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Topic Review
Preclinical and Clinical Endeavors Targeting Mitochondria
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target.
  • 972
  • 26 Feb 2024
Topic Review
Effects of Excess Maternal Fructose Intake
Fructose is a 6-carbon polyhydroxy ketone monosaccharide that shares the same chemical formula and is an isomer of glucose. Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit.
  • 968
  • 01 Nov 2022
Topic Review
Endocrine-Disrupting Chemicals and Female Puberty
In recent decades pubertal onset in girls is considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, several reports suggesting that EDCs may have a role in the secular trend in pubertal maturation, at least in girls. However, relevant studies give inconsistent results. On the other hand, the majority of girls with idiopathic precocious or early puberty present the growth pattern of constitutional advancement of growth (CAG), i.e., growth acceleration soon after birth. CAG is unrelated to exposure to EDCs and is the major determinant of precocious or early puberty. EDCs, at most, have a minor effect on the timing of pubertal onset in girls.
  • 966
  • 30 Jun 2021
Topic Review
Dietary Intake and Energy Expenditure in Breast Cancer
Many breast cancer survivors (BCS) gain fat mass and lose fat-free mass during treatment (chemotherapy, radiation, surgery) and estrogen suppression therapy, which increases the risk of developing comorbidities. Whether these body composition alterations are a result of changes in dietary intake, energy expenditure, or both is unclear. Thus, we reviewed studies that have measured components of energy balance in BCS who have completed treatment. Longitudinal studies suggest that BCS reduce self-reported energy intake and increase fruit and vegetable consumption. Although some evidence suggests that resting metabolic rate is higher in BCS than in age-matched controls, no study has measured total daily energy expenditure (TDEE) in this population. Whether physical activity levels are altered in BCS is unclear, but evidence suggests that light-intensity physical activity is lower in BCS compared to age-matched controls. We also discuss the mechanisms through which estrogen suppression may impact energy balance and develop a theoretical framework of dietary intake and TDEE interactions in BCS. Preclinical and human experimental studies indicate that estrogen suppression likely elicits increased energy intake and decreased TDEE, although this has not been systematically investigated in BCS specifically. Estrogen suppression may modulate energy balance via alterations in appetite, fat-free mass, resting metabolic rate, and physical activity. There are several potential areas for future mechanistic energetic research in BCS (e.g., characterizing predictors of intervention response, appetite, dynamic changes in energy balance, and differences in cancer sub-types) that would ultimately support the development of more targeted and personalized behavioral interventions. 
  • 965
  • 11 Oct 2021
Topic Review
Aging and Muscle Oxygen Utilization
The cardiovascular and skeletal muscle systems are intrinsically interconnected, sharing the goal of delivering oxygen to metabolically active tissue. Deficiencies within those systems that affect oxygen delivery to working tissues are a hallmark of advancing age. Oxygen delivery and utilization are reflected as muscle oxygen saturation (SmO2) and are assessed using near-infrared resonance spectroscopy (NIRS). SmO2 has been observed to be reduced by ~38% at rest, ~24% during submaximal exercise, and ~59% during maximal exercise with aging (>65 y).
  • 962
  • 19 Oct 2022
Topic Review
Manganese Exposure and Metabolic Syndrome
Manganese (Mn) is an essential element acting as a co-factor of superoxide dismutase, and it is potentially beneficial for cardiometabolic health by reducing oxidative stress. Metabolic syndrome (MetS) is defined as a cluster of metabolic alterations that contributes to a higher risk of cardiovascular disease (CVD), type 2 diabetes (T2D), and all-cause mortality. Association between Mn exposure from diet and environment, and the risk of MetS are described here.
  • 947
  • 19 Apr 2022
Topic Review
miRNA and lncRNA Dysregulation in Diabetes
Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the ‘symptom complex’ in diabetes.
  • 946
  • 02 Nov 2022
Topic Review
Thyroid Gland Homeostasis and TGF-β
Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases.
  • 941
  • 06 Sep 2021
Topic Review
Pharmaceutical Drug and Metabolic Adaptions/Reprogramming in β-Cells
Islet inflammation in T1DM is characterized by leukocyte infiltrates, in particular macrophages and T-cells which damage β-cells by release of cytokines, ROS and NO and also activation of death-receptor-mediated death pathways and subsequent phagocytosis. Production of cytokines such as INF-γ, TNFα and IL-1β act in synergy to promote elevation in concentration and increase in activity of NADPH oxidase and iNOS consequently increasing the formation of products including ROS and NO, respectively. The mechanism of action of INF-γ, TNFα and IL-1β involves stimulation of transcription factors including NFκB (in mouse islet β-cells).
  • 941
  • 29 Mar 2022
Topic Review
Mitochondrial Ca2+ and Tumor Cell
Mitochondrial Ca2+ transport-related processes are involved in important biological processes of tumor cells including proliferation, metabolism, and apoptosis. In particular, MCU and its regulatory proteins represent a new era in the study of MCU-mediated mitochondrial Ca2+ homeostasis in tumors. 
  • 941
  • 30 Jun 2022
Topic Review
Immune Cell Type-Specific Metabolic Reprogramming
Immunometabolism is an emerging discipline in cancer immunotherapy. Tumor tissues are heterogeneous and influenced by metabolic reprogramming of the tumor immune microenvironment (TIME). In the TIME, multiple cell types interact, and the tumor and immune cells compete for limited nutrients, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of individual cell types may influence the outcomes of immunotherapy. Understanding the metabolic competition for access to limited nutrients between tumor cells and immune cells could reveal the breadth and complexity of the TIME and aid in developing novel therapeutic approaches for cancer.
  • 940
  • 18 Mar 2022
Topic Review
Metabolic Mechanisms in Obesity-Related Childhood Asthma
Obesity-related asthma is a heterogeneous childhood asthma phenotype with rising prevalence. Observational studies identify early-life obesity or weight gain as risk factors for childhood asthma development.  Oxidative stress is a central pathogenetic process in obesity-related childhood asthma and is considered to drive other metabolic processes, including dysregulation of fatty acids, peripheral blood ketones, amino acid metabolism, and insulin resistance.
  • 936
  • 08 Mar 2023
Topic Review
Kidney Disease in Diabetic Patients
Diabetic patients often present diabetic kidney disease (DKD), a burdensome complication that can be silent for years. The average time of onset of kidney impairment in diabetic patients is about 7–10 years. The clinical impact of DKD is dangerous not only for the risk of progression to end-stage renal disease and therefore to renal replacement therapies, but also because of the associated increase in cardiovascular events.
  • 935
  • 09 Jul 2021
Topic Review
Human Milk Metabolic Hormones
Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These essential hormones might play an important role in the regulation of metabolic reprogramming of the new-born infant. The protective activity of HM is thought to be due to the presence of bioactive molecules that are dynamic in response to maternal conditions and can positively modulate energy metabolism and inflammatory responses in infants and mothers. Hormones such as leptin, adiponectin, ghrelin, insulin, resistin, obestatin and apelin have been recently identified in HM.
  • 935
  • 24 Sep 2021
Topic Review
Vitamin D in the Context of Evolution
For at least 1.2 billion years, eukaryotes have been able to synthesize sterols and, therefore, can produce vitamin D when exposed to UV-B. Vitamin D endocrinology was established some 550 million years ago in animals, when the high-affinity nuclear receptor VDR (vitamin D receptor), transport proteins and enzymes for vitamin D metabolism evolved. This enabled vitamin D to regulate, via its target genes, physiological process, the first of which were detoxification and energy metabolism. In this way, vitamin D was enabled to modulate the energy-consuming processes of the innate immune system in its fight against microbes. In the evolving adaptive immune system, vitamin D started to act as a negative regulator of growth, which prevents overboarding reactions of T cells in the context of autoimmune diseases. When, some 400 million years ago, species left the ocean and were exposed to gravitation, vitamin D endocrinology took over the additional role as a major regulator of calcium homeostasis, being important for a stable skeleton.
  • 934
  • 29 Jul 2022
Topic Review
The Role Vitamin D Reducing Risk Inflammatory Disease
Numerous pleiotropic effects have been reported for vitamin D (vit D) since its discovery a century ago. Today it is well known that in addition to its pivotal role in calcium homeostasis and bone metabolism, vit D has antibacterial, anti-proliferative, immunomodulatory, and anti-inflammatory actions, among other beneficial properties. In the context of inflammatory-based diseases, vit D and its receptor VDR might fulfil their roles as gene regulators through direct gene regulation and epigenetic mechanisms.
  • 929
  • 01 Mar 2023
Topic Review
Mechanism of Metabolic Syndrome Formation
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that can predispose an individual to a greater risk of developing type-2 diabetes and cardiovascular diseases. The cluster includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia, all of which are risk factors to public health. While searching for a link among the aforementioned malaises, clues have been focused on the cell membrane domain caveolae, wherein the MetS-associated active molecules are co-localized and interacted with to carry out designated biological activities. Caveolae disarray could induce all of those individual metabolic abnormalities to be present in animal models and humans, providing a new target for therapeutic strategy in the management of MetS. Using a cellular model of caveolae inter-cellular movement (with the eGFP-labelledcaveolae), several potential herbal extracts and nutrients have shown their effects on externalization of caveolae, opening an initiative for the associated metabolic pathways. This also is supported by recent publications which have demonstrated that some clinical effective Chinese herbal or herbal extracts for the treatments of hypertension, hyperlipidemia, and hyperglycemia can have a stimulating effect on cellular caveolae bioactivity. A new therapeutic target to effectively treat and prevent metabolic syndrome safely without significant side effects may become possible.
  • 920
  • 28 Sep 2021
Topic Review
Trans-Endothelial Fatty Acid Transport and Cardiac Metabolism/Contractile
The heart is a metabolic omnivore that combusts a considerable amount of energy substrates, mainly long-chain fatty acids (FAs) and others such as glucose, lactate, ketone bodies, and amino acids. There is emerging evidence that muscle-type continuous capillaries comprise the rate-limiting barrier that regulates FA uptake into cardiomyocytes. The transport of FAs across the capillary endothelium is composed of three major steps—the lipolysis of triglyceride on the luminal side of the endothelium, FA uptake by the plasma membrane, and intracellular FA transport by cytosolic proteins. In the heart, impaired trans-endothelial FA (TEFA) transport causes reduced FA uptake, with a compensatory increase in glucose use. In most cases, mice with reduced FA uptake exhibit preserved cardiac function under unstressed conditions. When the workload is increased, however, the total energy supply relative to its demand (estimated with pool size in the tricarboxylic acid (TCA) cycle) is significantly diminished, resulting in contractile dysfunction. The supplementation of alternative fuels, such as medium-chain FAs and ketone bodies, at least partially restores contractile dysfunction, indicating that energy insufficiency due to reduced FA supply is the predominant cause of cardiac dysfunction. 
  • 919
  • 20 Jan 2022
Topic Review
Mobile Tools to Manage Diabetes
Assessment tools on mobile platforms have the ability to capture multiple aspects of dietary behavior in real-time throughout the day to inform and improve diabetes management and insulin dosing. Dietary intake and behaviors are essential components of diabetes management. 
  • 917
  • 30 Apr 2021
Topic Review
Dietary Sulfur Amino Acid Restriction
Dietary sulfur amino acid restriction, also referred to as methionine restriction, increases food intake and energy expenditure and alters body composition in rodents, resulting in improved metabolic health and a longer lifespan. Among the known nutrient-responsive signaling pathways, the evolutionary conserved integrated stress response (ISR) is a lesser-understood candidate in mediating the hormetic effects of dietary sulfur amino acid restriction (SAAR). 
  • 915
  • 18 Aug 2022
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