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Molecular Background of Obesity and Its Impact on Therapeutic Strategies
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Molecular Background of Obesity and Its Impact on Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 20 April 2025 | Viewed by 11355

Special Issue Editor

Dr. Lukasz Buldak

E-Mail Website
Guest Editor
Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland
Interests: internal medicine; endocrinology; clinical pharmacology; obesity; metabolic diseases; hyperlipidemia; diabetes; arterial hypertension
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity is a severe, chronic and recurrent disease. It leads to grave complications, including diabetes, arterial hypertension, hyperlipidemia and metabolic-associated liver disease (MASLD), among others. The pathogeneses of the complications associated with diabetes have been extensively studied and, as a result, a large group of drugs have been successfully developed. However, the real culprit–obesity–remains elusive as a drug target. It stems from a more complex etiology that involves, among others, the central nervous system and digestive tract. Advancements in the research field have led to some improvements and the introduction of effective drugs acting on GLP-1 receptors and MC4-R, but the need for further drugs persists.

Therefore, the focus of this Special Issue is on the mechanisms of obesity and experiments on the potential pathways involved in the pathogenesis of obesity (both in vitro and in vivo). I encourage authors to present both original papers and review articles that provide further insights into the field.

Dr. Lukasz Buldak
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.

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Keywords

  • obesity
  • GLP-1
  • MC4-R
  • metabolic disease
  • in vivo
  • in vitro

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Published Papers (5 papers)

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Research

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14 pages, 2692 KiB  
Article
Effects of Bifidobacterium-Fermented Milk on Obesity: Improved Lipid Metabolism through Suppression of Lipogenesis and Enhanced Muscle Metabolism
by Hitomi Maruta, Yusuke Fujii, Naoki Toyokawa, Shoji Nakamura and Hiromi Yamashita
Int. J. Mol. Sci. 2024, 25(18), 9934; https://doi.org/10.3390/ijms25189934 - 14 Sep 2024
Viewed by 825
Abstract
Obesity is a major global health concern. Studies suggest that the gut microflora may play a role in protecting against obesity. Probiotics, including lactic acid bacteria and Bifidobacterium, have garnered attention for their potential in obesity prevention. However, the effects of Bifidobacterium [...] Read more.
Obesity is a major global health concern. Studies suggest that the gut microflora may play a role in protecting against obesity. Probiotics, including lactic acid bacteria and Bifidobacterium, have garnered attention for their potential in obesity prevention. However, the effects of Bifidobacterium-fermented products on obesity have not been thoroughly elucidated. Bifidobacterium, which exists in the gut of animals, is known to enhance lipid metabolism. During fermentation, it produces acetic acid, which has been reported to improve glucose tolerance and insulin resistance, and exhibit anti-obesity and anti-diabetic effects. Functional foods have been very popular around the world, and fermented milk is a good candidate for enrichment with probiotics. In this study, we aim to evaluate the beneficial effects of milks fermented with Bifidobacterium strains on energy metabolism and obesity prevention. Three Bifidobacterium strains (Bif-15, Bif-30, and Bif-39), isolated from newborn human feces, were assessed for their acetic acid production and viability in milk. These strains were used to ferment milk. Otsuka–Long–Evans Tokushima Fatty (OLETF) rats administered Bif-15-fermented milk showed significantly lower weight gain compared to those in the water group. The phosphorylation of AMPK was increased and the expression of lipogenic genes was suppressed in the liver of rats given Bif-15-fermented milk. Additionally, gene expression related to respiratory metabolism was significantly increased in the soleus muscle of rats given Bif-15-fermented milk. These findings suggest that milk fermented with the Bifidobacterium strain Bif-15 can improve lipid metabolism and suppress obesity. Full article
(This article belongs to the Special Issue Molecular Background of Obesity and Its Impact on Therapeutic Strategies)
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14 pages, 2466 KiB  
Article
Semaglutide Improves Liver Steatosis and De Novo Lipogenesis Markers in Obese and Type-2-Diabetic Mice with Metabolic-Dysfunction-Associated Steatotic Liver Disease
by Manuel Soto-Catalán, Lucas Opazo-Ríos, Hernán Quiceno, Iolanda Lázaro, Juan Antonio Moreno, Carmen Gómez-Guerrero, Jesús Egido and Sebastian Mas-Fontao
Int. J. Mol. Sci. 2024, 25(5), 2961; https://doi.org/10.3390/ijms25052961 - 4 Mar 2024
Cited by 1 | Viewed by 3033
Abstract
Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are [...] Read more.
Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated. We investigated the efficacy of semaglutide in halting MASLD progression using a genetic mouse model of diabesity. Leptin-receptor-deficient mice with obesity and diabetes (BKS db/db) were either untreated or administered with semaglutide for 11 weeks. Changes in food and water intake, body weight and glycemia were monitored throughout the study. Body fat composition was assessed by dual-energy X-ray absorptiometry. Upon sacrifice, serum biochemical parameters, liver morphology, lipidomic profile and liver-lipid-related pathways were evaluated. The semaglutide-treated mice exhibited lower levels of glycemia, body weight, serum markers of liver dysfunction and total and percentage of fat mass compared to untreated db/db mice without a significant reduction in food intake. Histologically, semaglutide reduced hepatic steatosis, hepatocellular ballooning and intrahepatic triglycerides. Furthermore, the treatment ameliorated the hepatic expression of de novo lipogenesis markers and modified lipid composition by increasing the amount of polyunsaturated fatty acids. The administration of semaglutide to leptin-receptor-deficient, hyperphagic and diabetic mice resulted in the amelioration of MASLD, likely independently of daily caloric intake, suggesting a direct effect of semaglutide on the liver through modulation of the lipid profile. Full article
(This article belongs to the Special Issue Molecular Background of Obesity and Its Impact on Therapeutic Strategies)
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15 pages, 3655 KiB  
Article
Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring’s Metabolic Profile in a Swine Model
by Berta Mas-Parés, Sílvia Xargay-Torrent, Gemma Carreras-Badosa, Ariadna Gómez-Vilarrubla, Maria Niubó-Pallàs, Joan Tibau, Josep Reixach, Anna Prats-Puig, Francis de Zegher, Lourdes Ibañez, Judit Bassols and Abel López-Bermejo
Int. J. Mol. Sci. 2024, 25(2), 1128; https://doi.org/10.3390/ijms25021128 - 17 Jan 2024
Viewed by 1630
Abstract
Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring’s adipose tissue [...] Read more.
Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring’s adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring’s adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes. Full article
(This article belongs to the Special Issue Molecular Background of Obesity and Its Impact on Therapeutic Strategies)
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Review

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43 pages, 1772 KiB  
Review
Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy
by Michał Nicze, Adrianna Dec, Maciej Borówka, Damian Krzyżak, Aleksandra Bołdys, Łukasz Bułdak and Bogusław Okopień
Int. J. Mol. Sci. 2024, 25(15), 8202; https://doi.org/10.3390/ijms25158202 - 27 Jul 2024
Viewed by 2578
Abstract
Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the [...] Read more.
Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain–gut–microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become “block-buster” drugs due to their effectiveness in reducing body weight and beneficial effects on the patient’s metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials. Full article
(This article belongs to the Special Issue Molecular Background of Obesity and Its Impact on Therapeutic Strategies)
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22 pages, 2565 KiB  
Review
IGF-1 and IGF-2 as Molecules Linked to Causes and Consequences of Obesity from Fetal Life to Adulthood: A Systematic Review
by Justyna Szydlowska-Gladysz, Adrianna Edyta Gorecka, Julia Stepien, Izabela Rysz and Iwona Ben-Skowronek
Int. J. Mol. Sci. 2024, 25(7), 3966; https://doi.org/10.3390/ijms25073966 - 2 Apr 2024
Cited by 1 | Viewed by 2506
Abstract
This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children’s health—from the realms of growth and puberty to the nuanced characteristics of metabolic syndrome, diabetes, liver pathology, carcinogenic potential, and cardiovascular [...] Read more.
This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children’s health—from the realms of growth and puberty to the nuanced characteristics of metabolic syndrome, diabetes, liver pathology, carcinogenic potential, and cardiovascular disorders. A comprehensive literature review was conducted using PubMed, with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method employing specific keywords related to child health, obesity, and insulin-like growth factors. This study reveals associations between insulin-like growth factor 1 and birth weight, early growth, and adiposity. Moreover, insulin-like growth factors play a pivotal role in regulating bone development and height during childhood, with potential implications for puberty onset. This research uncovers insulin-like growth factor 1 and insulin-like growth factor 2 as potential biomarkers and therapeutic targets for metabolic dysfunction-associated liver disease and hepatocellular carcinoma, and it also highlights the association between insulin-like growth factors (IGFs) and cancer. Additionally, this research explores the impact of insulin-like growth factors on cardiovascular health, noting their role in cardiomyocyte hypertrophy. Insulin-like growth factors play vital roles in human physiology, influencing growth and development from fetal stages to adulthood. The impact of maternal obesity on children’s IGF levels is complex, influencing growth and carrying potential metabolic consequences. Imbalances in IGF levels are linked to a range of health conditions (e.g., insulin resistance, glucose intolerance, metabolic syndrome, and diabetes), prompting researchers to seek novel therapies and preventive strategies, offering challenges and opportunities in healthcare. Full article
(This article belongs to the Special Issue Molecular Background of Obesity and Its Impact on Therapeutic Strategies)
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