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Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 46376

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Special Issue Editor

Dr. Anna M. Giudetti

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Department of Biological and Environmental Sciences and Technologies, University of Salento, 73047 Lecce, Italy
Interests: epithelial–mesenchymal transition; diabetes; lipid metabolism; mitochondrial carriers; obesity; thyroid hormones
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Changes in lifestyle and a shift from a traditional to an industrialized/westernized diet has drastically increased the rates of diet-related chronic disease. This has led to an unprecedented explosion in the prevalence of obesity and being overweight, cancers, and chronic and metabolic diseases.

The physiological mechanism of action of nutritional compounds is closely associated with their ability to recognize and modulate specific cellular enzymes or to affect the cell redox state. The identification of these targets is essential to recognize the mechanisms of action of nutritional compounds and their direct or indirect effects on cellular processes and functions in physiological and pathological conditions.

This Special Issue is dedicated to increasing and updating our knowledge about the association between dietary pattern and diet-related diseases. In particular, we intend to focus on the molecular, biochemical, and physiological processes underlying the mechanism of action of nutritional compounds and other dietary components. Studies aimed at characterising the chemical properties of nutrients and their analogues are also welcome. We look forward to significant contributions that will appeal to an international audience of researchers.

The following topics are of particular relevance and interest:

- The effects of nutrients on physiological functions and systems;

- The effects of nutrients in cellular reprogramming;

- The effects of nutrients on cellular and molecular processes;

- The effects of nutrients on energy homeostasis;

- The effects of nutrients on human diseases.

Dr. Anna M. Giudetti
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly 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 2900 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

Dietary nutrients
Human nutrition
Metabolic pathways
Human diseases
Mediterranean diet
Bioactive molecules
Signaling pathways
Analogues

Published Papers (10 papers)

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Research

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13 pages, 1559 KiB

Open AccessArticle

Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues

by Daniel Da Eira, Shailee Jani and Rolando B. Ceddia

Nutrients 2021, 13(10), 3357; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13103357 - 25 Sep 2021

Cited by 5 | Viewed by 3147

Abstract

Background: Obesity increases the severity of SARS-CoV-2 outcomes. Thus, this study tested whether obesogenic and ketogenic diets distinctly affect SARS-CoV-2 entry proteins and the renin-angiotensin system (RAS) in rat pulmonary and cardiac tissues. Methods: Male Sprague-Dawley rats were fed either standard chow (SC), a high-fat sucrose-enriched diet (HFS), or a ketogenic diet (KD) for 16 weeks. Afterwards, levels of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), RAS components, and inflammatory genes were measured in the lungs and hearts of these animals. Results: In the lungs, HFS elevated ACE2 and TMPRSS2 levels relative to SC diet, whereas the KD lowered the levels of these proteins and the gene expressions of toll-like receptor 4 and interleukin-6 receptor relative to HFS. The diets did not alter ACE2 and TMPRSS2 in the heart, although ACE2 was more abundant in heart than lung tissues. Conclusion: Diet-induced obesity increased the levels of viral entry proteins in the lungs, providing a mechanism whereby SARS-CoV-2 infectivity can be enhanced in obese individuals. Conversely, by maintaining low levels of ACE2 and TMPRSS2 and by exerting an anti-inflammatory effect, the KD can potentially attenuate the severity of infection and migration of SARS-CoV-2 to other ACE2-expressing tissues. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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11 pages, 1303 KiB

Open AccessArticle

Dampened Muscle mTORC1 Response Following Ingestion of High-Quality Plant-Based Protein and Insect Protein Compared to Whey

by Gommaar D’Hulst, Evi Masschelein and Katrien De Bock

Nutrients 2021, 13(5), 1396; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13051396 - 21 Apr 2021

Cited by 9 | Viewed by 6992

Abstract

Increased amino acid availability acutely stimulates protein synthesis partially via activation of mechanistic target of rapamycin complex 1 (mTORC1). Plant-and insect-based protein sources matched for total protein and/or leucine to animal proteins induce a lower postprandial rise in amino acids, but their effects on mTOR activation in muscle are unknown. C57BL/6J mice were gavaged with different protein solutions: whey, a pea–rice protein mix matched for total protein or leucine content to whey, worm protein matched for total protein, or saline. Blood was drawn 30, 60, 105 and 150 min after gavage and muscle samples were harvested 60 min and 150 min after gavage to measure key components of the mTORC1 pathway. Ingestion of plant-based proteins induced a lower rise in blood leucine compared to whey, which coincided with a dampened mTORC1 activation, both acutely and 150 min after administration. Matching total leucine content to whey did not rescue the reduced rise in plasma amino acids, nor the lower increase in mTORC1 compared to whey. Insect protein elicits a similar activation of downstream mTORC1 kinases as plant-based proteins, despite lower postprandial aminoacidemia. The mTORC1 response following ingestion of high-quality plant-based and insect proteins is dampened compared to whey in mouse skeletal muscle. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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17 pages, 10498 KiB

Open AccessArticle

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

by Adele Romano, Marzia Friuli, Laura Del Coco, Serena Longo, Daniele Vergara, Piero Del Boccio, Silvia Valentinuzzi, Ilaria Cicalini, Francesco P. Fanizzi, Silvana Gaetani and Anna M. Giudetti

Nutrients 2021, 13(2), 394; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020394 - 27 Jan 2021

Cited by 17 | Viewed by 2631

Abstract

Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by ¹H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg⁻¹ i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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21 pages, 9972 KiB

Open AccessArticle

In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular Surface

by Sung-Chul Hong, Jung-Heun Ha, Jennifer K. Lee, Sang Hoon Jung and Jin-Chul Kim

Nutrients 2020, 12(11), 3245; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12113245 - 23 Oct 2020

Cited by 13 | Viewed by 3553

Abstract

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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14 pages, 1768 KiB

Open AccessArticle

Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors

by Priscilla Biswas, Cinzia Dellanoce, Alessandra Vezzoli, Simona Mrakic-Sposta, Mauro Malnati, Alberto Beretta and Roberto Accinni

Nutrients 2020, 12(11), 3224; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12113224 - 22 Oct 2020

Cited by 17 | Viewed by 3973

Abstract

The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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19 pages, 2821 KiB

Open AccessArticle

The Effect of N-Acetylcysteine on Respiratory Enzymes, ADP/ATP Ratio, Glutathione Metabolism, and Nitrosative Stress in the Salivary Gland Mitochondria of Insulin Resistant Rats

by Anna Zalewska, Izabela Szarmach, Małgorzata Żendzian-Piotrowska and Mateusz Maciejczyk

Nutrients 2020, 12(2), 458; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020458 - 12 Feb 2020

Cited by 25 | Viewed by 3674

Abstract

This is the first study to assess the effect of N-acetylcysteine (NAC) on the mitochondrial respiratory system, as well as free radical production, glutathione metabolism, nitrosative stress, and apoptosis in the salivary gland mitochondria of rats with high-fat diet (HFD)-induced insulin resistance (IR). The study was conducted on male Wistar rats divided into four groups of 10 animals each: C (control, rats fed a standard diet containing 10.3% fat), C + NAC (rats fed a standard diet, receiving NAC intragastrically), HFD (rats fed a high-fat diet containing 59.8% fat), and HFD + NAC (rats fed HFD diet, receiving NAC intragastrically). We confirmed that 8 weeks of HFD induces systemic IR as well as disturbances in mitochondrial complexes of the parotid and submandibular glands of rats. NAC supplementation leads to a significant increase in the activity of complex I, II + III and cytochrome c oxidase (COX), and also reduces the ADP/ATP ratio compared to HFD rats. Furthermore, NAC reduces the hydrogen peroxide production/activity of pro-oxidant enzymes, increases the pool of mitochondrial glutathione, and prevents cytokine formation, apoptosis, and nitrosative damage to the mitochondria in both aforementioned salivary glands of HFD rats. To sum up, NAC supplementation enhances energy metabolism in the salivary glands of IR rats, and prevents inflammation, apoptosis, and nitrosative stress. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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13 pages, 4005 KiB

Open AccessArticle

Whether AICAR in Pregnancy or Lactation Prevents Hypertension Programmed by High Saturated Fat Diet: A Pilot Study

by Wan-Long Tsai, Chien-Ning Hsu and You-Lin Tain

Nutrients 2020, 12(2), 448; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020448 - 11 Feb 2020

Cited by 13 | Viewed by 2614

Abstract

High consumption of saturated fats links to the development of hypertension. AMP-activated protein kinase (AMPK), a nutrient-sensing signal, is involved in the pathogenesis of hypertension. We examined whether early intervention with a direct AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) during pregnancy or lactation can protect adult male offspring against hypertension programmed by high saturated fat consumption via regulation of nutrient sensing signals, nitric oxide (NO) pathway, and oxidative stress. Pregnant Sprague–Dawley rats received regular chow or high saturated fat diet (HFD) throughout pregnancy and lactation. AICAR treatment was introduced by intraperitoneal injection at 50 mg/kg twice a day for 3 weeks throughout the pregnancy period (AICAR/P) or lactation period (AICAR/L). Male offspring (n = 7–8/group) were assigned to five groups: control, HFD, AICAR/P, HFD + AICAR/L, and HFD + AICAR/P. Male offspring were killed at 16 weeks of age. HFD caused hypertension and obesity in male adult offspring, which could be prevented by AICAR therapy used either during pregnancy or lactation. As a result, we demonstrated that HFD downregulated AMPK/SIRT1/PGC-1α pathway in offspring kidneys. In contrast, AICAR therapy in pregnancy and, to a greater extent, in lactation activated AMPK signaling pathway. The beneficial effects of AICAR therapy in pregnancy is related to restoration of NO pathway. While AICAR uses in pregnancy and lactation both diminished oxidative stress induced by HFD. Our results highlighted that pharmacological AMPK activation might be a promising strategy to prevent hypertension programmed by excessive consumption of high-fat food. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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15 pages, 5045 KiB

Open AccessArticle

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

by Masayuki Izumi, Takashi Yoshida, Takashi Nakamura and Minoru Wakamori

Nutrients 2020, 12(2), 309; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020309 - 24 Jan 2020

Cited by 5 | Viewed by 3671

Abstract

Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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Review

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30 pages, 1159 KiB

Open AccessReview

The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

by Emily S. Krueger, Trevor S. Lloyd and Jeffery S. Tessem

Nutrients 2021, 13(8), 2873; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13082873 - 21 Aug 2021

Cited by 17 | Viewed by 5858

Abstract

Since elevated serum levels of trimethylamine N-oxide (TMAO) were first associated with increased risk of cardiovascular disease (CVD), TMAO research among chronic diseases has grown exponentially. We now know that serum TMAO accumulation begins with dietary choline metabolism across the microbiome-liver-kidney axis, which is typically dysregulated during pathogenesis. While CVD research links TMAO to atherosclerotic mechanisms in vascular tissue, its molecular effects on metabolic tissues are unclear. Here we report the current standing of TMAO research in metabolic disease contexts across relevant tissues including the liver, kidney, brain, adipose, and muscle. Since poor blood glucose management is a hallmark of metabolic diseases, we also explore the variable TMAO effects on insulin resistance and insulin production. Among metabolic tissues, hepatic TMAO research is the most common, whereas its effects on other tissues including the insulin producing pancreatic β-cells are largely unexplored. Studies on diseases including obesity, diabetes, liver diseases, chronic kidney disease, and cognitive diseases reveal that TMAO effects are unique under pathologic conditions compared to healthy controls. We conclude that molecular TMAO effects are highly context-dependent and call for further research to clarify the deleterious and beneficial molecular effects observed in metabolic disease research. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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21 pages, 2255 KiB

Open AccessReview

Preventive Role of L-Carnitine and Balanced Diet in Alzheimer’s Disease

by Alina Kepka, Agnieszka Ochocinska, Małgorzata Borzym-Kluczyk, Ewa Skorupa, Beata Stasiewicz-Jarocka, Sylwia Chojnowska and Napoleon Waszkiewicz

Nutrients 2020, 12(7), 1987; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12071987 - 03 Jul 2020

Cited by 38 | Viewed by 9087

Abstract

The prevention or alleviation of neurodegenerative diseases, including Alzheimer’s disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious disturbances in the functioning of the whole organism. The Mediterranean diet is characterized by a high consumption of fruits and vegetables, cereals, nuts, olive oil, and seeds as the major source of fats, moderate consumption of fish and poultry, low to moderate consumption of dairy products and alcohol, and low intake of red and processed meat. The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life. Full article

(This article belongs to the Special Issue Dietary Nutrients Effects on Metabolic and Physiological Adaptations: Mechanisms of Action in Health and Disease)

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