Special Issue "Perspective of Metabolism: Potential Therapeutic Targets of Metabolic Diseases such as Obesity-Associated Diabetes, Atherosclerosis and Fatty Liver"

A special issue of Medicines (ISSN 2305-6320). This special issue belongs to the section "Endocrinology and Metabolic Disorders".

Deadline for manuscript submissions: 31 December 2022 | Viewed by 15163

Special Issue Editor

Dr. Abhishek Singh
E-Mail Website
Guest Editor
Pharmacology, School of Medicine, Yale university, New Haven, Connecticut, USA
Interests: lipid and glucose metabolism; atherosclerosis; diabetes; muscle atrophy; NAFLD; NASH; obesity

Special Issue Information

Dear Colleagues,

Preclinical and clinical studies have shown that elevated levels of triglyceride-rich lipoproteins (TRL) and their remnant particles are associated with the development of type 2 diabetes (T2D), coronary atherosclerosis, and fatty liver. Under normal physiological conditions, triacylglycerol (TAG) is transported through the bloodstream in circulating TRL, including chylomicrons and very-low-density lipoproteins (VLDL). TRL is hydrolyzed into free fatty acids (FFA) and glycerol by the lipoprotein lipase (LPL) in the capillary beds of many tissues, especially adipose, cardiac, and skeletal muscle where LPL releases the TAGs for intracellular storage or energy production.

The imbalance between dyslipidemia (high levels of circulating TAGs and cholesterol) and ectopic lipid accumulation is critical in metabolic homeostasis. While reducing circulating lipids could help to prevent cardiovascular diseases such as atherosclerosis, excessive accumulation of lipids in tissues can lead to lipotoxicity and insulin resistance (IR). Therefore, the management of the serum lipoprotein profile could be an effective potential therapeutic target for the treatment of metabolic diseases. For this Special Issue, we invite articles related to a metabolic pathway based on lipid and glucose metabolism that reveal therapeutic targets against cardio-metabolic disease.

Dr. Abhishek Singh
Guest Editor

Manuscript Submission Information

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Keywords

  • obesity
  • diabetes
  • atherosclerosis
  • muscle atrophy
  • liver disease
  • nonalcoholic fatty liver disease (NAFLD)
  • nonalcoholic steatohepatitis (NASH)
  • therapies
  • lipoprotein-lipid metabolism
  • glucose homeostasis
  • cardiometabolism

Published Papers (10 papers)

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Research

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Article
Early Time-Restricted Feeding Amends Circadian Clock Function and Improves Metabolic Health in Male and Female Nile Grass Rats
Medicines 2022, 9(2), 15; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines9020015 - 21 Feb 2022
Viewed by 1008
Abstract
Lengthening the daily eating period contributes to the onset of obesity and metabolic syndrome. Dietary approaches, including energy restriction and time-restricted feeding, are promising methods to combat metabolic disorders. This study explored the effect of early and late time-restricted feeding (TRF) on weight [...] Read more.
Lengthening the daily eating period contributes to the onset of obesity and metabolic syndrome. Dietary approaches, including energy restriction and time-restricted feeding, are promising methods to combat metabolic disorders. This study explored the effect of early and late time-restricted feeding (TRF) on weight and adiposity, food consumption, glycemic control, clock gene expression, and liver metabolite composition in diurnal Nile grass rats (NGRs). Adult male and female Nile grass rats were randomly assigned to one of three groups: (1) access to a 60% high-fat (HF) diet ad-libitum (HF-AD), (2) time-restricted access to the HF diet for the first 6 h of the 12 h light/active phase (HF-AM) or (3) the second 6 h of the 12 h light/active phase (HF-PM). Animals remained on their respective protocols for six weeks. TRF reduced total energy consumption and weight gain, and early TRF (HF-AM) reduced fasting blood glucose, restored Per1 expression, and reduced liver lipid levels. Although sex-dependent differences were observed for fat storage and lipid composition, TRF improved metabolic parameters in both male and female NGRs. In conclusion, this study demonstrated that early TRF protocol benefits weight management, improves lipid and glycemic control, and restores clock gene expression in NGRs. Full article
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Article
Effect of Breastfeeding and Its Duration on Impaired Fasting Glucose and Diabetes in Perimenopausal and Postmenopausal Women: Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2019
Medicines 2021, 8(11), 71; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8110071 - 12 Nov 2021
Viewed by 927
Abstract
Background and Objectives: To examine the effect of maternal breastfeeding on the subsequent risk of diabetes in parous Korean women aged >50 years. Materials and Methods: A total of 14,433 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) were included. [...] Read more.
Background and Objectives: To examine the effect of maternal breastfeeding on the subsequent risk of diabetes in parous Korean women aged >50 years. Materials and Methods: A total of 14,433 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) were included. The subjects were divided into three groups: normal, impaired fasting glucose, and diabetes. The adjusted odds ratios (ORs) for impaired fasting glucose (IFG) and diabetes were assessed using multivariate logistic regression. Results: A total of 2301 (15.94%) women were classified as having diabetes, and 3670 (25.43%) women were classified as having impaired fasting glucose. Breastfeeding was associated with an OR for diabetes of 0.76 (95% confidence interval (CI): 0.61, 0.95) compared with non-breastfeeding after adjustment for possible confounders in the multivariable logistic regression analysis. Breastfeeding for 13–24 months was associated with an OR of 0.68 (95% CI, 0.5, 0.91), and breastfeeding for 25–36 months was associated with an OR of 0.68 (95% CI, 0.52, 0.87) for diabetes compared with breastfeeding for <1 month in the multivariable logistic regression analysis. Conclusions: Our results suggest that long-term breastfeeding, particularly breastfeeding for 13–36 months, may be associated with a lower risk for diabetes later in life. Full article
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Article
Recent Trends of Metabolic Syndrome and Its Components in Military Recruits from Saudi Arabia
Medicines 2021, 8(11), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8110065 - 30 Oct 2021
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Abstract
Metabolic syndrome (Met-S) constitutes the risk factors and abnormalities that markedly increase the probability of developing diabetes and coronary heart disease. An early detection of Met-S, its components and risk factors can be of great help in preventing or controlling its adverse consequences. [...] Read more.
Metabolic syndrome (Met-S) constitutes the risk factors and abnormalities that markedly increase the probability of developing diabetes and coronary heart disease. An early detection of Met-S, its components and risk factors can be of great help in preventing or controlling its adverse consequences. The aim of the study was to determine the prevalence of cardio-metabolic risk factors in young army recruits from Saudi Arabia. A total of 2010 Saudis aged 18–30 years were randomly selected from groups who had applied to military colleges. In addition to designed questionnaire, anthropometric measurements and blood samples were collected to measure Met-S components according to the International Diabetes Federation (IDF) criteria. Met-S prevalence was 24.3% and it was higher in older subjects than the younger ones. There were significant associations between Met-S and age, education level and marital status. The most common Met-S components were high fasting blood sugar (63.6%) followed by high blood pressure (systolic and diastolic, 63.3% and 37.3% respectively) and high body mass index (57.5%). The prevalence of pre-diabetes and diabetes were found to be 55.2% and 8.4%, respectively. Hypertriglyceridemia was found in 19.3% and low levels of high-density lipoproteins (HDL) in 11.7% of subjects. In conclusion, there is a high prevalence of Met-S in young adults of Saudi Arabia. There is a need for regular monitoring of Met-S in young populations to keep them healthy and fit for nation building. It is also important to design and launch community-based programs for educating people about the importance of physical activity, cessation of smoking and eating healthy diet in prevention of chronic diseases. Full article
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Communication
Anti-Inflammatory Effects of Morinda citrifolia Extract against Lipopolysaccharide-Induced Inflammation in RAW264 Cells
Medicines 2021, 8(8), 43; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080043 - 04 Aug 2021
Cited by 1 | Viewed by 1675
Abstract
Leaves of Morinda citrifolia (noni) have been used in Polynesian folk medicine for the treatment of pain and inflammation, and their juice is very popular worldwide as a functional food supplement. This study aimed to demonstrate that M. citrifolia seed extract exerts anti-inflammatory [...] Read more.
Leaves of Morinda citrifolia (noni) have been used in Polynesian folk medicine for the treatment of pain and inflammation, and their juice is very popular worldwide as a functional food supplement. This study aimed to demonstrate that M. citrifolia seed extract exerts anti-inflammatory effects on RAW264 cells stimulated by lipopolysaccharide. To confirm the inhibitory effect of M. citrifolia seed extract, we assessed the production of nitric oxide (NO) and inflammatory cytokines. The M. citrifolia seed extract showed a significant inhibition of NO production, with no effect on cell viability, and was more active than M. citrifolia seed oil, leaf extract, and fruit extract. The M. citrifolia seed extract was found to reduce the expression of inducible NO synthase and tumor necrosis factor-alpha of pro-inflammatory cytokines. These results suggest that the anti-inflammatory effect of M. citrifolia seed extract is related to a reduction in the expression of inflammatory mediators and support its potential therapeutic use. Full article
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Article
Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance
Medicines 2021, 8(7), 34; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8070034 - 01 Jul 2021
Cited by 1 | Viewed by 2162
Abstract
Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per–Arnt–Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK−/−) protects against triglyceride accumulation, insulin resistance, and weight gain on [...] Read more.
Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per–Arnt–Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK−/−) protects against triglyceride accumulation, insulin resistance, and weight gain on a high-fat diet; conditions that are associated with dysbiosis of the gut microbiome. Methods: Herein, we report the metabolic effects of the interplay of diet (high fat high sugar, HFHS), genotype (PASK−/−), and microbiome (16S sequencing). Results: Microbiome analysis identified a diet-induced, genotype-independent forked shift, with two discrete clusters of HFHS mice having increased beta and decreased alpha diversity. A “lower” cluster contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres, and was associated with increased weight gain, glucose intolerance, triglyceride accumulation, and decreased claudin-1 expression. Genotypic effects were observed within the clusters, lower cluster PASK−/− mice displayed increased weight gain and decreased triglyceride accumulation, whereas upper PASK−/− were resistant to decreased claudin-1. Conclusions: These results confirm previous reports that PAS kinase deficiency can protect mice against the deleterious effects of diet, and they suggest that microbiome imbalances can override protection. In addition, these results support a healthy diet for beneficial microbiome maintenance and suggest microbial culprits associated with metabolic disease. Full article
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Article
The Role of Poly-Herbal Extract in Sodium Chloride-Induced Oxidative Stress and Hyperlipidemia in Male Wistar Rats
Medicines 2021, 8(6), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8060025 - 31 May 2021
Cited by 3 | Viewed by 2169
Abstract
Consistent consumption of high salt diet (HSD) has been associated with increased cellular generation of free radicals, which has been implicated in the derangement of some vital organs and etiology of cardiovascular disorders. This study was designed to investigate the combined effect of [...] Read more.
Consistent consumption of high salt diet (HSD) has been associated with increased cellular generation of free radicals, which has been implicated in the derangement of some vital organs and etiology of cardiovascular disorders. This study was designed to investigate the combined effect of some commonly employed medicinal plants on serum lipid profile and antioxidant status of aorta, kidney, and liver of high salt diet-fed animals. Out of the total fifty male Wistar rats obtained, fifteen were used for acute toxicity study, while the remaining thirty-five were divided into 5 groups of 7 animals each. Group 1 and 2 animals were fed normal rat chow (NRC) and 16% high salt diet (HSD) only, respectively. Animals in groups 3, 4 and 5 were fed 16% HSD with 800, 400, and 200 mg/kg bw poly-herbal extract (PHE), respectively, once for 28 consecutive days. Serum low-density lipoprotein (LDL), triacylglycerol (TG), total cholesterol (TC) and high-density lipoprotein (HDL), malondialdehyde, nitric oxide, catalase, superoxide dismutase, glutathione peroxidase, glutathione concentration, and activities were assessed in the aorta, kidney, and liver. Poly-herbal extract (p < 0.05) significantly reduced malondialdehyde and nitric oxide concentrations and also increased antioxidant enzymes and glutathione activity. Elevated serum TG, TC, LDL, and TC content in HSD-fed animals were significantly (p < 0.05) reduced to normal in PHE-treated rats while HDL was significantly elevated (p < 0.05) in a concentration-dependent manner in PHE treated animals. Feeding with PHE attenuated high-salt diet imposed derangement in serum lipid profile and antioxidant status in the organs of the experimental rats. Full article
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Review

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Review
Salubrious Effects of Green Tea Catechins on Fatty Liver Disease: A Systematic Review
Medicines 2022, 9(3), 20; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines9030020 - 01 Mar 2022
Viewed by 1002
Abstract
Epigallocatechin-3-gallate (EGCG) is a polyphenol green tea catechin with potential health benefits and therapeutic effects in non-alcoholic fatty liver disease (NAFLD), a common liver disorder that adversely affects liver function and lipid metabolism. This systematic review surveyed the effects of EGCG or green [...] Read more.
Epigallocatechin-3-gallate (EGCG) is a polyphenol green tea catechin with potential health benefits and therapeutic effects in non-alcoholic fatty liver disease (NAFLD), a common liver disorder that adversely affects liver function and lipid metabolism. This systematic review surveyed the effects of EGCG or green tea extract (GTE) on NAFLD reported in studies involving rodent models or humans with a focus on clinicopathologic outcomes, lipid and carbohydrate metabolism, and inflammatory, oxidative stress, and liver injury markers. Articles involving clinical efficacy of EGCG/GTE on human subjects and rodent models were gathered by searching the PUBMED database and by referencing additional articles identified from other literature reviews. EGCG or GTE supplementation reduced body weight, adipose tissue deposits, and food intake. Mechanistically, the majority of these studies confirmed that EGCG or GTE supplementation plays a significant role in regulating lipid and glucose metabolism and expression of genes involved in lipid synthesis. Importantly, EGCG and GTE supplementation were shown to have beneficial effects on oxidative stress-related pathways that activate pro-inflammatory responses, leading to liver damage. In conclusion, green tea catechins are a potentially useful treatment option for NAFLD. More research is required to determine the ideal dosage, treatment duration, and most effective delivery method of EGCG or GTE, and to provide more definitive conclusions by performing large, randomized clinical trials. Full article
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Review
Exercise, Diet and Sleeping as Regenerative Medicine Adjuvants: Obesity and Ageing as Illustrations
Medicines 2022, 9(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines9010007 - 14 Jan 2022
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Abstract
Regenerative medicine uses the biological and medical knowledge on how the cells and tissue regenerate and evolve in order to develop novel therapies. Health conditions such as ageing, obesity and cancer lead to an impaired regeneration ability. Exercise, diet choices and sleeping pattern [...] Read more.
Regenerative medicine uses the biological and medical knowledge on how the cells and tissue regenerate and evolve in order to develop novel therapies. Health conditions such as ageing, obesity and cancer lead to an impaired regeneration ability. Exercise, diet choices and sleeping pattern have significant impacts on regeneration biology via diverse pathways including reducing the inflammatory and oxidative components. Thus, exercise, diet and sleeping management can be optimized towards therapeutic applications in regenerative medicine. It could allow to prevent degeneration, optimize the biological regeneration and also provide adjuvants for regenerative medicine. Full article
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Other

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Opinion
Impact of Adiposity and Fat Distribution, Rather Than Obesity, on Antibodies as an Illustration of Weight-Loss-Independent Exercise Benefits
Medicines 2021, 8(10), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8100057 - 08 Oct 2021
Cited by 4 | Viewed by 1237
Abstract
Obesity represents a risk factor for a variety of diseases because of its inflammatory component, among other biological patterns. Recently, with the ongoing COVID-19 crisis, a special focus has been put on obesity as a status in which antibody production, among other immune [...] Read more.
Obesity represents a risk factor for a variety of diseases because of its inflammatory component, among other biological patterns. Recently, with the ongoing COVID-19 crisis, a special focus has been put on obesity as a status in which antibody production, among other immune functions, is impaired, which would impact both disease pathogenesis and vaccine efficacy. Within this piece of writing, we illustrate that such patterns would be due to the increased adiposity and fat distribution pattern rather than obesity (as defined by the body mass index) itself. Within this context, we also highlight the importance of the weight-loss-independent effects of exercise. Full article
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Case Report
Advances in the Treatment of Gastrointestinal Bleeding: Safety and Efficiency of Transnasal Endoscopy
Medicines 2021, 8(9), 53; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8090053 - 14 Sep 2021
Cited by 1 | Viewed by 1698
Abstract
Acute upper gastrointestinal bleeding (UGIB) is a common disorder and a gastroenterological emergency. With the development of new techniques and devices, the survivability after gastrointestinal bleeding is improving. However, at the same time, we are facing the difficulty of severely complicated cases with [...] Read more.
Acute upper gastrointestinal bleeding (UGIB) is a common disorder and a gastroenterological emergency. With the development of new techniques and devices, the survivability after gastrointestinal bleeding is improving. However, at the same time, we are facing the difficulty of severely complicated cases with various diseases. For example, while endoscopic examination with a normal diameter endoscope is essential for the diagnosis and treatment of UGIB, there are several cases in which it cannot be used. In these cases, transnasal endoscopy (TNE) may be a viable treatment option. This report reviews current hemostatic devices for endoscopic treatment and the safety and efficiency of using TNE in complicated cases. The latter will be demonstrated in a case report where TNE was employed in a patient with severe esophageal stenosis. This review summarizes the advances made in the devices used and will provide further ideas for the physician in terms of combining these devices and TNE. Full article
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