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Natural and Synthetic Compounds for Management, Prevention and Treatment of Obesity, 2nd Edition

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: closed (28 February 2023) | Viewed by 27304

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Guest Editor
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
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Special Issue Information

Dear Colleagues,

Obesity is a serious worldwide health concern with a high incidence of mortality and morbidity. 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 occupy a decisive role 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 a pro-inflammatory or anti-inflammatory nature. 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 has been a 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 of 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

Published Papers (13 papers)

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Editorial

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6 pages, 241 KiB  
Editorial
Multimodal Strategies to Fight Obesity: Research on Tailored Therapies Based on Natural and Synthetic Compounds for Prevention, Management and Treatment
by Antonella D’Anneo and Marianna Lauricella
Int. J. Mol. Sci. 2023, 24(12), 10105; https://doi.org/10.3390/ijms241210105 - 14 Jun 2023
Cited by 1 | Viewed by 801
Abstract
In the past 50 years, the global prevalence of obesity and overweight has tripled, reaching pandemic proportions and blatantly representing an urgent problem for public health [...] Full article

Research

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19 pages, 2683 KiB  
Article
The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis
by Lilli Arndt, Andreas Lindhorst, Julia Neugebauer, Anne Hoffmann, Constance Hobusch, Vasileia-Ismini Alexaki, Adhideb Ghosh, Matthias Blüher, Christian Wolfrum, Markus Glaß and Martin Gericke
Int. J. Mol. Sci. 2023, 24(6), 5672; https://doi.org/10.3390/ijms24065672 - 16 Mar 2023
Cited by 6 | Viewed by 2077
Abstract
White adipose tissue (WAT) fibrosis, characterized by an excess of extracellular (ECM) matrix components, is strongly associated with WAT inflammation and dysfunction due to obesity. Interleukin (IL)-13 and IL-4 were recently identified as critical mediators in the pathogenesis of fibrotic diseases. However, their [...] Read more.
White adipose tissue (WAT) fibrosis, characterized by an excess of extracellular (ECM) matrix components, is strongly associated with WAT inflammation and dysfunction due to obesity. Interleukin (IL)-13 and IL-4 were recently identified as critical mediators in the pathogenesis of fibrotic diseases. However, their role in WAT fibrosis is still ill-defined. We therefore established an ex vivo WAT organotypic culture system and demonstrated an upregulation of fibrosis-related genes and an increase of α-smooth muscle actin (αSMA) and fibronectin abundance upon dose-dependent stimulation with IL-13/IL-4. These fibrotic effects were lost in WAT lacking il4ra, which encodes for the underlying receptor controlling this process. Adipose tissue macrophages were found to play a key role in mediating IL-13/IL-4 effects in WAT fibrosis as their depletion through clodronate dramatically decreased the fibrotic phenotype. IL-4-induced WAT fibrosis was partly confirmed in mice injected intraperitoneally with IL-4. Furthermore, gene correlation analyses of human WAT samples revealed a strong positive correlation of fibrosis markers with IL-13/IL-4 receptors, whereas IL13 and IL4 correlations failed to confirm this association. In conclusion, IL-13 and IL-4 can induce WAT fibrosis ex vivo and partly in vivo, but their role in human WAT remains to be further elucidated. Full article
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19 pages, 5564 KiB  
Article
Hypertrophy and ER Stress Induced by Palmitate Are Counteracted by Mango Peel and Seed Extracts in 3T3-L1 Adipocytes
by Giovanni Pratelli, Diana Di Liberto, Daniela Carlisi, Sonia Emanuele, Michela Giuliano, Antonietta Notaro, Anna De Blasio, Giuseppe Calvaruso, Antonella D’Anneo and Marianna Lauricella
Int. J. Mol. Sci. 2023, 24(6), 5419; https://doi.org/10.3390/ijms24065419 - 12 Mar 2023
Cited by 7 | Viewed by 1990
Abstract
A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase in the adipose tissue of obese subjects. Thus, reducing hypertrophy and oxidative stress in adipose tissue can represent a strategy to counteract obesity and obesity-related diseases. [...] Read more.
A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase in the adipose tissue of obese subjects. Thus, reducing hypertrophy and oxidative stress in adipose tissue can represent a strategy to counteract obesity and obesity-related diseases. In this context, the present study showed how the peel and seed extracts of mango (Mangifera indica L.) reduced lipotoxicity induced by high doses of sodium palmitate (PA) in differentiated 3T3-L1 adipocytes. Mango peel (MPE) and mango seed (MSE) extracts significantly lowered PA-induced fat accumulation by reducing lipid droplet (LDs) and triacylglycerol (TAGs) content in adipocytes. We showed that MPE and MSE activated hormone-sensitive lipase, the key enzyme of TAG degradation. In addition, mango extracts down-regulated the adipogenic transcription factor PPARγ as well as activated AMPK with the consequent inhibition of acetyl-CoA-carboxylase (ACC). Notably, PA increased endoplasmic reticulum (ER) stress markers GRP78, PERK and CHOP, as well as enhanced the reactive oxygen species (ROS) content in adipocytes. These effects were accompanied by a reduction in cell viability and the induction of apoptosis. Interestingly, MPE and MSE counteracted PA-induced lipotoxicity by reducing ER stress markers and ROS production. In addition, MPE and MSE increased the level of the anti-oxidant transcription factor Nrf2 and its targets MnSOD and HO-1. Collectively, these results suggest that the intake of mango extract-enriched foods in association with a correct lifestyle could exert beneficial effects to counteract obesity. Full article
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21 pages, 5641 KiB  
Article
An Early and Sustained Inflammatory State Induces Muscle Changes and Establishes Obesogenic Characteristics in Wistar Rats Exposed to the MSG-Induced Obesity Model
by Matheus Felipe Zazula, Diego Francis Saraiva, João Lucas Theodoro, Mônica Maciel, Eliel Vieira dos Santos Sepulveda, Bárbara Zanardini de Andrade, Mariana Laís Boaretto, Jhyslayne Ignácia Hoff Nunes Maciel, Gabriela Alves Bronczek, Gabriela Moreira Soares, Sara Cristina Sagae Schneider, Gladson Ricardo Flor Bertolini, Márcia Miranda Torrejais, Lucinéia Fátima Chasko Ribeiro, Luiz Claudio Fernandes and Katya Naliwaiko
Int. J. Mol. Sci. 2023, 24(5), 4730; https://doi.org/10.3390/ijms24054730 - 01 Mar 2023
Cited by 3 | Viewed by 1394
Abstract
The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory [...] Read more.
The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG induction of obesity upon systemic and muscular parameters of Wistar rats. The animals were exposed to MSG subcutaneously (4 mg·g−1 b.w.) or saline (1.25 mg·g−1 b.w.) daily from PND01 to PND05 (n = 24). Afterwards, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, increased adiposity, and inducted hyperinsulinemia and a pro-inflammatory scenario. In adulthood, the following were observed: peripheral insulin resistance, increased fibrosis, oxidative distress, and a reduction in muscle mass, oxidative capacity, and neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty restoring in the muscle profile is related to the metabolic damage established early on. Full article
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10 pages, 270 KiB  
Article
Analysis of Selected Salivary Adipokines and Cytokines in Patients with Obesity—A Pilot Study
by Lucyna Ostrowska, Joanna Smarkusz-Zarzecka, Agnieszka Gornowicz, Karolina Lendzion, Beata Zyśk and Damian Pogodziński
Int. J. Mol. Sci. 2023, 24(4), 4145; https://doi.org/10.3390/ijms24044145 - 18 Feb 2023
Cited by 4 | Viewed by 1349
Abstract
Obesity is a chronic, progressive and relapsing disease that produces many adverse health, social and economic effects. The aim of the study was to analyse the concentrations of selected proinflammatory parameters in the saliva of obese and normal body weight individuals. The study [...] Read more.
Obesity is a chronic, progressive and relapsing disease that produces many adverse health, social and economic effects. The aim of the study was to analyse the concentrations of selected proinflammatory parameters in the saliva of obese and normal body weight individuals. The study included 116 people divided into two groups: the study group (n = 75, subjects with obesity) and the control group (n = 41, individuals with normal body weight). Bioelectrical impedance analysis was performed, and saliva samples were collected from all study participants to determine the concentrations of selected proinflammatory adipokines and cytokines. Statistically significantly higher concentrations of MMP-2, MMP-9 and IL-1β were found in the saliva of obese women compared to women with normal body weight. Furthermore, statistically significantly higher concentrations of MMP-9, IL-6 and resistin were observed in the saliva of obese men compared to men with normal body weight. Higher concentrations of selected proinflammatory cytokines and adipokines were found in the saliva of obese individuals compared to individuals with normal body weight. It is likely that higher concentrations of MMP-2, MMP-9 and IL-1β can be detected in the saliva of obese women compared to non-obese women, while higher concentrations of MMP-9, IL-6 and resistin can be found in the saliva of obese men compared to non-obese men, which suggests that further research to confirm our observations and determine the mechanisms of development of metabolic complications associated with obesity depending on gender is needed. Full article
13 pages, 2743 KiB  
Article
Long-Term Ingestion of Sicilian Black Bee Chestnut Honey and/or D-Limonene Counteracts Brain Damage Induced by High Fat-Diet in Obese Mice
by Simona Terzo, Pasquale Calvi, Domenico Nuzzo, Pasquale Picone, Mario Allegra, Flavia Mulè and Antonella Amato
Int. J. Mol. Sci. 2023, 24(4), 3467; https://doi.org/10.3390/ijms24043467 - 09 Feb 2023
Cited by 3 | Viewed by 1819
Abstract
Obesity is linked to neurodegeneration, which is mainly caused by inflammation and oxidative stress. We analyzed whether the long-term intake of honey and/or D-limonene, which are known for their antioxidant and anti-inflammatory actions, when ingested separately or in combination, can counteract the neurodegeneration [...] Read more.
Obesity is linked to neurodegeneration, which is mainly caused by inflammation and oxidative stress. We analyzed whether the long-term intake of honey and/or D-limonene, which are known for their antioxidant and anti-inflammatory actions, when ingested separately or in combination, can counteract the neurodegeneration occurring in high fat diet (HFD)-induced obesity. After 10 weeks of HFD, mice were divided into: HFD-, HFD + honey (HFD-H)-, HFD + D-limonene (HFD-L)-, HFD + honey + D-limonene (HFD-H + L)-fed groups, for another 10 weeks. Another group was fed a standard diet (STD). We analyzed the brain neurodegeneration, inflammation, oxidative stress, and gene expression of Alzheimer’s disease (AD) markers. The HFD animals showed higher neuronal apoptosis, upregulation of pro-apoptotic genes Fas-L, Bim P27 and downregulation of anti-apoptotic factors BDNF and BCL2; increased gene expression of the pro-inflammatory IL-1β, IL-6 and TNF-α and elevated oxidative stress markers COX-2, iNOS, ROS and nitrite. The honey and D-limonene intake counteracted these alterations; however, they did so in a stronger manner when in combination. Genes involved in amyloid plaque processing (APP and TAU), synaptic function (Ache) and AD-related hyperphosphorylation were higher in HFD brains, and significantly downregulated in HFD-H, HFD-L and HFD-H + L. These results suggest that honey and limonene ingestion counteract obesity-related neurodegeneration and that joint consumption is more efficacious than a single administration. Full article
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17 pages, 3785 KiB  
Article
Preliminary Evidence of the Potent and Selective Adenosine A2B Receptor Antagonist PSB-603 in Reducing Obesity and Some of Its Associated Metabolic Disorders in Mice
by Magdalena Kotańska, Anna Dziubina, Małgorzata Szafarz, Kamil Mika, Marek Bednarski, Noemi Nicosia, Ahmed Temirak, Christa E. Müller and Katarzyna Kieć-Kononowicz
Int. J. Mol. Sci. 2022, 23(21), 13439; https://doi.org/10.3390/ijms232113439 - 03 Nov 2022
Cited by 2 | Viewed by 1396
Abstract
The adenosine A2A and A2B receptors are promising therapeutic targets in the treatment of obesity and diabetes since the agonists and antagonists of these receptors have the potential to positively affect metabolic disorders. The present study investigated the link between body [...] Read more.
The adenosine A2A and A2B receptors are promising therapeutic targets in the treatment of obesity and diabetes since the agonists and antagonists of these receptors have the potential to positively affect metabolic disorders. The present study investigated the link between body weight reduction, glucose homeostasis, and anti-inflammatory activity induced by a highly potent and specific adenosine A2B receptor antagonist, compound PSB-603. Mice were fed a high-fat diet for 14 weeks, and after 12 weeks, they were treated for 14 days intraperitoneally with the test compound. The A1/A2A/A2B receptor antagonist theophylline was used as a reference. Following two weeks of treatment, different biochemical parameters were determined, including total cholesterol, triglycerides, glucose, TNF-α, and IL-6 blood levels, as well as glucose and insulin tolerance. To avoid false positive results, mouse locomotor and spontaneous activities were assessed. Both theophylline and PSB-603 significantly reduced body weight in obese mice. Both compounds had no effects on glucose levels in the obese state; however, PSB-603, contrary to theophylline, significantly reduced triglycerides and total cholesterol blood levels. Thus, our observations showed that selective A2B adenosine receptor blockade has a more favourable effect on the lipid profile than nonselective inhibition. Full article
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15 pages, 6381 KiB  
Article
Metabolic Syndrome Ameliorated by 4-Methylesculetin by Reducing Hepatic Lipid Accumulation
by Linghuan Li, Guangyao Zhu, Gaohang Fu, Weiwei Zha and Hanbing Li
Int. J. Mol. Sci. 2022, 23(18), 10465; https://doi.org/10.3390/ijms231810465 - 09 Sep 2022
Cited by 5 | Viewed by 1900
Abstract
Obesity is a chronic metabolic disease caused by an imbalance between energy intake and expenditure during a long period and is characterized by adipose tissue disfunction and hepatic steatosis. The aim of this study was to investigate the effect of 4-methylesculetin (4-ME), a [...] Read more.
Obesity is a chronic metabolic disease caused by an imbalance between energy intake and expenditure during a long period and is characterized by adipose tissue disfunction and hepatic steatosis. The aim of this study was to investigate the effect of 4-methylesculetin (4-ME), a coumarin derivative, upon adipose microenvironment and hepatic steatosis in mice induced by a high-fat diet (HFD), and to explore potential mechanisms of its beneficial effect on metabolic disorders. HFD-fed mice displayed visceral obesity, insulin resistance, and hepatic lipid accumulation, which was remarkably ameliorated by 4-ME treatment. Meanwhile, 4-ME ameliorated adipocyte hypertrophy, macrophage infiltration, hypoxia, and fibrosis in epididymal adipose tissue, thus improving the adipose tissue microenvironment. Furthermore, 4-ME reversed the increase in CD36, PPAR-γ, SREBP-1, and FASN, and the decrease in CPT-1A, PPAR-α, and Nrf2 translocation into the nucleus in livers of HFD mice and in FFA-incubated hepatocytes. Moreover, the beneficial effects of 4-ME upon lipid deposition and the expression of proteins related to lipid metabolism in FFA-induced LO2 cells were abolished by ML385, a specific Nrf2 inhibitor, indicating that Nrf2 is necessary for 4-ME to reduce hepatic lipid deposition. These findings suggested that 4-ME might be a potential lead compound candidate for preventing obesity and MAFLD. Full article
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13 pages, 1774 KiB  
Article
Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study
by Valentine Bordier, Fabienne Teysseire, Frank Senner, Götz Schlotterbeck, Jürgen Drewe, Christoph Beglinger, Bettina K. Wölnerhanssen and Anne Christin Meyer-Gerspach
Int. J. Mol. Sci. 2022, 23(17), 9867; https://doi.org/10.3390/ijms23179867 - 30 Aug 2022
Cited by 6 | Viewed by 2978
Abstract
The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy [...] Read more.
The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed. Full article
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26 pages, 7402 KiB  
Article
KSK-74: Dual Histamine H3 and Sigma-2 Receptor Ligand with Anti-Obesity Potential
by Kamil Mika, Małgorzata Szafarz, Monika Zadrożna, Barbara Nowak, Marek Bednarski, Katarzyna Szczepańska, Krzysztof Pociecha, Monika Kubacka, Noemi Nicosia, Izabela Juda, Katarzyna Kieć-Kononowicz and Magdalena Kotańska
Int. J. Mol. Sci. 2022, 23(13), 7011; https://doi.org/10.3390/ijms23137011 - 24 Jun 2022
Cited by 3 | Viewed by 1724
Abstract
Many studies involving compounds that enhance histamine release, such as histamine H3 receptor (H3R) antagonists, have shown efficacy in inhibiting weight gain, but none have passed clinical trials. As part of the search for H3 receptor ligands that have [...] Read more.
Many studies involving compounds that enhance histamine release, such as histamine H3 receptor (H3R) antagonists, have shown efficacy in inhibiting weight gain, but none have passed clinical trials. As part of the search for H3 receptor ligands that have additional properties, the aim of this study is to evaluate the activity in the reduction in weight gain in a rat model of excessive eating, as well as the impact on selected metabolic parameters, and the number and size of adipocytes of two new H3R antagonists, KSK-60 and KSK-74, which also exert a significant affinity at the sigma-2 receptor. Compounds KSK-60 and KSK-74 are homologues and the elongation of the distal part of the molecule resulted in an approximate two-fold reduction in affinity at H3R, but simultaneously an almost two-fold increase in affinity at the sigma-2 receptor. Animals fed palatable feed and receiving KSK-60 or KSK-74 both at 10 mg/kg b.w. gained significantly less weight than animals in the control obese group. Moreover, KSK-74 significantly compensated for metabolic disturbances that accompany obesity, such as an increase in plasma triglyceride, resistin, and leptin levels; improved glucose tolerance; and protected experimental animals against adipocyte hypertrophy. Furthermore, KSK-74 inhibited the development of inflammation in obesity-exposed adipose tissue. The in vivo pharmacological activity of the tested ligands appears to correlate with the affinity at the sigma-2 receptors; however, the explanation of this phenomenon requires further and extended research. Full article
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Review

Jump to: Editorial, Research

15 pages, 489 KiB  
Review
Overview of Curcumin and Piperine Effects on Glucose Metabolism: The Case of an Insulinoma Patient’s Loss of Consciousness
by Simona Servida, Elena Panzeri, Laura Tomaino, Giovanni Marfia, Emanuele Garzia, Giuseppe Ciniglio Appiani, Gianluca Moroncini, Vito De Gennaro Colonna, Carlo La Vecchia and Luisella Vigna
Int. J. Mol. Sci. 2023, 24(7), 6621; https://doi.org/10.3390/ijms24076621 - 01 Apr 2023
Cited by 2 | Viewed by 3246
Abstract
The hypoglycemic properties of curcumin supplements in therapeutic doses are well-known and may represent a useful tool for the treatment of chronic diseases such as metabolic syndrome, insulin resistance and type 2 diabetes. The poor bioavailability of curcumin can be improved with the [...] Read more.
The hypoglycemic properties of curcumin supplements in therapeutic doses are well-known and may represent a useful tool for the treatment of chronic diseases such as metabolic syndrome, insulin resistance and type 2 diabetes. The poor bioavailability of curcumin can be improved with the concomitant administration of piperine, with no severe adverse effects on glycemia reported so far in the literature. In this article, we further discuss a previously reported case of a helicopter pilot, affected by grade I obesity who, under curcumin and piperine treatment, experienced a transient loss of consciousness (TLOC), during a low-altitude flight. This episode led to a diagnosis of insulinoma, previously asymptomatic. We hypothesized that the combined effects of curcumin and piperine might have caused a severe hypoglycemic episode and subsequent TLOC. Therefore, further studies should be conducted to evaluate the safety of curcumin and piperine supplementation in subjects with impaired glucose metabolism and insulin secretion. Full article
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14 pages, 1181 KiB  
Review
Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment
by Sara Cruciani, Alessandro Palmerio Delitala, Maria Laura Cossu, Carlo Ventura and Margherita Maioli
Int. J. Mol. Sci. 2023, 24(3), 2310; https://doi.org/10.3390/ijms24032310 - 24 Jan 2023
Cited by 6 | Viewed by 3351
Abstract
Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and [...] Read more.
Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported. Full article
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17 pages, 873 KiB  
Review
Pathophysiological and Therapeutic Roles of Fascial Hyaluronan in Obesity-Related Myofascial Disease
by Chiedozie Kenneth Ugwoke, Erika Cvetko and Nejc Umek
Int. J. Mol. Sci. 2022, 23(19), 11843; https://doi.org/10.3390/ijms231911843 - 06 Oct 2022
Cited by 4 | Viewed by 2125
Abstract
Myofascial disease is an important complication associated with obesity and one of the leading causes of physical disability globally. In the face of limited treatment options, the burden of myofascial disorders is predicted to increase along with the escalating prevalence of obesity. Several [...] Read more.
Myofascial disease is an important complication associated with obesity and one of the leading causes of physical disability globally. In the face of limited treatment options, the burden of myofascial disorders is predicted to increase along with the escalating prevalence of obesity. Several pathological processes in obesity contribute to modifications in fascial extracellular matrix mechanical and biological properties and functions. Changes in adipose tissue metabolism, chronic inflammatory phenotype, oxidative stress, and other mechanisms in obesity may alter the physiochemical and biomechanical properties of fascial hyaluronan. Understanding the pathophysiological importance of hyaluronan and other components of the fascial connective tissue matrix in obesity may shed light on the etiology of associated myofascial disorders and inform treatment strategies. Given its unique and favorable pharmacological properties, hyaluronan has found a broad range of clinical applications, notably in orthopedic conditions such as osteoarthritis and tendinopathies, which share important pathophysiological mechanisms implicated in myofascial diseases. However, while existing clinical studies uniformly affirm the therapeutic value of hyaluronan in myofascial disorders, more extensive studies in broader pharmacological and clinical contexts are needed to firmly validate its therapeutic adaptation. Full article
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