scholarly journals The Molecular Effects of Dietary Acid Load on Metabolic Disease (The Cellular PasaDoble: The Fast-Paced Dance of pH Regulation)

2021 ◽  
Vol 1 ◽  
Author(s):  
Morgan Williamson ◽  
Naima Moustaid-Moussa ◽  
Lauren Gollahon
Keyword(s):  
Metabolic Disease ◽  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Prolonged Exposure ◽  
The Body ◽  
Calcium Excretion ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Dietary Analysis ◽  
Wide Range

Metabolic diseases are becoming more common and more severe in populations adhering to western lifestyle. Since metabolic conditions are highly diet and lifestyle dependent, it is suggested that certain diets are the cause for a wide range of metabolic dysfunctions. Oxidative stress, excess calcium excretion, inflammation, and metabolic acidosis are common features in the origins of most metabolic disease. These primary manifestations of “metabolic syndrome” can lead to insulin resistance, diabetes, obesity, and hypertension. Further complications of the conditions involve kidney disease, cardiovascular disease, osteoporosis, and cancers. Dietary analysis shows that a modern “Western-style” diet may facilitate a disruption in pH homeostasis and drive disease progression through high consumption of exogenous acids. Because so many physiological and cellular functions rely on acid-base reactions and pH equilibrium, prolonged exposure of the body to more acids than can effectively be buffered, by chronic adherence to poor diet, may result in metabolic stress followed by disease. This review addresses relevant molecular pathways in mammalian cells discovered to be sensitive to acid - base equilibria, their cellular effects, and how they can cascade into an organism-level manifestation of Metabolic Syndromes. We will also discuss potential ways to help mitigate this digestive disruption of pH and metabolic homeostasis through dietary change.

Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation

2015 ◽  
Vol 129 (12) ◽  
pp. 1083-1096 ◽  
Author(s):  
Joseph B. McPhee ◽  
Jonathan D. Schertzer
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
The Body ◽  
Tissue Inflammation ◽  
Gut Barrier Function ◽  
Inflammatory Status ◽  
Obesity And Diabetes

The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain

2007 ◽  
Vol 293 (6) ◽  
pp. R2412-R2420 ◽  
Author(s):  
Li-Ming Chen ◽  
Inyeong Choi ◽  
Gabriel G. Haddad ◽  
Walter F. Boron
Keyword(s):  
Mouse Brain ◽  
Chronic Hypoxia ◽  
Ph Regulation ◽  
Protein Abundance ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Protein Levels ◽  
Stage Of Development ◽  
Wide Range ◽  
The Central Nervous System

In the mammalian CNS, hypoxia causes a wide range of physiological effects, and these effects often depend on the stage of development. Among the effects are alterations in pH homeostasis. Na+-coupled HCO3− transporters can play critical roles in intracellular pH regulation and several, such as NCBE and NBCn1, are expressed abundantly in the central nervous system. In the present study, we examined the effect of chronic continuous hypoxia on the expression of two electroneutral Na-coupled HCO3− transporters, SLC4a7 (NBCn1) and SLC4a10 (NCBE), in mouse brain, the first such study on any acid-base transporter. We placed the mice in normobaric chambers and either maintained normoxia (21% inspired O2) or imposed continuous chronic hypoxia (11% O2) for a duration of either 14 days or 28 days, starting from ages of either postnatal age 2 days (P2) or P90. We assessed protein abundance by Western blot analysis, loading equal amounts of total protein for each condition. In most cases, hypoxia reduced NBCn1 levels by 20–50%, and NCBE levels by 15–40% in cerebral cortex, subcortex, cerebellum, and hippocampus, both after 14 and 28 days, and in both pups and adults. We hypothesize that these decreases, which are out of proportion to the expected overall decreases in brain protein levels, may especially be important for reducing energy consumption.

scholarly journals Flavonoids on diabetic nephropathy: advances and therapeutic opportunities

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qichao Hu ◽  
Caiyan Qu ◽  
Xiaolin Xiao ◽  
Wenwen Zhang ◽  
Yinxiao Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Natural Products ◽  
Diabetic Nephropathy ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
The Body ◽  
Diabetic Patients ◽  
Public Attention ◽  
Wide Range ◽  
Tgf Β1

AbstractWith the advances in biomedical technologies, natural products have attracted substantial public attention in the area of drug discovery. Flavonoids are a class of active natural products with a wide range of pharmacological effects that are used for the treatment of several diseases, in particular chronic metabolic diseases. Diabetic nephropathy is a complication of diabetes with a particularly complicated pathological mechanism that affects at least 30% of diabetic patients and represents a great burden on public health. A large number of studies have shown that flavonoids can alleviate diabetic nephropathy. This review systematically summarizes the use of common flavonoids for the treatment of diabetic nephropathy. We found that flavonoids play a therapeutic role in diabetic nephropathy mainly by regulating oxidative stress and inflammation. Nrf-2/GSH, ROS production, HO-1, TGF-β1 and AGEs/RAGE are involved in the process of oxidative stress regulation. Quercetin, apigenin, baicalin, luteolin, hesperidin, genistein, proanthocyanidin and eriodictyol were found to be capable of alleviating oxidative stress related to the aforementioned factors. Regarding inflammatory responses, IL-1, IL-6β, TNF-α, SIRT1, NF-κB, and TGF-β1/smad are thought to be essential. Quercetin, kaempferol, myricetin, rutin, genistein, proanthocyanidin and eriodictyol were confirmed to influence the above targets. As a result, flavonoids promote podocyte autophagy and inhibit the overactivity of RAAS by suppressing the upstream oxidative stress and inflammatory pathways, ultimately alleviating DN. The above results indicate that flavonoids are promising drugs for the treatment of diabetic nephropathy. However, due to deficiencies in the effect of flavonoids on metabolic processes and their lack of structural stability in the body, further research is required to address these issues.

Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

2007 ◽  
Vol 293 (3) ◽  
pp. R1294-R1302 ◽  
Author(s):  
Amjad Kanaan ◽  
Robert M. Douglas ◽  
Seth L. Alper ◽  
Walter F. Boron ◽  
Gabriel G. Haddad
Keyword(s):  
Mammalian Cells ◽  
Adult Mouse ◽  
Brain Regions ◽  
Adult Brain ◽  
Mouse Heart ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Adult Mice ◽  
Sodium Hydrogen Exchanger ◽  
The Face

Several pulmonary and neurological conditions, both in the newborn and adult, result in hypercapnia. This leads to disturbances in normal pH homeostasis. Most mammalian cells maintain tight control of intracellular pH (pHi) using a group of transmembrane proteins that specialize in acid-base transport. These acid-base transporters are important in adjusting pHi during acidosis arising from hypoventilation. We hypothesized that exposure to chronic hypercapnia induces changes in the expression of acid-base transporters. Neonatal and adult CD-1 mice were exposed to either 8% or 12% CO2 for 2 wk. We used Western blot analysis of membrane protein fractions from heart, kidney, and various brain regions to study the response of specific acid-base transporters to CO2. Chronic CO2 increased the expression of the sodium hydrogen exchanger 1 (NHE1) and electroneutral sodium bicarbonate cotransporter (NBCn1) in the cerebral cortex, heart, and kidney of neonatal but not adult mice. CO2 increased the expression of electrogenic NBC (NBCe1) in the neonatal but not the adult mouse heart and kidney. Hypercapnia decreased the expression of anion exchanger 3 (AE3) in both the neonatal and adult brain but increased AE3 expression in the neonatal heart. We conclude that: 1) chronic hypercapnia increases the expression of the acid extruders NHE1, NBCe1 and NBCn1 and decreases the expression of the acid loader AE3, possibly improving the capacity of the cell to maintain pHi in the face of acidosis; and 2) the heterogeneous response of tissues to hypercapnia depends on the level of CO2 and development.

scholarly journals The effect of fenofibrate on expression of genes involved in fatty acids beta-oxidation and associated free-radical processes

2016 ◽  
Vol 62 (4) ◽  
pp. 426-430 ◽  
Author(s):  
A.P. Gureev ◽  
M.L. Shmatkova ◽  
V.Yu. Bashmakov ◽  
A.A. Starkov ◽  
V.N. Popov
Keyword(s):  
Fatty Acids ◽  
Free Radical ◽  
Metabolic Diseases ◽  
The Body ◽  
Antioxidant Systems ◽  
Peroxisome Proliferator ◽  
Ros Production ◽  
Free Radical Processes ◽  
Wide Range ◽  
Radical Processes

Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b-oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria. Enhancement of oxidative processes caused a 2-fold increase in the rate of reactive oxygen species (ROS) production, as evidenced by determination of the level of lipid peroxidation (LPO) products in the liver. Mitochondrial antioxidant systems are more sensitive to elevated ROS production, as they respond by increased expression of SOD2 and PRDX3 genes, than cytoplasmic and peroxisomal antioxidant systems, where expression of CAT1, SOD1, PRDX5 genes remained unaltered.

scholarly journals Effects of Methanolic Leaf Extract of Clinacanthus nutans on Fatty Acid Composition and Gene Expression in Male Obese Mice

2018 ◽  
Author(s):  
Samiaa Jamil Abdulwahid ◽  
Meng Yong Goh ◽  
Mahdi Ebrahimi ◽  
Norhafizah Mohtarrudin ◽  
Zailina Binti Hashim
Keyword(s):  
Fatty Acid ◽  
High Fat Diet ◽  
Leaf Extract ◽  
Metabolic Diseases ◽  
The Body ◽  
Health Concern ◽  
Obese Mice ◽  
High Fat ◽  
Wide Range ◽  
Clinacanthus Nutans

Obesity is a universal health concern that can lead to serious diseases. The side effects of synthetic anti-obesity drugs necessitate the finding of suitable natural/herbal alternatives. Mother nature offers a wide range of plants with medicinal properties that include crude extracts and isolated compounds which are effective for controlling and reducing weight gain. Obesity was induced in 60, 3-week-old male ICR mice, using high-fat diet (60% dietary energy from fat) for 16-week. The mice were divided at random into six groups with 10 mice: mice fed with high-fat diet (HFD) only, mice fed normal diet only (NC), and orlistat at 15.9 mg/kg (HFD+Orlistat), and mice in three other high-fat diet groups treated with methanolic leaf extract of Clinacanthus nutans (MECN) at 500, 1000 and 1500 mg/kg. After 21-day of the treatment, MECN significantly reduced (P<0.05) the body weight, visceral fat and muscle saturated fatty acid compositions. There was also significant downregulation of HSL, PPAR α and PPAR γ and SCD genes expressions in the obese mice treated with 1500 mg/kg MECN compared to the HFD group. Therefore, MECN is a potentially useful natural supplement for alleviating obesity and obesity-mediated metabolic diseases.

scholarly journals Metaflammation, NLRP3 Inflammasome Obesity and Metabolic Disease

2011 ◽  
Vol 3 (3) ◽  
pp. 168
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Nlrp3 Inflammasome ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
Metabolic Stress ◽  
Nutrient Sensing ◽  
Low Grade ◽  
Wide Range

BACKGROUND: Increasing prevalence of obesity gives rise to many problems associated with multiple morbidities, such as diabetes, hypertension, heart disease, sleep apnea and cancer. The mechanism of obesity is very complex, thus its link to various disease is poorly understood. This review highlights important concepts in our understanding of the pathogenesis of obesity and related complications.CONTENT: Many studies have tried to explore the exciting and puzzling links between metabolic homeostasis and inflammatory responses. A form of subclinical, low-grade systemic inflammation is known to be associated with both obesity and chronic disease. This, later called as "metaflammation", refers to metabolically triggered inflammation. The nutrient-sensing pathway and the immune response coordination are facilitated by these molecular sites in order to maintain homeostasis under diverse metabolic and immune conditions. Recent studies have found that the NLRP3 inflammasome during metabolic stress forms a tie linking TXNIP, oxidative stress, and IL-1β production. This provides new opportunities for research and therapy for the disease often described as the next global pandemic: type 2 diabetes mellitus (T2DM).SUMMARY: The crucial role of metaflammation in many complications of obesity shown by the unexpected overlap between inflammatory and metabolic sensors and their downstream tissue responses. Then great interest arose to explore the pathways that integrate nutrient and pathogen sensing, give more understanding in the mechanisms of insulin resistance type 2 diabetes, and other chronic metabolic pathologies. A family of intracellular sensors called NLR family is a critical component of the innate immune system. They can form multiprotein complexes, called inflammasome which is capable of responding to a wide range of stimuli including both microbial and self molecules by activating the cysteine protease caspase-1, leading to processing and secretion of the proinflammatory cytokines IL-1β and IL-18, which play crucial roles in host defense. Inflammasome dysregulation has been linked to some autoinflammatory and metabolic diseases. These provide opportunities to continue to improve our understanding of the nature of metaflammation in the hope of modifying it to prevent and treat diseasese.KEYWORDS: Inflammation, metaflammation, inflammasome, metabolic disease, obesity

scholarly journals Hyperinsulinemia: A Metabolic Disease, the Quality of Life of its Patients and Treatment

2020 ◽  
pp. 1-2
Author(s):  
Christos P Beretas ◽  
Keyword(s):  
Quality Of Life ◽  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Metabolic Diseases ◽  
The Body ◽  
Polycystic Ovaries ◽  
Metabolic Condition

Hyperinsulinemia is a metabolic condition that occurs mainly in people with increased body weight, which implies an increased body mass index (BMI) and the consequences it can have in long term. Many people suffer from hyperinsulinemia but do not know it, as they ignore their symptoms which are polycystic ovaries, hair loss, difficulty having children, sparse menstruation, etc. Hyperinsulinemia is a metabolic condition due to the fact that the body constantly produces an increased to excessive amount of insulin regardless of the amount of glucose present in the blood. Hyperinsulinemia should not be confused with and directly linked to diabetes, as type 2 diabetes may occur after several years of untreated hyperinsulinemia due to the natural fatigue of the pancreas due to its excessive and uninterrupted production of insulin. Usually people who show symptoms of hyperinsulinemia are predisposed as it can be diagnosed in newborns, it has arisen from other metabolic diseases such as isletoblastoma, liver disease, etc. It can also result from the administration of drugs such as contraceptives where after their cessation the body has returned to normal or unfortunately hyperinsulinemia may remain.

scholarly journals Fetal Programming of the Neuroendocrine-Immune System and Metabolic Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
R. E. Fisher ◽  
M. Steele ◽  
N. A. Karrow
Keyword(s):  
Metabolic Disease ◽  
Immune System ◽  
Metabolic Diseases ◽  
The Body ◽  
Intrauterine Environment ◽  
Maternal Malnutrition ◽  
Thrifty Phenotype ◽  
Thrifty Phenotype Hypothesis ◽  
Increased Risk ◽  
The Individual

Adverse uterine environments experienced during fetal development can alter the projected growth pattern of various organs and systems of the body, leaving the offspring at an increased risk of metabolic disease. The thrifty phenotype hypothesis has been demonstrated as an alteration to the growth trajectory to improve the survival and reproductive fitness of the individual. However, when the intrauterine environment does not match the extrauterine environment problems can arise. With the increase in metabolic diseases in both Westernized and developing countries, it is becoming apparent that there is an environmental disconnect with the extrauterine environment. Therefore, the focus of this paper will be to explore the effects of maternal malnutrition on the offspring’s susceptibility to metabolic disorders such as obesity, cardiovascular disease, and diabetes with emphasis on programming of the neuroendocrine-immune system.

scholarly journals Nicotinamide: Oversight of Metabolic Dysfunction through SIRT1, mTOR, and Clock Genes

2020 ◽  
Vol 17 ◽  
Author(s):  
Kenneth Maiese
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Serum Glucose ◽  
The Body ◽  
Trophic Factors ◽  
Metabolic Dysfunction ◽  
Innovative Strategy ◽  
Cellular Survival

Abstract:: Metabolic disorders that include diabetes mellitus present significant challenges for maintaining the welfare of the global population. Metabolic diseases impact all systems of the body and despite current therapies that offer some protection through tight serum glucose control, ultimately such treatments cannot block the progression of disability and death realized with metabolic disorders. As a result, novel therapeutic avenues are critical for further development to address these concerns. An innovative strategy involves the vitamin nicotinamide and the pathways associated with the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and clock genes. Nicotinamide maintains an intimate relationship with these pathways to oversee metabolic disease and improve glucose utilization, limit mitochondrial dysfunction, block oxidative stress, potentially function as antiviral therapy, and foster cellular survival through mechanisms involving autophagy. However, the pathways of nicotinamide, SIRT1, mTOR, AMPK, and clock genes are complex and involve feedback pathways as well as trophic factors such as erythropoietin that require a careful balance to ensure metabolic homeostasis. Future work is warranted to gain additional insight into these vital pathways that can oversee both normal metabolic physiology and metabolic disease.

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