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Biomedicines
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Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes
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Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes

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

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 22659

Special Issue Editors

Dr. Chia-Chien Hsieh

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Guest Editor
Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan
Interests: food bioactives; nutritional immunology; nutrition and cancer; nutritional and metabolic diseases; obesity-related metabolic and immune disorders
Dr. Blanca Hernández-Ledesma

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Guest Editor
Instituto de Investigación en Ciencias de la Alimentación (CIAL), Consejo Superior de Investigaciones Científicas (CSIC). c/ Nicolás Cabrera 9, 28049 Madrid, Spain
Interests: bioactive peptides; food proteins; multifuncionality; digestion; bioavailability; inflammation-associated diseases; chemopreventive activity; peptidomics; antioxidant activity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity is considered a critical issue and a global health problem worldwide. Accumulating evidence shows that obesity increases the risk of noncommunicable diseases, such as cardiovascular disease, osteoarthritis, cancer, metabolic dysfunction, and type 2 diabetes mellitus (T2DM). During adiposity, adipocytes behave as an endocrine organ releasing mediators such as adipokines, cytokines, and chemokines to recruit multiple kinds of immune cells infiltrated into the adipose tissues, resulting in the development of these chronic disorders. Pancreas of diabetic patients is unable to produce enough insulin to maintain normal blood glucose levels or show resistance to the effect of insulin, thereby resulting in hyperglycemia. Moreover, these patients develop severe symptoms and higher mortality rates during pathogenic infection.

Epidemiological and experimental studies have evidenced that people with overweight or obesity tend to develop T2DM, named diabesity. The potential mechanisms implied in the pathogenesis of T2DM include abnormal lipid profile and metabolites, immune dysregulation, oxidative stress, alterations in the insulin and glucose uptake signaling, mitochondrial dysfunction, and metabolic disorder. One of the best strategies to prevent diabetes is lifestyle modification, including physical activity and a healthy diet, and maintaining appropriate body weight. Moreover, the inclusion in the daily intake of antidiabetic compounds derived from natural sources and foods, has been recognized as a promising alternative because of their safety and lack of adverse side effects. Thus, the search for new sources of antidiabetic compounds and the demonstration of their beneficial effects is an area of great interest for the prevention/management of this global epidemic issue.

This Special Issue will include original research and in-depth reviews with the most recent insights into topics related to the (1) molecular and biochemical mechanisms of obesity and diabetes; (2) metabolic syndrome; (3) immunomodulation for obesity and diabetes; (4) and new natural preventive/therapeutic strategies for treating obesity and diabetes, and their associated disorders.

Dr. Chia-Chien Hsieh
Dr. Blanca Hernández-Ledesma
Guest Editors

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. 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

  • diabetes
  • obesity
  • metabolic syndrome
  • insulin resistance
  • inflammatory cytokines
  • adipokines
  • immunomodulation
  • glucose utilization
  • lipid metabolism
  • natural or food compounds

Published Papers (8 papers)

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Research

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16 pages, 3995 KiB  
Article
Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism
by Lei Wu, Zi-Han Lin, Xin-Jian Lu, Xuan Hu, Hao-Jie Zhong, De-Jiang Lin, Tao Liu, Jia-Ting Xu, Wen-Ying Lin, Qing-Ping Wu and Xing-Xiang He
Biomedicines 2023, 11(9), 2415; https://doi.org/10.3390/biomedicines11092415 - 29 Aug 2023
Viewed by 1001
Abstract
Background: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients. Methods: The [...] Read more.
Background: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients. Methods: The changes in body mass index (BMI = weight (kg)/height (m)2), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics. Results: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism. Conclusion: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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10 pages, 587 KiB  
Article
The Level of Intima-Media Thickness in Patients with Metabolic Syndrome in Poland Depending on the Prevalence of Type 2 Diabetes
by Marcin Gierach and Roman Junik
Biomedicines 2023, 11(6), 1510; https://doi.org/10.3390/biomedicines11061510 - 23 May 2023
Viewed by 857
Abstract
Background: Metabolic syndrome (MetS), increasingly diagnosed among the Polish population, is a combination of factors that are associated with an increased risk of atherosclerosis and cardiovascular diseases. Intima-media thickness (IMT) of the common carotid artery has been suggested as, simply, a non-invasive and [...] Read more.
Background: Metabolic syndrome (MetS), increasingly diagnosed among the Polish population, is a combination of factors that are associated with an increased risk of atherosclerosis and cardiovascular diseases. Intima-media thickness (IMT) of the common carotid artery has been suggested as, simply, a non-invasive and reproducible marker of the early stages of the atherosclerotic process. The carotid IMT can also be a strong predictor of future cerebral and cardiovascular events. The aim of our study was to evaluate atherosclerotic lesions in carotid vessels in patients with MetS depending on the presence of DMt2 and to assess which demographic factors affect the level of IMT. The study involved 335 subjects diagnosed with MetS, including 211 females (65%) and 124 males (37%) aged 37–82. The diagnosis of MetS was made on the basis of the International Diabetes Federation (IDF) criteria. The patients were divided into two subgroups: with DMt2 and without DMt2. The value of IMT depended on gender, education, and smoking status. We noticed that patients with DMt2 had the highest measurement of IMT compared with other groups (1.01 vs. 0.98). Additionally, a statistically significant difference between the subgroup with DMt2 and those without DMt2 was found (1.01 vs. 0.92; p < 0.005). Ultrasound assessment of the carotid IMT should be used more often in the diagnosis and monitoring of high cardiovascular risk and early progression of atherosclerosis, especially in patients with MetS with current DMt2. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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11 pages, 473 KiB  
Article
Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes
by Angelo Maria Patti, Rosaria Vincenza Giglio, Alberto Allotta, Andreina Bruno, Tommaso Di Bella, Anca Pantea Stoian, Marcello Ciaccio and Manfredi Rizzo
Biomedicines 2023, 11(5), 1362; https://doi.org/10.3390/biomedicines11051362 - 04 May 2023
Cited by 3 | Viewed by 2371
Abstract
Background: Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist. Several trials reported the protective effect of injectable semaglutide on cardiovascular (CV) risk by reducing major adverse cardiovascular events in type 2 diabetes patients. Strong preclinical evidence supports the CV benefits of semaglutide [...] Read more.
Background: Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist. Several trials reported the protective effect of injectable semaglutide on cardiovascular (CV) risk by reducing major adverse cardiovascular events in type 2 diabetes patients. Strong preclinical evidence supports the CV benefits of semaglutide through an effect on atherosclerosis. However, scant evidence is available about the protective mechanisms of semaglutide in clinical practice. Methods: A retrospective observational study was conducted among consecutive type 2 diabetes patients treated with injectable semaglutide in Italy between November 2019 and January 2021 when the drug was first available in the country. The primary aims were the assessment of the carotid intima-media thickness (cIMT) and hemoglobin A1c (HbA1c) levels. The secondary aims were the evaluation of anthropometric, glycemic, and hepatic parameters and plasma lipids, including the assessment of the triglyceride/high-density lipoprotein ratio as an indirect marker of atherogenic small, dense low-density lipoprotein particles. Results: Injectable semaglutide reduced HbA1c and cIMT. An improvement in CV risk factors and the triglyceride/high-density lipoprotein ratio was reported. Moreover, through correlation analyses, we found that hepatic fibrosis and steatosis indices and the anthropometric, hepatic, and glycemic parameters, as well as plasma lipids, were unrelated to the variations in cIMT and HbA1c. Conclusions: Our findings suggest the effect of injectable semaglutide on atherosclerosis as a key CV protective mechanism. Considering the favorable effects on atherogenic lipoproteins and hepatic steatosis indices, our results support the pleiotropic effect of semaglutide beyond glycemic control. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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16 pages, 20462 KiB  
Article
Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats
by Sutharinee Likitnukul, Sumpun Thammacharoen, Orada Sriwatananukulkit, Chanathip Duangtha, Ruedee Hemstapat, Chotchanit Sunrat, Supachoke Mangmool and Darawan Pinthong
Biomedicines 2023, 11(4), 1050; https://doi.org/10.3390/biomedicines11041050 - 29 Mar 2023
Cited by 3 | Viewed by 2249
Abstract
Obesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity. [...] Read more.
Obesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity. Nonetheless, it is possible that short-term GH administration had no impact on insulin sensitivity. In this study, the effect of short-term GH administration on liver lipid metabolism and the effector molecules of GH and insulin receptors were investigated in diet-induced obesity (DIO) rats. Recombinant human GH (1 mg/kg) was then administered for 3 days. Livers were collected to determine the hepatic mRNA expression and protein levels involved in lipid metabolism. The expression of GH and insulin receptor effector proteins was investigated. In DIO rats, short-term GH administration significantly reduced hepatic fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) mRNA expression while increasing carnitine palmitoyltransferase 1A (CPT1A) mRNA expression. Short-term GH administration reduced hepatic FAS protein levels and downregulated gene transcription of hepatic fatty acid uptake and lipogenesis, while increasing fatty acid oxidation in DIO rats. DIO rats had lower hepatic JAK2 protein levels but higher IRS-1 levels than control rats due to hyperinsulinemia. Our findings suggest that short-term GH supplementation improves liver lipid metabolism and may slow the progression of NAFLD, where GH acts as the transcriptional regulator of related genes. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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20 pages, 20077 KiB  
Article
Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance
by M. Carmen Navarro-Ruiz, M. Carmen Soler-Vázquez, Alberto Díaz-Ruiz, Juan R. Peinado, Andrea Nieto Calonge, Julia Sánchez-Ceinos, Carmen Tercero-Alcázar, Jaime López-Alcalá, Oriol A. Rangel-Zuñiga, Antonio Membrives, José López-Miranda, María M. Malagón and Rocío Guzmán-Ruiz
Biomedicines 2022, 10(12), 3032; https://doi.org/10.3390/biomedicines10123032 - 24 Nov 2022
Cited by 1 | Viewed by 1479
Abstract
Background: Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress [...] Read more.
Background: Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress and metabolic dysfunction. The identification of specific carbonylated proteins in adipose tissue could provide novel biomarkers of oxidative damage related to metabolic status (i.e prediabetes). Thus, we aimed at characterizing the subcutaneous and omental human adipose tissue carbonylome in obesity-associated insulin resistance. Methods: 2D-PAGE was used to identify carbonylated proteins, and clinical correlations studies and molecular biology approaches including intracellular trafficking, reactive oxygen species assay, and iron content were performed using in vitro models of insulin resistance. Results: The carbonylome of human adipose tissue included common (serotransferrin, vimentin, actin, and annexin A2) and depot-specific (carbonic anhydrase and α-crystallin B in the subcutaneous depot; and α-1-antitrypsin and tubulin in the omental depot) differences that point out the complexity of oxidative stress at the metabolic level, highlighting changes in carbonylated transferrin expression. Posterior studies using in vitro prediabetic model evidence alteration in transferrin receptor translocation, linked to the prediabetic environment. Finally, ligand-receptor molecular docking studies showed a reduced affinity for carbonylated transferrin binding to its receptor compared to wild-type transferrin, emphasizing the role of transferrin carbonylation in the link between oxidative stress and metabolic dysfunction. Conclusions: The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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14 pages, 3627 KiB  
Article
Potential Effects of Resistant Exercise on Cognitive and Muscle Functions Mediated by Myokines in Sarcopenic Obese Mice
by Gahyun Lim, Heaji Lee and Yunsook Lim
Biomedicines 2022, 10(10), 2529; https://doi.org/10.3390/biomedicines10102529 - 10 Oct 2022
Cited by 7 | Viewed by 1783
Abstract
Recently, it has been demonstrated that in sarcopenic obesity (SO), physical activity could improve cognitive functions. Moreover, previous studies suggested that muscle contraction could influence cognitive function via myokines. This study investigated the potential effects of resistant exercise on cognitive and muscle functions [...] Read more.
Recently, it has been demonstrated that in sarcopenic obesity (SO), physical activity could improve cognitive functions. Moreover, previous studies suggested that muscle contraction could influence cognitive function via myokines. This study investigated the potential effects of resistant exercise on cognitive and muscle functions in SO. SO was induced by a high-fat diet treatment for 8 weeks in 8-month-old male C57BL/6J mice. Then, resistant exercise (ladder climbing) for 8 weeks was performed. Muscle and cognitive function tests and morphological analysis were conducted. The protein levels of myokines were investigated in muscle, plasma, and the hippocampus in sarcopenic obese mice. Muscle and cognitive functions were significantly elevated in the obesity-exercise group (EX) compared to the obesity-control group (OB). Interestingly, muscle function was positively correlated with cognitive function. Abnormal morphological changes in the hippocampus were ameliorated in EX compared to OB, but not in the muscle. Protein levels of cognitive function-related myokines and energy metabolism-related markers in EX were significantly elevated in both muscle and hippocampus compared to those in OB. Interestingly, the protein level of brain-derived neurotrophic factor (BDNF) in EX was simultaneously increased in all tissues including muscle, plasma, and hippocampus compared to that in OB. In conclusion, modulation of muscle-derived cognitive function-related myokines in various pathological conditions via a resistant exercise could be a possible way of relieving muscle and cognitive dysfunction. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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Review

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23 pages, 1314 KiB  
Review
Timing Is Important—Management of Metabolic Syndrome According to the Circadian Rhythm
by Ksenija Zečević, Nataša Popović, Aleksandra Vuksanović Božarić, Mihailo Vukmirović, Manfredi Rizzo and Emir Muzurović
Biomedicines 2023, 11(4), 1171; https://doi.org/10.3390/biomedicines11041171 - 13 Apr 2023
Cited by 2 | Viewed by 3726
Abstract
Physiological processes occur in accordance with a rhythm regulated by the endogenous biological clock. This clock is programmed at the molecular level and synchronized with the daily light–dark cycle, as well as activities such as feeding, exercise, and social interactions. It consists of [...] Read more.
Physiological processes occur in accordance with a rhythm regulated by the endogenous biological clock. This clock is programmed at the molecular level and synchronized with the daily light–dark cycle, as well as activities such as feeding, exercise, and social interactions. It consists of the core clock genes, Circadian Locomotor Output Cycles Protein Kaput (CLOCK) and Brain and Muscle Arnt-Like protein 1 (BMAL1), and their products, the period (PER) and cryptochrome (CRY) proteins, as well as an interlocked feedback loop which includes reverse-strand avian erythroblastic leukemia (ERBA) oncogene receptors (REV-ERBs) and retinoic acid-related orphan receptors (RORs). These genes are involved in the regulation of metabolic pathways and hormone release. Therefore, circadian rhythm disruption leads to development of metabolic syndrome (MetS). MetS refers to a cluster of risk factors (RFs), which are not only associated with the development of cardiovascular (CV) disease (CVD), but also with increased all-cause mortality. In this review, we consider the importance of the circadian rhythm in the regulation of metabolic processes, the significance of circadian misalignment in the pathogenesis of MetS, and the management of MetS in relation to the cellular molecular clock. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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23 pages, 674 KiB  
Review
Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction
by Alina Kuryłowicz
Biomedicines 2023, 11(3), 690; https://doi.org/10.3390/biomedicines11030690 - 24 Feb 2023
Cited by 13 | Viewed by 8220
Abstract
Menopause-related decline in estrogen levels is accompanied by a change in adipose tissue distribution from a gynoid to an android and an increased prevalence of obesity in women. These unfavorable phenomena can be partially restored by hormone replacement therapy, suggesting a significant role [...] Read more.
Menopause-related decline in estrogen levels is accompanied by a change in adipose tissue distribution from a gynoid to an android and an increased prevalence of obesity in women. These unfavorable phenomena can be partially restored by hormone replacement therapy, suggesting a significant role for estrogen in the regulation of adipocytes’ function. Indeed, preclinical studies proved the involvement of these hormones in adipose tissue development, metabolism, and inflammatory activity. However, the relationship between estrogen and obesity is bidirectional. On the one hand-their deficiency leads to excessive fat accumulation and impairs adipocyte function, on the other-adipose tissue of obese individuals is characterized by altered expression of estrogen receptors and key enzymes involved in their synthesis. This narrative review aims to summarize the role of estrogen in adipose tissue development, physiology, and in obesity-related dysfunction. Firstly, the estrogen classification, synthesis, and modes of action are presented. Next, their role in regulating adipogenesis and adipose tissue activity in health and the course of obesity is described. Finally, the potential therapeutic applications of estrogen and its derivates in obesity treatment are discussed. Full article
(This article belongs to the Special Issue Molecular Regulators and Therapeutic Strategies for Obesity and Diabetes)
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