Molecular Research in Obesity

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 11534

Special Issue Editors


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Guest Editor
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Interests: obesity; bariatric surgery; leukocytes; oxidative stress; metabolic pathways
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Guest Editor
Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
Interests: obesity; metabolic disorders; inflammation; oxidative stress; mitochondrial dysfunction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity is a complex chronic disease of epidemic proportions, contributing to the increasing burdens of cardiovascular disease, type 2 diabetes, hyperlipidemia, and premature death worldwide. Although the rapid increase in obesity has been driven by environmental changes, genetic factors are also critical players in determining individual predisposition to this condition.

Obesity has been linked to adverse alterations in adipose tissue, specifically white and brown adipose tissue, that predisposes subjects to metabolic dysregulation, chronic low-grade inflammation, and dysfunction in energy storage and expenditure. These adverse alterations include the activation and/or inhibition of relevant molecular pathways regulating appetite, metabolism, energy balance, adipocyte differentiation, and thermogenesis. Although mechanisms beyond obesity and its related comorbidities have been extensively investigated, some of them have yet to be fully elucidated.

This Special Issue aims to summarize the current knowledge and advances in this field, showcasing the novel molecular mechanisms underlying obesity; to prevent the individual risk of developing obesity; and to identify novel approaches in the management of this condition.

Original research articles and reviews include (but are not limited to): elucidating the molecular underpinnings of obesity, identifying genetic factors, unraveling metabolic pathways, and exploring the functions of adipose tissue.

Dr. Zaida Abad-Jiménez
Dr. Teresa Vezza
Guest Editors

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Keywords

  • obesity
  • genetics
  • molecular pathways
  • adipose tissue
  • metabolism
  • leukocytes
  • prevention
  • new targets for treatment
  • translational studies

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Related Special Issue

Published Papers (8 papers)

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Research

Jump to: Review

9 pages, 263 KiB  
Article
Serum Fatty Acids and Inflammatory Patterns in Severe Obesity: A Preliminary Investigation in Women
by Gislene B. Lima, Nayra Figueiredo, Fabiana M. Kattah, Emilly S. Oliveira, Maria A. Horst, Ana R. Dâmaso, Lila M. Oyama, Renata G. M. Whitton, Gabriel I. M. H. de Souza, Glaucia C. Lima, João F. Mota, Raquel M. S. Campos and Flávia C. Corgosinho
Biomedicines 2024, 12(10), 2248; https://doi.org/10.3390/biomedicines12102248 - 3 Oct 2024
Viewed by 657
Abstract
Background: Inflammation plays a central role in many chronic diseases that characterize modern society. Leptin/adiponectin and adiponectin/leptin ratios have been recognized as notable markers of dysfunctional adipose tissue and, consequently, an inflammatory state. Methods: Blood samples were collected from 41 adult volunteers (40.2 [...] Read more.
Background: Inflammation plays a central role in many chronic diseases that characterize modern society. Leptin/adiponectin and adiponectin/leptin ratios have been recognized as notable markers of dysfunctional adipose tissue and, consequently, an inflammatory state. Methods: Blood samples were collected from 41 adult volunteers (40.2 ± 8.3 years) diagnosed with severe obesity (BMI 46.99; 42.98–51.91 kg/m2). The adipokines were quantified using an enzyme-linked immunosorbent assay, while the serum fatty acid analysis was conducted using chromatography. Results: The results unveiled a positive correlation between the leptin/adiponectin ratio and the 20:3n6 fatty acid (r = 0.52, p = 0.001), as well as a similar positive correlation between the adiponectin/leptin ratio and the 22:6n3 fatty acid (r = 0.74, p = 0.001). In the regression analysis, the 22:6n3 fatty acid predicted the adiponectin/leptin ratio (β = 0.76, p < 0.001), whereas C20:3 n-6 was a predictor for inflammatory markers (β = 4.84, p < 0.001). Conclusions: In conclusion, the 22:6n3 fatty acid was demonstrated to be a predictive factor for the adiponectin/leptin ratio and C20:3 n-6 was a predictor for inflammatory markers. This discovery, novel within this population, can help develop new intervention strategies aimed at controlling the inflammatory status in individuals classified as having severe obesity. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
21 pages, 6282 KiB  
Article
The Obesogenic Gut Microbiota as a Crucial Factor Defining the Depletion of Predicted Enzyme Abundance for Vitamin B12 Synthesis in the Mouse Intestine
by Anastasia A. Zabolotneva, Irina M. Kolesnikova, Ilya Yu. Vasiliev, Tatiana V. Grigoryeva, Sergei A. Roumiantsev and Aleksandr V. Shestopalov
Biomedicines 2024, 12(6), 1280; https://doi.org/10.3390/biomedicines12061280 - 9 Jun 2024
Viewed by 1074
Abstract
Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet well [...] Read more.
Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet well understood. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesized that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower predicted abundance of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(−/−) (db/db) mice, which developed severe obesity. The predicted abundance of enzymes involved in cobalamin synthesis is strongly correlated with the representation of several microbes in high-fat diet-fed mice, while there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
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11 pages, 280 KiB  
Article
HOMA-IR as a Predictor of PAI-1 Levels in Women with Severe Obesity
by Fabiana Martins Kattah, Milijana Janjusevic, Nayra Figueiredo, Emilly Santos Oliveira, Glaucia Carielo Lima, Ana Raimunda Dâmaso, Lila Missae Oyama, Alessandra Lucia Fluca, Paulo Reis Eselin de Melo, Maria Aderuza Horst, Aneta Aleksova and Flávia Campos Corgosinho
Biomedicines 2024, 12(6), 1222; https://doi.org/10.3390/biomedicines12061222 - 31 May 2024
Viewed by 872
Abstract
Background: Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a [...] Read more.
Background: Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a promising biomarker. However, PAI-1 is not part of the clinical routine due to its high cost. Therefore, it is necessary to find good predictors that would allow an indirect assessment of PAI-1. Methods: This study enrolled 47 women with severe obesity (SO). The obtained anthropometric measurements included weight, height, neck (NC), waist (WC), and hip circumference (HC). Blood samples were collected to analyse glucose and lipid profiles, C-reactive protein, liver markers, adiponectin, and PAI-1 (determined by ELISA immunoassay). Homeostasis model assessment-adiponectin (HOMA-AD), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglyceride–glucose index (TyG), and atherogenic index of plasma (AIP) were calculated. The women were grouped according to PAI-1 levels. The data were analysed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. Results: Women with SO who have higher levels of PAI-1 have lower values of high-density lipoprotein cholesterol (HDL) (p = 0.037) and QUICKI (0.020) and higher values of HOMA-AD (0.046) and HOMA-IR (0.037). HOMA-IR was demonstrated to be a good predictor of PAI-1 in this sample (B = 0.2791; p = 0.017). Conclusions: HOMA-IR could be used as a predictor of PAI-1 levels, pointing out the relevance of assessing glycaemic parameters for the prevention of CVDs in women with SO. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
17 pages, 3245 KiB  
Article
Neurosecretory Protein GM–Expressing Neurons Participate in Lipid Storage and Inflammation in Newly Developed Cre Driver Male Mice
by Yuki Narimatsu, Masaki Kato, Eiko Iwakoshi-Ukena, Shogo Moriwaki, Ayano Ogasawara, Megumi Furumitsu and Kazuyoshi Ukena
Biomedicines 2023, 11(12), 3230; https://doi.org/10.3390/biomedicines11123230 - 6 Dec 2023
Viewed by 1316
Abstract
Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory [...] Read more.
Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in male NPGM-Cre mice. Chemogenetic activation of NPGM neurons in the hypothalamus acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
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15 pages, 1555 KiB  
Article
Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
by Larysa V. Yuzefovych, Viktor M. Pastukh, Madhuri S. Mulekar, Kate Ledbetter, William O. Richards and Lyudmila I. Rachek
Biomedicines 2023, 11(9), 2514; https://doi.org/10.3390/biomedicines11092514 - 12 Sep 2023
Viewed by 1162
Abstract
While improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells were isolated from healthy [...] Read more.
While improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells were isolated from healthy controls (HC) and bariatric surgery patients before surgery and 2 weeks, 3 months, and 6 months after surgery. At baseline, the plasma level of short cf-mtDNA (ND6, ~100 bp) fragments was significantly higher in obese patients compared to HC. But there was no significant variation in mean ND6 values post-surgery. A significant positive correlation was observed between preop plasma ND6 levels and HgbA1c, ND6 and HOMA-IR 2 weeks post-surgery, and mtDNA content 6 months post-surgery. Interestingly, plasma from both HC and obese groups at all time points post-surgery contains long (~8 kb) cf-mtDNA fragments, suggesting the presence of near-intact and/or whole mitochondrial genomes. No significant variation was observed in mtDNA content post-surgery compared to baseline data in both PBM and skeletal muscle samples. Overall, bariatric surgery improved insulin sensitivity and other metabolic parameters without significant changes in plasma short cf-mtDNA levels or cellular mtDNA content. Our study provides novel insights about possible molecular mechanisms underlying the metabolic effects of bariatric surgery and suggests the development of new generalized approaches to characterize cf-mtDNA. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
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13 pages, 1800 KiB  
Article
Circulating and Exosomal microRNA-33 in Childhood Obesity
by Manuela Cabiati, Letizia Guiducci, Emioli Randazzo, Valentina Casieri, Giovanni Federico and Silvia Del Ry
Biomedicines 2023, 11(8), 2295; https://doi.org/10.3390/biomedicines11082295 - 18 Aug 2023
Viewed by 1136
Abstract
Background: MicroRNA-33 may control a wide range of different metabolic functions. Methods: This study aims to assess the miR-33a circulating profile in normal-weight (N = 20) and obese (O = 30) adolescents and to correlate its expression levels to their metabolic parameters. In [...] Read more.
Background: MicroRNA-33 may control a wide range of different metabolic functions. Methods: This study aims to assess the miR-33a circulating profile in normal-weight (N = 20) and obese (O = 30) adolescents and to correlate its expression levels to their metabolic parameters. In a subset of subjects, we compared circulating miR-33a with exosomal miR-33a. Results: Metabolic parameters were altered in O, with initial hyperinsulinemia. Circulating miR-33a was significantly higher in O than in N (p = 0.0002). Significant correlations between miR-33a and auxological and metabolic indices (Insulin p = 0.01; Cholesterol p = 0.01; LDL p = 0.01; HbA1c p = 0.01) were found. Splitting our population (O + N) into two groups, according to the median value of mRNA expression miR-33a levels (0.701), irrespective of the presence or absence of obesity, we observed that those having a higher expression of miR-33a were more frequently obese (87.5% vs. 12.5%; p < 0.0001) and had significantly increased values of auxological and metabolic parameters. Exosomes extracted from plasma of N and O carried miR-33a, and its expression was lower in O (p = 0.026). No correlations with metabolic parameters were observed. Conclusion: While exosome miR-33a does not provide any advantage, circulating miR-33a can provide important indications in an initial phase of metabolic dysfunction, stratifying obese adolescents at higher cardiometabolic risk. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
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Review

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20 pages, 936 KiB  
Review
Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies
by Ying Cheng, Shiqing Liang, Shuhan Zhang and Xiaoyan Hui
Biomedicines 2024, 12(7), 1474; https://doi.org/10.3390/biomedicines12071474 - 4 Jul 2024
Viewed by 1276
Abstract
Obesity is a complex medical condition caused by a positive imbalance between calorie intake and calorie consumption. Brown adipose tissue (BAT), along with the newly discovered “brown-like” adipocytes (called beige cells), functions as a promising therapeutic tool to ameliorate obesity and metabolic disorders [...] Read more.
Obesity is a complex medical condition caused by a positive imbalance between calorie intake and calorie consumption. Brown adipose tissue (BAT), along with the newly discovered “brown-like” adipocytes (called beige cells), functions as a promising therapeutic tool to ameliorate obesity and metabolic disorders by burning out extra nutrients in the form of heat. Many studies in animal models and humans have proved the feasibility of this concept. In this review, we aim to summarize the endeavors over the last decade to achieve a higher number/activity of these heat-generating adipocytes. In particular, pharmacological compounds, especially agonists to the β3 adrenergic receptor (β3-AR), are reviewed in terms of their feasibility and efficacy in elevating BAT function and improving metabolic parameters in human subjects. Alternatively, allograft transplantation of BAT and the transplantation of functional brown or beige adipocytes from mesenchymal stromal cells or human induced pluripotent stem cells (hiPSCs) make it possible to increase the number of these beneficial adipocytes in patients. However, practical and ethical issues still need to be considered before the therapy can eventually be applied in the clinical setting. This review provides insights and guidance on brown- and beige-cell-based strategies for the management of obesity and its associated metabolic comorbidities. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
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22 pages, 1369 KiB  
Review
Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction?
by Akila Lara Oliveira, Mariana Gonçalves de Oliveira, Fabíola Zakia Mónica and Edson Antunes
Biomedicines 2024, 12(5), 939; https://doi.org/10.3390/biomedicines12050939 - 23 Apr 2024
Cited by 4 | Viewed by 2003
Abstract
Methylglyoxal (MGO) is a highly reactive α-dicarbonyl compound formed endogenously from 3-carbon glycolytic intermediates. Methylglyoxal accumulated in plasma and urine of hyperglycemic and diabetic individuals acts as a potent peptide glycation molecule, giving rise to advanced glycation end products (AGEs) like arginine-derived hydroimidazolone [...] Read more.
Methylglyoxal (MGO) is a highly reactive α-dicarbonyl compound formed endogenously from 3-carbon glycolytic intermediates. Methylglyoxal accumulated in plasma and urine of hyperglycemic and diabetic individuals acts as a potent peptide glycation molecule, giving rise to advanced glycation end products (AGEs) like arginine-derived hydroimidazolone (MG-H1) and carboxyethyl-lysine (CEL). Methylglyoxal-derived AGEs exert their effects mostly via activation of RAGE, a cell surface receptor that initiates multiple intracellular signaling pathways, favoring a pro-oxidant environment through NADPH oxidase activation and generation of high levels of reactive oxygen species (ROS). Diabetic bladder dysfunction is a bothersome urological complication in patients with poorly controlled diabetes mellitus and may comprise overactive bladder, urge incontinence, poor emptying, dribbling, incomplete emptying of the bladder, and urinary retention. Preclinical models of type 1 and type 2 diabetes have further confirmed the relationship between diabetes and voiding dysfunction. Interestingly, healthy mice supplemented with MGO for prolonged periods exhibit in vivo and in vitro bladder dysfunction, which is accompanied by increased AGE formation and RAGE expression, as well as by ROS overproduction in bladder tissues. Drugs reported to scavenge MGO and to inactivate AGEs like metformin, polyphenols, and alagebrium (ALT-711) have shown favorable outcomes on bladder dysfunction in diabetic obese leptin-deficient and MGO-exposed mice. Therefore, MGO, AGEs, and RAGE levels may be critically involved in the pathogenesis of bladder dysfunction in diabetic individuals. However, there are no clinical trials designed to test drugs that selectively inhibit the MGO–AGEs–RAGE signaling, aiming to reduce the manifestations of diabetes-associated bladder dysfunction. This review summarizes the current literature on the role of MGO–AGEs–RAGE–ROS axis in diabetes-associated bladder dysfunction. Drugs that directly inactivate MGO and ameliorate bladder dysfunction are also reviewed here. Full article
(This article belongs to the Special Issue Molecular Research in Obesity)
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