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Topic Review
Cardio- and Neurometabolic Adipobiology
Abstract: Studies over the past 30 years have revealed that adipose tissue is the major endocrine and paracrine organ of the human body. Arguably, adiopobiology has taken its reasonable place in studying obesity and related cardiometabolic diseases (CMDs), including Alzheimer’s disease (AD), which is viewed herein as a neurometabolic disorder. The pathogenesis and therapy of these diseases are multiplex at basic, clinical and translational levels. Our present goal is to describe new developments in cardiometabolic and neurometabolic adipobiology. Accordingly, we focus on adipose- and/or skeletal muscle-derived signaling proteins (adipsin, adiponectin, nerve growth factor, brain-derived neuroptrophic factor, neurotrophin-3, irisin, sirtuins, Klotho, neprilysin, follistatin-like protein-1, meteorin-like (metrnl), as well as growth differentiation factor 11) as examples of metabotrophic factors (MTFs) implicated in the pathogenesis and therapy of obesity and related CMDs. We argue that these pathologies are MTF-deficient diseases. In 1993 the “vascular hypothesis of AD” was published and in the present review we propose the “vasculometabolic hypothesis of AD.” We discuss how MTFs could bridge CMDs and neurodegenerative diseases, such as AD. Greater insights on how to manage the MTF network would provide benefits to the quality of human life.
  • 1.2K
  • 25 Apr 2021
Topic Review
Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases
The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of pathological molecules and microorganisms. Bile acids are small molecules synthesized from cholesterol in the liver, secreted into the duodenum, and transformed to secondary or tertiary bile acids by the gut microbiota. Bile acids interact with bile acid receptors (BARs) or gut microbiota, which plays a key role in maintaining the homeostasis of the intestinal barrier.
  • 1.2K
  • 25 Aug 2023
Topic Review
Obesity-related Insulin Resistance
Obesity-related IR implicates the PI3-K pathway that confers the metabolic effects of insulin. Numerous and complex pathogenic pathways link obesity with the development of IR, including chronic inflammation, mitochondrial dysfunction (with the associated production of reactive oxygen species and endoplasmic reticulum stress), gut microbiota dysbiosis and adipose extracellular matrix remodelling.
  • 1.2K
  • 23 Feb 2021
Topic Review
Neuropeptide Y in Energy Balance Regulation
Energy balance is regulated by several hormones and peptides, and neuropeptide Y is one of the most crucial in feeding and energy expenditure control. The neuropeptide Y (NPY), is a potent orexigenic peptide pointed out as an obesogenic factor. NPY is regulated by a series of peripheral nervous and humoral signals that are responsive to nutrient sensing, but its role in the energy balance is also intricately related to the energetic status, namely mitochondrial function.
  • 1.2K
  • 25 Apr 2023
Topic Review
Wnt Signaling to Vascular Complications in T2DM
Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents “mandatory damage” in the development of microvascular complications and only “introductory damage” in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. 
  • 1.2K
  • 04 Jul 2022
Topic Review
A-FABP in Metabolic Diseases
Adipocyte fatty acid-binding protein (A-FABP), which is also known as ap2 or FABP4, is a fatty acid chaperone that has been further defined as a fat-derived hormone. It regulates lipid homeostasis and is a key mediator of inflammation. Circulating levels of A-FABP are closely associated with metabolic syndrome and cardiometabolic diseases with imminent diagnostic and prognostic significance. Numerous animal studies have elucidated the potential underlying mechanisms involving A-FABP in these diseases. Recent studies demonstrated its physiological role in the regulation of adaptive thermogenesis and its pathological roles in ischemic stroke and liver fibrosis. Due to its implication in various diseases, A-FABP has become a promising target for the development of small molecule inhibitors and neutralizing antibodies for disease treatment. This review summarizes the clinical and animal findings of A-FABP in the pathogenesis of cardio-metabolic diseases in recent years.
  • 1.2K
  • 22 Sep 2021
Topic Review
Resveratrol in Ovarian Cancer
Resveratrol, a natural polyphenolic stilbenoid, is a phytoestrogen. Most notably, accumulative evidence supports the notion that resveratrol has immunomodulatory and anticancer properties, and its antioxidant activity and ability to inhibit enzymes may contribute to its anti-inflammatory properties.
  • 1.2K
  • 12 Nov 2021
Topic Review
Complete Androgen Insensitivity Syndrome
Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes.
  • 1.2K
  • 18 Sep 2021
Topic Review
Branched-Chain Amino Acids and Insulin Resistance
There has been a wide debate about the branched-chain amino acids (BCAA) leucine, valine, and isoleucine, with, on the one hand, the supporters of their anabolic effects and, on the other hand, those who suspect them of promoting insulin resistance. Indeed, the role of leucine in the postprandial activation of protein synthesis has been clearly established, even though supplementation studies aimed at taking advantage of this property are rather disappointing. Furthermore, there is ample evidence of an association between the elevation of their plasma concentrations and insulin resistance or the risk of developing type 2 diabetes, although there are many confounding factors, starting with the level of animal protein consumption. 
  • 1.2K
  • 06 Jan 2023
Topic Review
Insulin-Degrading Enzyme in Insulin Clearance
Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50–80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn2+-metalloprotease that degrades insulin and several other intermediate-size peptides. Both insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts towards developing IDE inhibitors as therapeutics in diabetic patients have attracted attention during the last decades.
  • 1.2K
  • 23 Mar 2021
Topic Review
Sodium Glucose Co-Transporter 2 Inhibitor
Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i–HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.
  • 1.2K
  • 03 Nov 2020
Topic Review
PASK and Liver Antioxidants
PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. It is a nutrient sensor and during fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis.
  • 1.2K
  • 24 Jan 2022
Topic Review
Metformin in Pregnancy
Metformin is a first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Although metformin demonstrates beneficial and protective cardiovascular effects for the mother, evidence suggests metformin may not be favourable for the short and long-term metabolic health of the offspring. Metformin can cross the placenta and could have a role in fetal programming.
  • 1.2K
  • 07 Jun 2021
Topic Review
Metabolic Syndrome Prevention
The prevalence of metabolic syndrome (MetS) is presently an alarming public health problem globally. Oxidative stress has been postulated to be strongly correlated with MetS, such as obesity, type 2 diabetes, hypertension, cardiovascular diseases, and certain cancers. In addition, substantial evidence of the role of antioxidants in human health and chronic disease prevention exist. Cereals are important staple foods which account for a huge proportion of the human diet. However, owing to recent growing demand and the search for natural antioxidants, the development of cereal peptidic antioxidants using bioinformatics approaches, simultaneous application of green food processing technologies with enzymatic and fermentation methods could potentially be used as health-promoting functional ingredients, foods or dietary supplements for the prevention and management of MetS. However, the obtainability and achievability of human equivalent doses under physiological conditions still remains controversial and requires further studies.
  • 1.2K
  • 02 Apr 2021
Topic Review
Mitophagy Regulates Neurodegenerative Diseases
Mitochondria are the primary source of cellular energy regulating cellular metabolism and physiology. To maintain cellular metabolism and homeostasis, damaged or unwanted mitochondria should be eliminated through mitophagy, a form of mitochondrial quality control process. Mitophagy is a highly selective autophagy process that eliminates dysfunctional or redundant mitochondria through multiple regulatory pathways in a ubiquitin-dependent or -independent manner. Since the term “mitophagy” was first coined by Dr. Lemasters in 2005, accumulating scientific evidence reveals that the accumulation of damaged mitochondria is one of the causal factors for various human diseases including neurodegenerative and cardiovascular diseases as well as cancers. Among all the cell types affected by mitochondrial dysfunction, neurons are vulnerable to mitochondrial damage due to their high energy demand. 
  • 1.2K
  • 11 Aug 2021
Topic Review
Citrate Pathophysiology and Bone Diseases
Citrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. 
  • 1.2K
  • 19 Sep 2022
Topic Review
Hepatocrinology
Hepatocrinology is defined as the bidirectional, complex relationship between hepatic and endocrine physiology and dysfunctions. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes.
  • 1.2K
  • 24 Jul 2021
Topic Review
Gut Microbiome Vehicle Targeted Drug Delivery
The incidence of colon-associated diseases in the west has risen dramatically over the past several decades, as evidenced by conditions such as Crohn’s disease, irritable bowel syndrome, colorectal cancer, and ulcerative colitis.
  • 1.2K
  • 31 Dec 2021
Topic Review
Long-Term Effects of Bariatric Surgery on Gut Microbiota
Obesity is a worldwide disease characterized by an excessive body fat accumulation and by the presence of a subclinical  chronic inflammatory status, which is associated with high morbidity and mortality rates. There are multiple pharmacological and non-pharmacological (exercise or dietary interventions) therapeutic strategies to face this disease. However, when these therapies failed, bariatric surgery is the most efficient treatment for obesity. In the last few years, different research studies have demonstrated a key role of gut microbiota, defined as all the microorganisms that habit in the digestive tract, in the development and progression of obesity. For that reason, going deepen in the knowledge of the link between bariatric surgery and gut microbiota could elucidate mechanistic and therapeutic approaches.
  • 1.2K
  • 23 Nov 2021
Topic Review
Metabolic Engineering for FA Production
Metabolic engineering is a cutting-edge field that aims to produce simple, readily available, and inexpensive biomolecules by applying different genetic engineering and molecular biology techniques. Fatty acids (FAs) play an important role in determining the physicochemical properties of membrane lipids and are precursors of biofuels. Microbial production of FAs and FA-derived biofuels has several advantages in terms of sustainability and cost. Conventional yeast Saccharomyces cerevisiae is one of the models used for FA synthesis. Several genetic manipulations have been performed to enhance the citrate accumulation and its conversation into acetyl-CoA, a precursor for FA synthesis. Success has been achieved in producing different chemicals, including FAs and their derivatives, through metabolic engineering.
  • 1.2K
  • 04 Aug 2021
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