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From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for...
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From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 14020

Special Issue Editors

Dr. Abhishek Gupta

E-Mail Website
Guest Editor
Department of Biochemistry and Structural Biology, Joe R. & Teresa Lozano Long School of Medicine, University of Texas Health Science center, San Antonio, TX, USA
Interests: metabolic disease; lipid metabolism; type 2 diabetes; obesity
Special Issues, Collections and Topics in MDPI journals
Dr. Sandeep Kumar

E-Mail Website
Guest Editor
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
Interests: diabetes; obesity; PPARg; necroptosis; sarcopenia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity has reached alarming proportions, affecting over half a billion adults worldwide. It serves as a major risk factor for type 2 diabetes, hypertension, cardiovascular diseases, cancers, and infection. The link between type 2 diabetes and obesity is well established, accompanied with insulin resistance and hyperinsulinemia, intensifying the severity of the disease. These metabolic disorders contribute to an overburdened healthcare system, increased mortality, and overall diminished quality of life. Drugs, used alone or in combination with lifestyle modifications and surgery, are a cornerstone for treatment. However, the efficacy of many drugs designed to manage metabolic disorders is suboptimal, and they are often accompanied by off-target side effects.

This Special Issue is dedicated to exploring innovative approaches to address metabolic disorders, with a primary focus on obesity, type 2 diabetes, and insulin resistance. The emphasis lies on the identification of novel molecules and advanced strategies to enhance drug efficacy, improve specificity, and maximize overall effectiveness in the treatment of these metabolic disorders.

Dr. Abhishek Gupta
Dr. Sandeep Kumar
Guest Editors

Manuscript Submission Information

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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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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
  • insulin resistance
  • lipid metabolism
  • drug discovery

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Published Papers (5 papers)

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Research

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10 pages, 1082 KiB  
Article
Obesity, but Not Overweight, Is Associated with Increased Presepsin Levels in Infection-Free Individuals: An Exploratory Study
by Theocharis Koufakis, Dimitrios Kouroupis, Georgios Dimakopoulos, Theofylaktos Georgiadis, Areti Kourti, Panagiotis Doukelis, Ioanna Zografou, Dimitrios Patoulias, Djordje S. Popovic, Athina Pyrpasopoulou, Luca Busetto, Alexander Kokkinos, Vasilios Tsimihodimos, Kalliopi Kotsa, Michael Doumas and Kali Makedou
Biomedicines 2025, 13(3), 701; https://doi.org/10.3390/biomedicines13030701 - 12 Mar 2025
Cited by 1 | Viewed by 744
Abstract
Background/Objectives: Intestinal dysbiosis and systemic inflammation are involved in the pathophysiology of obesity and its complications. Presepsin is a recently discovered inflammation marker, being the soluble form of the bacterial lipopolysaccharide (LPS) receptor. Due to the imbalance of the gut flora and [...] Read more.
Background/Objectives: Intestinal dysbiosis and systemic inflammation are involved in the pathophysiology of obesity and its complications. Presepsin is a recently discovered inflammation marker, being the soluble form of the bacterial lipopolysaccharide (LPS) receptor. Due to the imbalance of the gut flora and subsequent disruption of the intestinal barrier, circulating LPS levels have been found to be elevated in patients with metabolic diseases, even in the absence of infection. However, to date, no studies have evaluated whether obesity is associated with elevated presepsin levels. Methods: The present study included 81 participants (61.7% women, 27 with obesity, 34 with overweight, and 20 controls with normal body mass index), all free of infection and diabetes mellitus. Presepsin was measured in serum by ELISA, and its concentrations were compared between the groups. Results: The obesity group had higher presepsin levels compared to controls (8.09 vs. 4.45 ng/mL, p = 0.06). When participants with a history of cardiovascular disease were excluded from the analysis and adjusting for multiple confounders through a regression model, the obesity group had higher presepsin values than the overweight and control groups (5.84 vs. 3.32 ng/mL, p = 0.016). In contrast, the overweight group had lower concentrations than both the obesity group (p = 0.005) and the controls (p = 0.031). We did not find an association between presepsin and 25-hydroxy vitamin D levels (p = 0.368). Conclusions: Although the cross-sectional character of the study cannot demonstrate causal relationships, the results could potentially suggest that systemic inflammation is implicated in the pathogenesis of obesity through the disruption of the intestinal barrier. However, the findings should only be seen as hypothesis-generating. The reduction in presepsin in the overweight state is an interesting finding that deserves further investigation. Full article
(This article belongs to the Special Issue From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights)
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13 pages, 3274 KiB  
Article
Carnosic Acid (CA) Induces a Brown Fat-like Phenotype, Increases Mitochondrial Biogenesis, and Activates AMPK in 3T3-L1 Adipocytes
by Filip Vlavcheski, Rebecca E. K. MacPherson, Val Fajardo, Newman Sze and Evangelia Tsiani
Biomedicines 2024, 12(7), 1569; https://doi.org/10.3390/biomedicines12071569 - 15 Jul 2024
Cited by 2 | Viewed by 2150
Abstract
Adipose tissue plays a crucial role in regulating metabolic homeostasis, and its dysfunction in obesity leads to insulin resistance and type 2 diabetes (T2D). White adipose tissue (WAT) primarily stores energy as lipids, while brown adipose tissue (BAT) regulates thermogenesis by dissipating energy [...] Read more.
Adipose tissue plays a crucial role in regulating metabolic homeostasis, and its dysfunction in obesity leads to insulin resistance and type 2 diabetes (T2D). White adipose tissue (WAT) primarily stores energy as lipids, while brown adipose tissue (BAT) regulates thermogenesis by dissipating energy as heat. The process of browning involves the transdifferentiation of WAT into brown-like or beige adipocytes, which exhibit a similar phenotype as BAT. The browning of WAT is an attractive approach against obesity and T2D, and the activation of the energy sensor AMP-activated protein kinase (AMPK) has been shown to play a role in browning. Carnosic acid (CA), a polyphenolic diterpene, found in many plants including rosemary, is reported to possess potent antioxidant, anti-inflammatory, and anti-hyperglycemic properties. The limited evidence available indicates that CA activates AMPK and may have anti-obesity and antidiabetic potential; however, the effects in adipocyte browning remain largely unexplored. This study aimed to examine the effects of CA on the markers of adipocyte browning. The treatment of 3T3L1 adipocytes with CA activated AMPK, reduced lipid accumulation, and increased the expression of browning protein markers (UCP-1, PGC-1α, PRDM16, and TFAM) and mitochondrial biogenesis. The use of compound C, an AMPK inhibitor, significantly attenuated the effects of CA, indicating AMPK involvement. These studies demonstrate that CA can activate AMPK and stimulate the browning of white adipocytes. Future animal and human studies are required to examine the effects of CA in vivo. Full article
(This article belongs to the Special Issue From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights)
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Review

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40 pages, 3058 KiB  
Review
Therapeutic Potential of Medicinal Plants and Their Phytoconstituents in Diabetes, Cancer, Infections, Cardiovascular Diseases, Inflammation and Gastrointestinal Disorders
by Prawej Ansari, Alexa D. Reberio, Nushrat J. Ansari, Sandeep Kumar, Joyeeta T. Khan, Suraiya Chowdhury, Fatma Mohamed Abd El-Mordy, J. M. A. Hannan, Peter R. Flatt, Yasser H. A. Abdel-Wahab and Veronique Seidel
Biomedicines 2025, 13(2), 454; https://doi.org/10.3390/biomedicines13020454 - 12 Feb 2025
Cited by 3 | Viewed by 5213
Abstract
Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and [...] Read more.
Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action. Full article
(This article belongs to the Special Issue From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights)
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14 pages, 628 KiB  
Review
Impact of Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i) Therapy on Dementia and Cognitive Decline
by Antonio Lardaro, Ludovica Quarta, Stefania Pagnotta, Giorgio Sodero, Sandro Mariani, Maria Del Ben, Giovambattista Desideri, Evaristo Ettorre and Francesco Baratta
Biomedicines 2024, 12(8), 1750; https://doi.org/10.3390/biomedicines12081750 - 3 Aug 2024
Cited by 19 | Viewed by 2747
Abstract
Dementia is an age-related syndrome characterized by the progressive deterioration of cognition and capacity for independent living. Diabetes is often associated with cognitive decline and shares similar pathophysiological mechanisms with dementia, such as systemic inflammation, oxidative stress, insulin resistance, and advanced glycation end-products [...] Read more.
Dementia is an age-related syndrome characterized by the progressive deterioration of cognition and capacity for independent living. Diabetes is often associated with cognitive decline and shares similar pathophysiological mechanisms with dementia, such as systemic inflammation, oxidative stress, insulin resistance, and advanced glycation end-products formation. Therefore, adequate diabetes management may reduce the risk of cognitive decline, especially in patients with other comorbidities and risk factors. The sodium glucose cotransporter inhibitors (SGLT2i) regulate renal glucose reabsorption by blocking the SGLT2 cotransporters located in the proximal tubules, causing glycosuria and intraglomerular pressure reduction. Their use helps to lower blood pressure by modifying sodium and water homeostasis; these drugs are also commonly used in the treatment of heart failure and chronic kidney disease, while recently, a potential neuroprotective role in the central nervous system has been suggested. The aim of our scoping review is to analyze current evidence about the potential neuroprotective effects of SGLT2i in adult patients. We performed a scoping literature review to evaluate the effect of SGLT2i on dementia, mild cognitive impairment (MCI) and Alzheimer’s disease incidence and progression. The screening process was performed through different searches on PubMed and EMBASE, evaluating original works published up to January 2024. In conclusion, the use of SGLT2i could be associated with a neuroprotective effect in patients with diabetes, reducing the incidence or the progression of MCI and dementia. Further prospective studies are needed to validate this hypothesis and to evaluate the effectiveness of this class of drugs in normal glycemic profile patients. Full article
(This article belongs to the Special Issue From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights)
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Other

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13 pages, 1528 KiB  
Systematic Review
Dyslipidemia in Pregnancy: A Systematic Review of Molecular Alterations and Clinical Implications
by Agnesa Preda, Silviu-Daniel Preda, Maria Mota, Dominic Gabriel Iliescu, Lucian George Zorila, Alexandru Cristian Comanescu, Adina Mitrea, Diana Clenciu, Eugen Mota and Ionela Mihaela Vladu
Biomedicines 2024, 12(10), 2252; https://doi.org/10.3390/biomedicines12102252 - 3 Oct 2024
Cited by 2 | Viewed by 2469
Abstract
Background: Dyslipidemia in pregnancy presents unique clinical challenges due to its effects on maternal and fetal health. This systematic review hypothesizes that molecular alterations in lipid metabolism during pregnancy contribute to adverse pregnancy outcomes and seeks to identify the clinical implications of these [...] Read more.
Background: Dyslipidemia in pregnancy presents unique clinical challenges due to its effects on maternal and fetal health. This systematic review hypothesizes that molecular alterations in lipid metabolism during pregnancy contribute to adverse pregnancy outcomes and seeks to identify the clinical implications of these changes. The rationale behind this review stems from the increased risk of complications such as preeclampsia, intrauterine growth restriction, and acute pancreatitis associated with dyslipidemia in pregnancy. The primary objective is to examine the interplay between lipid metabolism and pregnancy outcomes. Methods: To achieve this, a systematic review following PRISMA guidelines was conducted, with a comprehensive search of the PubMed database covering articles from January 2014 to June 2024. Inclusion criteria focused on studies assessing molecular alterations and clinical outcomes of dyslipidemia in pregnancy, while case reports and relevant clinical trials were analyzed to evaluate both maternal and fetal outcomes. A total of 12 studies were included in the final analysis. Results: This study provided evidence of the need for early detection and management strategies to reduce risks. The outcomes revealed significant associations between dyslipidemia and adverse maternal outcomes such as preeclampsia, gestational diabetes, and pancreatitis, as well as fetal outcomes like preterm birth and fetal distress. Conclusions: Early lipid monitoring and intervention are crucial in mitigating these risks and suggests that a multidisciplinary approach is necessary to improve maternal and fetal health in pregnancies complicated by dyslipidemia. Full article
(This article belongs to the Special Issue From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights)
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