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Diet and Metabolism: Molecular Mechanisms of Health and Disease

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 30171

Special Issue Editors

Istituto per l’Endocrinologia e l’Oncologia Sperimentale “G. Salvatore” (IEOS), CNR, 80131 Naples, Italy
Interests: stem cells; cancer stem cells; carcinogenesis; glioblastoma; high mobility group proteins; asymmetric division; diet; adipose tissue; obesity; differentiation
Special Issues, Collections and Topics in MDPI journals
MD Anderson Cancer Center, Dept. Genomic Medicine, Houston, TX
Interests: metabolism; cancer biology; brain cancer; cancer metabolism; lipid metabolism

Special Issue Information

Dear Colleagues,

Nutrients are, by definition, the building blocks for energy generation and tissue homeostasis. The plethora of coordinated pathways that define their molecular fate altogether constitute our metabolism. In the last decades, metabolic alterations, caused by poor eating habits or congenital mutations, have emerged to dramatically affect human health and to foster the onset of diseases such as cardiovascular disease, diabetes, and cancer.

This Special issue calls for original articles, reviews, and perspectives addressing, but not limited to, the following:

  • the beneficial and detrimental impact of diet on human health
  • nutrients’ effect on stem cells, including cancer stem cells
  • the importance of diet in cancer prevention and response to therapies
  • the molecular mechanisms underlying tumor cellular metabolism
  • the molecular effects of caloric restriction and obesity
  • the role of diet and metabolism in immunity and autoimmune diseases
  • the action of dietary bioactive compounds
  • the crosstalk between the metabolism and microbiome
  • metabolism and cardiovascular disease, insulin resistance, and diabetes

Dr. Sabrina Battista
Dr. Francesca Puca
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

  • diet
  • metabolism
  • nutrients
  • stem cell
  • cancer stem cell
  • cancer metabolism
  • bioactive compounds
  • glucose
  • lipids
  • obesity
  • caloric restriction
  • high fat diet
  • cardiovascular disease
  • diabetes
  • oxygen
  • hypoxia
  • immune system
  • microbiota
  • autoimmune disease
  • insulin resistance
  • nutraceutics
  • cancer prevention
  • tumor cell metabolism
  • biosynthesis
  • energy
  • glycolysis
  • carbohydrates
  • amino acids
  • homeostasis
  • sirtuins
  • mTOR
  • exercise

Published Papers (8 papers)

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Research

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21 pages, 5083 KiB  
Article
Drosophila Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
Int. J. Mol. Sci. 2021, 22(22), 12424; https://doi.org/10.3390/ijms222212424 - 17 Nov 2021
Cited by 2 | Viewed by 1856
Abstract
The small intestine is the initial site of glucose absorption and thus represents the first of a continuum of events that modulate normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in [...] Read more.
The small intestine is the initial site of glucose absorption and thus represents the first of a continuum of events that modulate normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. Using molecular genetic approaches, we investigated the role of Drosophila Solute Carrier 5A5 (dSLC5A5) in regulating glucose homeostasis by mediating glucose uptake in the fly midgut. By genetically knocking down dSLC5A5 in flies, we found that systemic and circulating glucose and trehalose levels are significantly decreased, which correlates with an attenuation in glucose uptake in the enterocytes. Reciprocally, overexpression of dSLC5A5 significantly increases systemic and circulating glucose and trehalose levels and promotes glucose uptake in the enterocytes. We showed that dSLC5A5 undergoes apical endocytosis in a dynamin-dependent manner, which is essential for glucose uptake in the enterocytes. Furthermore, we showed that the dSLC5A5 level in the midgut is upregulated by glucose and that dSLC5A5 critically directs systemic glucose homeostasis on a high-sugar diet. Together, our studies have uncovered the first Drosophila glucose transporter in the midgut and revealed new mechanisms that regulate glucose transporter levels and activity in the enterocyte apical membrane. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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12 pages, 2621 KiB  
Article
Restriction of Manganese Intake Prevents the Onset of Brain Manganese Overload in Zip14−/− Mice
Int. J. Mol. Sci. 2021, 22(13), 6773; https://doi.org/10.3390/ijms22136773 - 24 Jun 2021
Cited by 5 | Viewed by 1615
Abstract
As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess [...] Read more.
As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess manganese in the body primarily affects the central nervous system, resulting in irreversible neurological disorders. Therefore, to prevent the onset of brain manganese accumulation becomes critical. In this study, we used Zip14−/− mice as a model for ZIP14 deficiency and discovered that these mice were born without manganese loading in the brain, but started to hyper-accumulate manganese within 3 weeks after birth. We demonstrated that decreasing manganese intake in Zip14−/− mice was effective in preventing manganese overload that typically occurs in these animals. Our results provide important insight into future studies that are targeted to reduce the onset of manganese accumulation associated with ZIP14 dysfunction in humans. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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Review

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28 pages, 4664 KiB  
Review
Role of Diet in Stem and Cancer Stem Cells
Int. J. Mol. Sci. 2022, 23(15), 8108; https://doi.org/10.3390/ijms23158108 - 23 Jul 2022
Cited by 9 | Viewed by 3788
Abstract
Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells’ functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties [...] Read more.
Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells’ functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties result from the complex integration of intrinsic, extrinsic, and systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem cell fate determination, lineage specification and differentiation. The purpose of this review is to provide a comprehensive description of the multiple “non-metabolic” effects of diet on stem cell functions, including little-known effects such as those on liquid-liquid phase separation and on non-random chromosome segregation (asymmetric division). A deep understanding of the specific dietetic requirements of normal and cancer stem cells may pave the way for the development of nutrition-based targeted therapeutic approaches to improve regenerative and anticancer therapies. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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16 pages, 937 KiB  
Review
Obesity and Male Reproduction: Do Sirtuins Play a Role?
Int. J. Mol. Sci. 2022, 23(2), 973; https://doi.org/10.3390/ijms23020973 - 16 Jan 2022
Cited by 9 | Viewed by 3324
Abstract
Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the [...] Read more.
Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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20 pages, 403 KiB  
Review
Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy
Int. J. Mol. Sci. 2021, 22(21), 11687; https://doi.org/10.3390/ijms222111687 - 28 Oct 2021
Cited by 37 | Viewed by 5648
Abstract
Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statin-therapy-mediated positive effects on cardiovascular events, patient [...] Read more.
Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statin-therapy-mediated positive effects on cardiovascular events, patient compliance is often poor. Statin-associated muscle symptoms (SAMS) are the most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate muscle pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, are reported by 10% to 25% of patients receiving statin therapy. There are many risk factors associated with patient features and hypolipidemic agents that seem to increase the risk of developing SAMS. Due to the lack of a “gold standard”, the diagnostic test for SAMS is based on a clinical criteria score, which is independent of creatine kinase (CK) elevation. Mechanisms that underlie the pathogenesis of SAMS remain almost unclear, though a high number of risk factors may increase the probability of myotoxicity induced by statin therapy. Some of these, related to pharmacokinetic properties of statins and to concomitant therapies or patient characteristics, may affect statin bioavailability and increase vulnerability to high-dose statins. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
30 pages, 2178 KiB  
Review
Insulin Resistance and Cancer: In Search for a Causal Link
Int. J. Mol. Sci. 2021, 22(20), 11137; https://doi.org/10.3390/ijms222011137 - 15 Oct 2021
Cited by 38 | Viewed by 6655
Abstract
Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes [...] Read more.
Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes mellitus, and cancer. Although the underlying mechanism(s) for this association remain unclear, it is well established that hyperinsulinemia, a hallmark of IR, may play a role in tumorigenesis. On the other hand, IR is strongly associated with visceral adiposity dysfunction and systemic inflammation, two conditions which favor the establishment of a pro-tumorigenic environment. Similarly, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA, in IR states, have been often associated with tumorigenesis in numerous types of human cancer. In addition to these observations, it is also broadly accepted that gut microbiota may play an intriguing role in the development of IR-related diseases, including type 2 diabetes and cancer, whereas potential chemopreventive properties have been attributed to some of the most commonly used antidiabetic medications. Herein we provide a concise overview of the most recent literature in this field and discuss how different but interrelated molecular pathways may impact on tumor development. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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12 pages, 1202 KiB  
Review
Epithelial Cell Transformation and Senescence as Indicators of Genome Aging: Current Advances and Unanswered Questions
Int. J. Mol. Sci. 2021, 22(14), 7544; https://doi.org/10.3390/ijms22147544 - 14 Jul 2021
Cited by 2 | Viewed by 2071
Abstract
The recent advances in deciphering the human genome allow us to understand and evaluate the mechanisms of human genome age-associated transformations, which are largely unclear. Genome sequencing techniques assure comprehensive mapping of human genetics; however, understanding of gene functional interactions, specifically of time/age-dependent [...] Read more.
The recent advances in deciphering the human genome allow us to understand and evaluate the mechanisms of human genome age-associated transformations, which are largely unclear. Genome sequencing techniques assure comprehensive mapping of human genetics; however, understanding of gene functional interactions, specifically of time/age-dependent modifications, remain challenging. The age of the genome is defined by the sum of individual (inherited) and acquired genomic traits, based on internal and external factors that impact ontogenesis from the moment of egg fertilization and embryonic development. The biological part of genomic age opens a new perspective for intervention. The discovery of single cell-based mechanisms for genetic change indicates the possibility of influencing aging and associated disease burden, as well as metabolism. Cell populations with transformed genetic background were shown to serve as the origin of common diseases during extended life expectancy (superaging). Consequently, age-related cell transformation leads to cancer and cell degeneration (senescence). This article aims to describe current advances in the genomic mechanisms of senescence and its role in the spatiotemporal spread of epithelial clones and cell evolution. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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13 pages, 2662 KiB  
Review
Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer
Int. J. Mol. Sci. 2021, 22(14), 7278; https://doi.org/10.3390/ijms22147278 - 06 Jul 2021
Cited by 5 | Viewed by 3033
Abstract
One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle. These include nucleotide synthesis; the methylation of DNA, RNA, and proteins in the methionine cycle; and transsulfuration to maintain the redox condition of cancer stem cells in the [...] Read more.
One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle. These include nucleotide synthesis; the methylation of DNA, RNA, and proteins in the methionine cycle; and transsulfuration to maintain the redox condition of cancer stem cells in the tumor microenvironment. Recent studies have indicated that small therapeutic compounds affect the mitochondrial folate cycle, epitranscriptome (RNA methylation), and reactive oxygen species reactions in cancer cells. The epitranscriptome controls cellular biochemical reactions, but is also a platform for cell-to-cell interaction and cell transformation. We present an update of recent advances in the study of 1C metabolism related to cancer and demonstrate the areas where further research is needed. We also discuss approaches to therapeutic drug discovery using animal models and propose further steps toward developing precision cancer medicine. Full article
(This article belongs to the Special Issue Diet and Metabolism: Molecular Mechanisms of Health and Disease)
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