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Natural Products and Obesity
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Natural Products and Obesity

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

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 24134

Special Issue Editors

Dr. Saioa Gómez-Zorita

E-Mail Website
Guest Editor
1. Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy and Lucio Lascaray Research Center, University of the Basque Country (UPV/EHU), Vitoria, Spain
2. CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
3. BIOARABA Institute of Health, Vitoria-Gasteiz, Spain
Interests: obesity; liver steatosis; insulin resistance; bioactive compounds; mitochondria; autophagy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. María P. Portillo

E-Mail Website1 Website2
Guest Editor
1. Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy, Lucio Lascaray Research Center, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain
2. CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
3. BIOARABA Institute of Health, Vitoria-Gasteiz, Spain
Interests: molecular nutrition; nutritional and metabolic diseases; adipocytes; hepatocytes; lipogenesis; fat; inflammatory biomarkers; obesity; non-alcoholic fatty liver disease; insulin signaling; insulin; glucose metabolism; lipid metabolism; insulin resistance; adipogenesis; adipose tissue; liver
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Obesity is characterized by an excess of triacylglycerols, stored mainly in adipose tissue due to excess energy intake compared to energy expenditure. This disease is a major public health problem and can lead to complications such as hyperlipidemia, cerebrovascular diseases and cancer.

In recent years, it has been found that a variety of natural products are important sources of lead compounds, which can play an anti-obesity role by inhibiting adipose tissue formation, increasing adipose tissue thermogenesis and inducing white adipose tissue (WAT) browning. Phenolic acids, flavonoids, terpenoids and other natural products have various structures, beneficial activities and small toxic and side effects, which provide a basis for the development of new natural products for the treatment of obesity, and are an important source of anti-obesity drugs.

This special issue aims to collect papers on the molecular mechanisms of natural products in obesity treatment. Contributions are welcome in the form of research papers reporting original results or scientific reviews.

Importantly, the exact active ingredient of natural origin extract must be reported in the submitted research manuscript, since papers describing the effects of mixed extraction from natural origin are not in the scope of the journal.

Dr. Saioa Gómez-Zorita
Prof. Dr. María P. Portillo
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • natural products
  • obesity
  • brite adipocytes
  • white adipose tissue (WAT)
  • brown adipose tissue (BAT)
  • adipokines
  • browning

Published Papers (6 papers)

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Research

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22 pages, 10961 KiB  
Article
Cardamom (Elettaria cardamomum (L.) Maton) Seeds Intake Increases Energy Expenditure and Reduces Fat Mass in Mice by Modulating Neural Circuits That Regulate Adipose Tissue Lipolysis and Mitochondrial Oxidative Metabolism in Liver and Skeletal Muscle
by Claudia Delgadillo-Puga, Ivan Torre-Villalvazo, Yonatan Y. Cariño-Cervantes, Cinthia García-Luna, Paulina Soberanes-Chávez, Patricia de Gortari, Lilia G. Noriega, Claudia J. Bautista and Luis Cisneros-Zevallos
Int. J. Mol. Sci. 2023, 24(4), 3909; https://doi.org/10.3390/ijms24043909 - 15 Feb 2023
Cited by 1 | Viewed by 8705
Abstract
Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects [...] Read more.
Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects has not been studied. Here, we identified that EC modulates the neuroendocrine axis that regulates food intake, body weight, mitochondrial activity, and energy expenditure in mice. We fed C57BL/6 mice with diets containing 3%, 6%, or 12% EC or a control diet for 14 weeks. Mice fed the EC-containing diets gained less weight than control, despite slightly higher food intake. The lower final weight of EC-fed mice was due to lesser fat content but increased lean mass than control. EC intake increased lipolysis in subcutaneous adipose tissue, and reduced adipocyte size in subcutaneous, visceral, and brown adipose tissues. EC intake also prevented lipid droplet accumulation and increased mitochondrial content in skeletal muscle and liver. Accordingly, fasting and postprandial oxygen consumption, as well as fasting fat oxidation and postprandial glucose utilization were higher in mice fed with EC than in control. EC intake reduced proopiomelanocortin (POMC) mRNA content in the hypothalamic arcuate nucleus, without an impact on neuropeptide Y (NPY) mRNA. These neuropeptides control food intake but also influence the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. Thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and circulating triiodothyronine (T3) were lower in EC-fed mice than in control. This effect was linked with decreased circulating corticosterone and weight of adrenal glands. Our results indicate that EC modulates appetite, increases lipolysis in adipose tissue and mitochondrial oxidative metabolism in liver and skeletal muscle, leading to increased energy expenditure and lower body fat mass. These metabolic effects were ascribable to the modulation of the HPT and HPA axes. LC-MS profiling of EC found 11 phenolic compounds among which protocatechuic acid (23.8%), caffeic acid (21.06%) and syringic acid (29.25%) were the most abundant, while GC-MS profiling showed 16 terpenoids among which costunolide (68.11%), ambrial (5.3%) and cis-α-terpineol (7.99%) were identified. Extrapolation of mice-to-human EC intake was performed using the body surface area normalization equation which gave a conversion equivalent daily human intake dose of 76.9–308.4 mg bioactives for an adult of 60 kg that can be obtained from 14.5–58.3 g of cardamom seeds (18.5–74.2 g cardamom pods). These results support further exploration of EC as a coadjuvant in clinical practice. Full article
(This article belongs to the Special Issue Natural Products and Obesity)
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17 pages, 2426 KiB  
Article
Pomegranate Extract Augments Energy Expenditure Counteracting the Metabolic Stress Associated with High-Fat-Diet-Induced Obesity
by Marina Reguero, Marta Gómez de Cedrón, Aranzazu Sierra-Ramírez, Pablo José Fernández-Marcos, Guillermo Reglero, José Carlos Quintela and Ana Ramírez de Molina
Int. J. Mol. Sci. 2022, 23(18), 10460; https://doi.org/10.3390/ijms231810460 - 09 Sep 2022
Cited by 1 | Viewed by 1803
Abstract
Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, [...] Read more.
Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, precision nutrition may provide complementary approaches to target the metabolic alterations associated to “unhealthy obesity”. In a previous work, we described a pomegranate extract (PomE) rich in punicalagines to augment markers of browning and thermogenesis in human differentiated adipocytes and to augment the oxidative respiratory capacity in human differentiated myocytes. Herein, we have conducted a preclinical study of high-fat-diet (HFD)-induced obesity where PomE augments the systemic energy expenditure (EE) contributing to a reduction in the low grade of chronic inflammation and insulin resistance associated to obesity. At the molecular level, PomE promotes browning and thermogenesis in adipose tissue, reducing inflammatory markers and augmenting the reductive potential to control the oxidative stress associated to the HFD. PomE merits further investigation as a complementary approach to alleviate obesity, reducing the low grade of chronic inflammation and metabolic stress. Full article
(This article belongs to the Special Issue Natural Products and Obesity)
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17 pages, 12662 KiB  
Article
Structure–Activity Relationship of Synthetic Ginkgolic Acid Analogs for Treating Type 2 Diabetes by PTPN9 Inhibition
by Jinsoo Kim, Jinyoung Son, Dohee Ahn, Gibeom Nam, Xiaodi Zhao, Hyuna Park, Woojoo Jeong and Sang J. Chung
Int. J. Mol. Sci. 2022, 23(7), 3927; https://doi.org/10.3390/ijms23073927 - 01 Apr 2022
Cited by 4 | Viewed by 2271
Abstract
Ginkgolic acid (C13:0) (GA), isolated from Ginkgo biloba, is a potential therapeutic agent for type 2 diabetes. A series of GA analogs were designed and synthesized for the evaluation of their structure–activity relationship with respect to their antidiabetic effects. Unlike GA, the synthetic [...] Read more.
Ginkgolic acid (C13:0) (GA), isolated from Ginkgo biloba, is a potential therapeutic agent for type 2 diabetes. A series of GA analogs were designed and synthesized for the evaluation of their structure–activity relationship with respect to their antidiabetic effects. Unlike GA, the synthetic analog 1e exhibited improved inhibitory activity against PTPN9 and significantly stimulated glucose uptake via AMPK phosphorylation in differentiated 3T3-L1 adipocytes and C2C12 myotubes; it also induced insulin-dependent AKT activation in C2C12 myotubes in a concentration-dependent manner. Docking simulation results showed that 1e had a better binding affinity through a unique hydrophobic interaction with a PTPN9 hydrophobic groove. Moreover, 1e ameliorated palmitate-induced insulin resistance in C2C12 cells. This study showed that 1e increases glucose uptake and suppresses palmitate-induced insulin resistance in C2C12 myotubes via PTPN9 inhibition; thus, it is a promising therapeutic candidate for treating type 2 diabetes. Full article
(This article belongs to the Special Issue Natural Products and Obesity)
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Review

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14 pages, 1350 KiB  
Review
Anti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates
by Maitane González-Arceo, Iván Gomez-Lopez, Helen Carr-Ugarte, Itziar Eseberri, Marcela González, M. Pilar Cano, María P. Portillo and Saioa Gómez-Zorita
Int. J. Mol. Sci. 2023, 24(1), 299; https://doi.org/10.3390/ijms24010299 - 24 Dec 2022
Cited by 13 | Viewed by 1923
Abstract
Isorhamnetin is a plant-derived secondary metabolite which belongs to the family of flavonoids. This review summarises the main outcomes described in the literature to date, regarding the effects of isorhamnetin on obesity from in vitro and in vivo studies. The studies carried out [...] Read more.
Isorhamnetin is a plant-derived secondary metabolite which belongs to the family of flavonoids. This review summarises the main outcomes described in the literature to date, regarding the effects of isorhamnetin on obesity from in vitro and in vivo studies. The studies carried out in pre-adipocytes show that isorhamnetin is able to reduce adipogenesis at 10 μM or higher doses and that these effects are mediated by Pparγ and by Wnt signalling pathway. Very few studies addressed in rodents are available so far. It seems that treatment periods longer than two weeks are needed by isorhamnetin and its glycosides to be effective as anti-obesity agents. Nevertheless, improvements in glycaemic control can be observed even in short treatments. Regarding the underlying mechanisms of action, although some contradictory results have been found, reductions in de novo lipogenesis and fatty acid uptake could be proposed. Further research is needed to increase the scientific evidence referring to this topic; studies in animal models are essential, as well as randomised clinical trials to determine whether the positive results observed in animals could also be found in humans, in order to determine if isorhamnetin and its glycosides can represent a real tool against obesity. Full article
(This article belongs to the Special Issue Natural Products and Obesity)
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11 pages, 742 KiB  
Review
Ceramide Acyl Chain Length and Its Relevance to Intracellular Lipid Regulation
by Qing Wei Calvin Ho, Xiaofeng Zheng and Yusuf Ali
Int. J. Mol. Sci. 2022, 23(17), 9697; https://doi.org/10.3390/ijms23179697 - 26 Aug 2022
Cited by 20 | Viewed by 4011
Abstract
Ceramides are a class of sphingolipids which are implicated in skin disorders, obesity, and other metabolic diseases. As a class with pleiotropic effects, recent efforts have centred on discerning specific ceramide species and their effects on atopic dermatitis, obesity, type 2 diabetes, and [...] Read more.
Ceramides are a class of sphingolipids which are implicated in skin disorders, obesity, and other metabolic diseases. As a class with pleiotropic effects, recent efforts have centred on discerning specific ceramide species and their effects on atopic dermatitis, obesity, type 2 diabetes, and cardiovascular diseases. This delineation has allowed the identification of disease biomarkers, with long acyl chain ceramides such as C16- and C18-ceramides linked to metabolic dysfunction and cardiac function decline, while ultra-long acyl chain ceramides (>25 carbon acyl chain) were reported to be essential for maintaining a functional skin barrier. Given the intricate link between free fatty acids with ceramides, especially the de novo synthetic pathway, intracellular lipid droplet formation is increasingly viewed as an important mechanism for preventing accumulation of toxic ceramide species. Here, we review recent reports of various ceramide species involved in skin abnormalities and metabolic diseases, and we propose that promotion of lipid droplet biogenesis can be seen as a potential protective mechanism against deleterious ceramides. Full article
(This article belongs to the Special Issue Natural Products and Obesity)
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26 pages, 2249 KiB  
Review
Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action
by Henrique J. C. B. Gouveia, Mercedes V. Urquiza-Martínez, Raul Manhães-de-Castro, Bárbara J. R. Costa-de-Santana, José Pérez Villarreal, Rosalío Mercado-Camargo, Luz Torner, Jailane de Souza Aquino, Ana E. Toscano and Omar Guzmán-Quevedo
Int. J. Mol. Sci. 2022, 23(15), 8344; https://doi.org/10.3390/ijms23158344 - 28 Jul 2022
Cited by 22 | Viewed by 4499
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, [...] Read more.
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids. Full article
(This article belongs to the Special Issue Natural Products and Obesity)
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