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Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition

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

Deadline for manuscript submissions: 31 May 2026 | Viewed by 31571

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Prof. Dr. Marianna Lauricella

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Guest Editor

Section of Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
Interests: mechanisms of oxidative stress induction and main antioxidant systems; biochemical pathways of cell death and survival (apoptosis, necrosis, autophagy) in tumor cells; effects of phytocompounds in obesity reduction, cardiovascular risk
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Prof. Dr. Antonella D'Anneo

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Laboratory of Biochemistry, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90127 Palermo, Italy
Interests: biochemical pathways in cancer cell death (apoptosis, necrosis, necroptosis, autophagy and anoikis); nutrition and human diseases; oxidative stress; signal transduction; targeted therapies; cancer stem-like cells; analysis of the behaviours of phytocompounds in obesity treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue follows the publication of the third edition on the topic “Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity”.

https://www.mdpi.com/journal/ijms/special_issues/Prevention_Treatment_Obesity

https://www.mdpi.com/journal/ijms/special_issues/Prevention_Treatment_Obesity_2

Obesity is a serious worldwide health concern with high mortality and morbidity rates. Many drivers have been identified for its etiopathogenesis, such as an imbalance between energy intake and its expenditure, resulting from a combination of excessive food intake, a sedentary lifestyle, reduced physical activity and genetic predisposition. In addition, environmental chemicals, such as pesticides, organotins and phthalates, have also been shown to have decisive roles in promoting obesity. These obesogens represent risk factors during fetal development, predisposing offspring to weight gain later in life. Adipose tissue plays an active metabolic role in regulating energy storage and its utilization. In addition, it may be considered an endocrine organ since it produces and secretes multiple immune-modulatory proteins, known as adipokines. Through adipokines, adipose tissue regulates several important physiological functions, including insulin sensitivity and secretion, glucose and lipid metabolism, blood pressure and the function of the immune system. Adipokines can be classified as molecules with pro-inflammatory or anti-inflammatory natures. An unbalanced production of adipokines with a pro-inflammatory role in adipose tissue induces low-grade systemic inflammation in obese patients, which predisposes them to insulin resistance, type II diabetes, non-alcoholic fatty liver disease, cardiovascular disorders and cancer. Therefore, the reduction in adipose tissue in obese subjects represents an important goal for the prevention and treatment of these chronic diseases. Nowadays, there is growing interest in finding novel target compounds, both natural and synthetic, with potential action against obesity. Investigating the effects of these compounds in reducing obesity and preventing its associated diseases could provide novel insights and further advance the knowledge base in this field. We are inviting investigators to contribute either original research or review articles to this upcoming Special Issue. Papers focusing on the pathophysiology of obesity as well as on the identification of compounds capable of managing an obesity profile and disease-related conditions are welcome.

Dr. Marianna Lauricella
Dr. Antonella D'Anneo
Guest Editors

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Keywords

obesity
adipokines
obesogens
genetic predisposition
natural/synthetic compounds
cardiovascular disorders
type II diabetes
non-alcoholic fatty liver disease
cancer

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Published Papers (6 papers)

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Research

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17 pages, 5544 KB

Open AccessArticle

Comparative Anti-Obesity Potential of Cannabigerol-Dominant Cannabis sativa L. Inflorescence Extracts via Differential Regulation of Lipid Metabolism in 3T3-L1 Cells

by Ji-Ye Han, Osoung Kwon, Yun Jung Lee, Minji Choi, Bori Lee, Dae-Ki Kim, Soohyang Noh, Mansoo Cho and Young-Mi Lee

Int. J. Mol. Sci. 2026, 27(4), 1747; https://doi.org/10.3390/ijms27041747 - 11 Feb 2026

Viewed by 1552

Abstract

Obesity is a chronic metabolic disorder characterized by excessive accumulation of body fat and is a major risk factor for various diseases, including type 2 diabetes, hypertension, and cardiovascular diseases. This study investigated the anti-obesity effects of cannabigerol-dominant C. sativa inflorescence extracts (CEs) obtained using various ethanol concentrations. The extracts were analyzed by UPLC to determine their major components. Additionally, anti-obesity mechanisms of the extracts were further determined through RT-qPCR and Western blot analysis to evaluate gene and protein expression levels. A total of seven cannabinoids, including cannabigerol as a major constituent, were identified within CE. Differentiation of 3T3-L1 cells was dose-dependently inhibited by CE at all ethanol concentrations. Furthermore, the gene and protein expression levels of key adipogenic and lipogenic markers, such as PPARγ, C/EBPα, SREBP-1c, and FAS, were significantly downregulated by CE treatment. In contrast, the expression of factors involved in lipolysis and white adipose tissue browning, such as HSL, ATGL, UCP1, and PGC-1α, was markedly increased by CE treatment. These effects were enhanced in an ethanol concentration-dependent manner. In conclusion, these results demonstrate that cannabigerol-dominant C. sativa effectively mitigates obesity by suppressing adipogenesis and lipogenesis while concurrently stimulating lipolysis and white adipose tissue browning. Full article

(This article belongs to the Special Issue Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition)

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20 pages, 4190 KB

Open AccessArticle

Arthrocolin B Impairs Adipogenesis via Delaying Cell Cycle Progression During the Mitotic Clonal Expansion Period

by Guang Cao, Xuemei Liao, Shuang Zhao, Mengwen Li, Zhengyuan Xie, Jinglan Yang, Yanze Li, Zihao Zhu, Xiaoru Jin, Rui Huang, Ziyin Guo, Xuemei Niu and Xu Ji

Int. J. Mol. Sci. 2025, 26(4), 1474; https://doi.org/10.3390/ijms26041474 - 10 Feb 2025

Viewed by 1978

Abstract

Obesity and its related diseases severely threaten people’s health, causing persistently high morbidity and mortality worldwide. The abnormal proliferation and hypertrophy of adipocytes mediate the expansion of adipose tissue, which is the main cause of obesity-related diseases. Inhibition of cell proliferation during the mitotic clonal expansion (MCE) period of adipogenesis may be a promising strategy for preventing and treating obesity. Arthrocolins are a series of fluorescent dye-like complex xanthenes from engineered Escherichia coli, with potential anti-tumor and antifungal activities. However, the role and underlying mechanisms of these compounds in adipocyte differentiation remain unclear. In this study, we discovered that arthrocolin B, a member of the arthrocolin family, significantly impeded adipogenesis by preventing the accumulation of lipid droplets and triglycerides, as well as by downregulating the expression of key factors involved in adipogenesis, such as SREBP1, C/EBPβ, C/EBPδ, C/EBPα, PPARγ, and FABP4. Moreover, we revealed that this inhibition might be a consequence of cell cycle arrest during the MCE of adipocyte differentiation, most likely by modulating the p53, AKT, and ERK pathways, upregulating the expression of p21 and p27, and repressing the expression of CDK1, CDK4, Cyclin A2, Cyclin D1, and p-Rb. Additionally, arthrocolin B could promote the expression of CPT1A during adipocyte differentiation, implying its potential role in fatty acid oxidation. Overall, our research concludes that arthrocolin B has the ability to suppress the early stages of adipocyte differentiation mainly by modulating the signaling proteins involved in cell cycle progression. This work broadens our understanding of the function and mechanisms of arthrocolins in regulation of adipogenesis and might provide a potential lead compound for treating the obesity. Full article

(This article belongs to the Special Issue Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition)

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17 pages, 3198 KB

Open AccessArticle

Untargeted Metabolomic Analyses and Antilipidemic Effects of Citrus Physiological Premature Fruit Drop

by Chao Wang, Mingfang Peng, Zhipeng Gao, Qi Han, Fuhua Fu, Gaoyang Li, Donglin Su, Lvhong Huang, Jiajing Guo and Yang Shan

Int. J. Mol. Sci. 2024, 25(3), 1876; https://doi.org/10.3390/ijms25031876 - 4 Feb 2024

Cited by 8 | Viewed by 3044

Abstract

Increasingly globally prevalent obesity and related metabolic disorders have underscored the demand for safe and natural therapeutic approaches, given the limitations of weight loss drugs and surgeries. This study compared the phytochemical composition and antioxidant activity of five different varieties of citrus physiological premature fruit drop (CPFD). Untargeted metabolomics was employed to identify variations in metabolites among different CPFDs, and their antilipidemic effects in vitro were assessed. The results showed that Citrus aurantium L. ‘Daidai’ physiological premature fruit drop (DDPD) and Citrus aurantium ‘Changshan-huyou’ physiological premature fruit drop (HYPD) exhibited higher levels of phytochemicals and stronger antioxidant activity. There were 97 differential metabolites identified in DDPD and HYPD, including phenylpropanoids, flavonoids, alkaloids, organic acids, terpenes, and lipids. Additionally, DDPD and HYPD demonstrated potential antilipidemic effects against oleic acid (OA)-induced steatosis in HepG2 hepatocytes and 3T3-L1 adipocytes. In conclusion, our findings reveal the outstanding antioxidant activity and antilipidemic effects of CPFD, indicating its potential use as a natural antioxidant and health supplement and promoting the high-value utilization of this resource. Full article

(This article belongs to the Special Issue Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition)

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21 pages, 1634 KB

Open AccessReview

Mediterranean Diet Can Reduce Fat Accumulation and Obesity Progression Through Action of Plant Bioactive Molecules

by Paola Sportiello, Miriam Piccioni, Vito Flavio Licciulli, Giuseppe Cananzi, Stefania Crispi and Domenico Catalano

Int. J. Mol. Sci. 2026, 27(9), 4134; https://doi.org/10.3390/ijms27094134 - 5 May 2026

Viewed by 462

Abstract

Obesity is a multifactorial disease associated with a chronic imbalance between energy intake and energy consumption, as well as the ingestion of high-fat foods. It is widely reported that the Mediterranean Diet (MD), a dietary regimen rich in vegetables, fruits, fiber and complex polyunsaturated lipids, can positively act on obesity onset. These aliments contain bioactive molecules that exert beneficial effects on two traits often associated with obesity: lipid accumulation and imbalance in oxidative homeostasis. Additionally, they can act on metabolic pathways linked to obesity through the cross-kingdom activity of plant miRNAs. In this review, we provide an overview of the studies describing the anti-obesogenic effect of plant-based foods typical of the Mediterranean Diet. We describe the results of recent studies that link the effect of lipid reduction with the ingestion of bioactive molecules or plant miRNAs typical of MD foods. We also report how advances in bioinformatic analyses have elucidated the role of plant-derived miRNAs in metabolic homeostasis, revealing how the cross-kingdom interaction results in the anti-obesogenic action of the MD. These findings shed light on the molecular mechanisms through which the MD dietary pattern exerts its metabolic effects, suggesting new perspectives on MD nutrition-based strategies as novel therapeutic approaches for obesity. Full article

(This article belongs to the Special Issue Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition)

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15 pages, 1036 KB

Open AccessReview

Molecular Pharmacology of Vitamin C and Relevance to Health and Obesity—A Narrative Review

by Robert Beaumont Wilson, Yicong Liang, Devesh Kaushal and Anitra Carr

Int. J. Mol. Sci. 2024, 25(14), 7523; https://doi.org/10.3390/ijms25147523 - 9 Jul 2024

Cited by 14 | Viewed by 13645

Abstract

The role of food constituents as pharmacological agents is an important consideration in health and obesity. Vitamin C acts as a small molecule antioxidant but is also a co-factor for numerous transition metal-dependent enzymes involved in healthy weight and energy metabolism. Vitamin C cannot be manufactured by humans and is mainly obtained from the dietary intake of fresh fruit and vegetables. There is great variability between different nutritional guidelines in the recommended daily allowance of vitamin C. Vitamin C deficiency results from an inadequate intake of vitamin C-containing foods and also increased utilization by oxidative and carbonyl stress. Risk factors for vitamin C deficiency include cigarette smoking, malnutrition, obesity, type 2 diabetes mellitus, age, race, sex, social isolation, major surgery, and Western-type diets. Despite the common belief that vitamin C deficiency is rare in affluent countries, surveys of large populations and specific patient groups suggest otherwise. Patients with obesity typically consume highly processed, energy-dense foods which contain inadequate micronutrients. As obesity increases, larger amounts of oral vitamin C are required to achieve adequate plasma and tissue concentrations, as compared to persons with a healthy weight. This is important in the control of oxidative stress and the maintenance of homeostasis and organ function. In this narrative review, the dosage, absorption, distribution, excretion, and catabolism of vitamin C are reviewed, together with the latest findings on vitamin C pharmacology in patients with obesity. Full article

(This article belongs to the Special Issue Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition)

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32 pages, 530 KB

Open AccessReview

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment

by Gladys Maribel Hidalgo-Lozada, Angelica Villarruel-López, Karla Nuño, Abel García-García, Yaír Adonaí Sánchez-Nuño and César Octavio Ramos-García

Int. J. Mol. Sci. 2024, 25(5), 2671; https://doi.org/10.3390/ijms25052671 - 25 Feb 2024

Cited by 13 | Viewed by 9625

Abstract

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation–satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds. Full article

(This article belongs to the Special Issue Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 3rd Edition)

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