 2228 KiB

Open AccessArticle

Metabolic Profiling of Mice with Deletion of the Orphan G Protein-Coupled Receptor, GPR37L1

by Margaret A. Mouat, Brendan P. Wilkins, Eileen Ding, Hemna Govindaraju, James L. J. Coleman, Robert M. Graham, Nigel Turner and Nicola J. Smith

Cells 2022, 11(11), 1814; https://doi.org/10.3390/cells11111814 - 1 Jun 2022

Cited by 1 | Viewed by 2431

Abstract

Understanding the neurogenic causes of obesity may reveal novel drug targets to counter the obesity crisis and associated sequelae. Here, we investigate whether the deletion of GPR37L1, an astrocyte-specific orphan G protein-coupled receptor, affects whole-body energy homeostasis in mice. We subjected male Gpr37l1^−/− mice and littermate wildtype (Gpr37l1^+/+, C57BL/6J background) controls to either 12 weeks of high-fat diet (HFD) or chow feeding, or to 1 year of chow diet, with body composition quantified by EchoMRI, glucose handling by glucose tolerance test and metabolic rate by indirect calorimetry. Following an HFD, Gpr37l1^−/− mice had similar glucose handling, body weight and fat mass compared with wildtype controls. Interestingly, we observed a significantly elevated respiratory exchange ratio in HFD- and chow-fed Gpr37l1^−/− mice during daylight hours. After 1 year of chow feeding, we again saw no differences in glucose and insulin tolerance or body weight between genotypes, nor in energy expenditure or respiratory exchange ratio. However, there was significantly lower fat mass accumulation, and higher ambulatory activity in the Gpr37l1^−/− mice during night hours. Overall, these results indicate that while GPR37L1 may play a minor role in whole-body metabolism, it is not a viable clinical target for the treatment of obesity. Full article

(This article belongs to the Special Issue Cellular and Clinical Mechanisms of Obesity and Its Complications)

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29 pages, 7944 KiB

Open AccessEditor’s ChoiceArticle

Obesity Affects the Proliferative Potential of Equine Endometrial Progenitor Cells and Modulates Their Molecular Phenotype Associated with Mitochondrial Metabolism

by Agnieszka Smieszek, Klaudia Marcinkowska, Ariadna Pielok, Mateusz Sikora, Lukas Valihrach, Elaine Carnevale and Krzysztof Marycz

Cells 2022, 11(9), 1437; https://doi.org/10.3390/cells11091437 - 24 Apr 2022

Cited by 8 | Viewed by 2753

Abstract

The study aimed to investigate the influence of obesity on cellular features of equine endometrial progenitor cells (Eca EPCs), including viability, proliferation capacity, mitochondrial metabolism, and oxidative homeostasis. Eca EPCs derived from non-obese (non-OB) and obese (OB) mares were characterized by cellular phenotype and multipotency. Obesity-induced changes in the activity of Eca EPCs include the decline of their proliferative activity, clonogenic potential, mitochondrial metabolism, and enhanced oxidative stress. Eca EPCs isolated from obese mares were characterized by an increased occurrence of early apoptosis, loss of mitochondrial dynamics, and senescence-associated phenotype. Attenuated metabolism of Eca EPCs OB was related to increased expression of pro-apoptotic markers (CASP9, BAX, P53, P21), enhanced expression of OPN, PI3K, and AKT, simultaneously with decreased signaling stabilizing cellular homeostasis (including mitofusin, SIRT1, FOXP3). Obesity alters functional features and the self-renewal potential of endometrial progenitor cells. The impaired cytophysiology of progenitor cells from obese endometrium predicts lower regenerative capacity if used as autologous transplants. Full article

(This article belongs to the Special Issue Cellular and Clinical Mechanisms of Obesity and Its Complications)

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13 pages, 3154 KiB

Open AccessArticle

Limited Metabolic Effect of the CREBRF^R457Q Obesity Variant in Mice

by Louise K. Metcalfe, Peter R. Shepherd, Greg C. Smith and Nigel Turner

Cells 2022, 11(3), 497; https://doi.org/10.3390/cells11030497 - 31 Jan 2022

Viewed by 2282

Abstract

The Arg457Gln missense variant in the CREBRF gene has previously been identified as driving excess body weight in Pacific/Oceanic populations. Intriguingly, Arg457Gln variant carriers also demonstrate paradoxical reductions in diabetes risk, indicating that the gene has a critical role in whole-body metabolism. To study the function of this variant in more detail, we generated mice on an FVB/N background with the Crebrf Arg458Gln variant knocked in to replace the endogenous Crebrf. The whole-body metabolic phenotype was characterized for male and female mice on a regular chow diet or an 8-week high-fat challenge. Regular assessment of body composition found that the Crebrf variant had no influence on total body weight or fat mass at any time point. Glucose tolerance tests demonstrated no obvious genotype effect on glucose homeostasis, with indirect calorimetry measures of whole-body energy expenditure likewise unaffected. Male chow-fed variant carriers displayed a trend towards increased lean mass and significantly reduced sensitivity to insulin administration. Overall, this novel mouse model showed only limited phenotypic effects associated with the Crebrf missense variant. The inability to recapitulate results of human association studies may invite reconsideration of the precise mechanistic link between CREBRF function and the risks of obesity and diabetes in variant allele carriers. Full article

(This article belongs to the Special Issue Cellular and Clinical Mechanisms of Obesity and Its Complications)

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19 pages, 1823 KiB

Open AccessArticle

The Response of Mitochondrial Respiration and Quantity in Skeletal Muscle and Adipose Tissue to Exercise in Humans with Prediabetes

by Lukasz Szczerbinski, Mark Alan Taylor, Urszula Puchta, Paulina Konopka, Adam Paszko, Anna Citko, Karol Szczerbinski, Joanna Goscik, Maria Gorska, Steen Larsen and Adam Kretowski

Cells 2021, 10(11), 3013; https://doi.org/10.3390/cells10113013 - 4 Nov 2021

Cited by 6 | Viewed by 3141

Abstract

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month exercise intervention. Methods: We measured clinical metabolic parameters and gathered skeletal muscle and adipose tissue biopsies before and after the three-month exercise intervention. We then assayed the number of mitochondria via citrate synthase (CS) activity and functional parameters with high-resolution respirometry. Results: In muscle, there were no differences in mitochondrial quantity or function at baseline between normoglycemics and prediabetics. However, the intervention caused improvement in CS activity, implying an increase in mitochondrial quantity. By contrast in adipose tissue, baseline differences in CS activity were present, with the lowest CS activity coincident with impaired fasting glucose and impaired glucose tolerance (IFG + IGT). Finally, CS activity, but few of the functional metrics, improved under the intervention. Conclusions: We show that in prediabetes, no differences in the function or amount of mitochondria (measured by CS activity) in skeletal muscle are apparent, but in adipose tissue of subjects with IFG + IGT, a significantly reduced activity of CS was observed. Finally, metabolic improvements under the exercise correlate to improvements in the amount, rather than function, of mitochondria in both tissues. Full article

(This article belongs to the Special Issue Cellular and Clinical Mechanisms of Obesity and Its Complications)

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Review

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20 pages, 581 KiB

Open AccessReview

The Association of Acute Phase Proteins in Stress and Inflammation-Induced T2D

by Tammy Speelman, Lieke Dale, Ann Louw and Nicolette J. D. Verhoog

Cells 2022, 11(14), 2163; https://doi.org/10.3390/cells11142163 - 11 Jul 2022

Cited by 9 | Viewed by 3392

Abstract

Acute phase proteins (APPs), such as plasminogen activator inhibitor-1 (PAI-1), serum amyloid A (SAA), and C-reactive protein (CRP), are elevated in type-2 diabetes (T2D) and are routinely used as biomarkers for this disease. These APPs are regulated by the peripheral mediators of stress (i.e., endogenous glucocorticoids (GCs)) and inflammation (i.e., pro-inflammatory cytokines), with both implicated in the development of insulin resistance, the main risk factor for the development of T2D. In this review we propose that APPs, PAI-1, SAA, and CRP, could be the causative rather than only a correlative link between the physiological elements of risk (stress and inflammation) and the development of insulin resistance. Full article

(This article belongs to the Special Issue Cellular and Clinical Mechanisms of Obesity and Its Complications)

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16 pages, 781 KiB

Open AccessReview

Obesity: The Fat Tissue Disease Version of Cancer

by Besma Boubertakh, Cristoforo Silvestri and Vincenzo Di Marzo

Cells 2022, 11(12), 1872; https://doi.org/10.3390/cells11121872 - 9 Jun 2022

Cited by 13 | Viewed by 6624

Abstract

Obesity is a disease with high potential for fatality. It perfectly fits the disease definition, as cancer does. This is because it damages body structure and functions, both mechanically and biologically, and alters physical, mental, and social health. In addition, it shares many common morbid characteristics with the most feared disease, cancer. For example, it is influenced by a sophisticated interaction between a person’s genetics, the environment, and an increasing number of other backgrounds. Furthermore, it displays abnormal cell growth and proliferation events, only limited to white fat, resulting in adipose tissue taking up an increasing amount of space within the body. This occurs through fat “metastases” and via altered signaling that further aggravates the pathology of obesity by inducing ubiquitous dishomeostasis. These metastases can be made graver by angiogenesis, which might boost diseased tissue growth. More common features with cancer include its progressive escalation through different levels of severity and its possibility of re-onset after recovery. Despite all these similarities with cancer, obesity is substantially less agitating for most people. Thus, the ideas proposed herein could have utility to sensitize the public opinion about the hard reality of obesity. This is increasingly needed, as the obesity pandemic has waged a fierce war against our bodies and society in general, while there is still doubt about whether it is a real disease or not. Hence, raising public consciousness to properly face health issues is crucial to improving our health instead of gaining weight unhealthily. It is obviously illogical to fight cancer extremely seriously on the one hand and to consider dying with obesity as self-inflicted on the other. In fact, obesity merits a top position among the most lethal diseases besides cancer. Full article

(This article belongs to the Special Issue Cellular and Clinical Mechanisms of Obesity and Its Complications)

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