scholarly journals Metabolic Effects of pH Enhanced Ground Beef in Diet-induced Obese Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1234-1234
Author(s):  
Kalhara Menikdiwela ◽  
Anna DesHotels ◽  
Kembra Albracht-Schulte ◽  
Shane Scoggin ◽  
Lauren Gollahon ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Mrna Level ◽  
Ground Beef ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
P Value ◽  
Low Grade ◽  
Fat Cell ◽  
Final Body Weight ◽  
Glucose Clearance

Abstract Objectives Western diets, characterized by higher amounts of saturated fats, fatty proteins, and lower consumption of fruits, vegetables and lean proteins (alkaline diet) has been suggested to contribute to metabolic diseases (e.g., obesity), through low-grade metabolic acidosis (low pH). Hence, our objective was to test the effects of diets rich in beef prepared at various pH levels, in diet induced obese B6 mice. We hypothesized that metabolic health will be improved by consuming a diet containing pH-enhanced cooked ground beef, compared to a non pH-enhanced beef diet. Methods B6 male and female mice were randomized (n = 5) into 6 groups; low fat (LF), pH-enhanced (ammonia) LF (LFN), high fat (HF), pH-enhanced HF (HFN), HF with beef (HFB), pH-enhanced HF beef (HFBN). Weight gain and food intake were measured weekly (for 12 weeks) and a glucose tolerance test (GTT) was performed at week 10. Tissues, including white adipose tissue (WAT) and liver were collected and used for histology, RNA and protein isolation, followed by analyses of gene (qRT-PCR) and proteins (Western blotting) related to fat and glucose metabolism. Results Final body weight was significantly higher in HF group compared to LF and LFN groups in males, but not in females. Moreover, glucose clearance was significantly better in LF groups compared to HF group for both male and females. Interestingly, pH enhanced groups (HFN and HFBN) demonstrated significantly improved glucose clearance at the end of GTT compared to HF group only in males. Male WAT had smaller fat cell size, and greater fat cell number (P < 0.05) in HFN and HFBN compared to HF and HFB respectively. HFBN showed less hepatic fat accumulation in male mice compared to HFB group. Corroborating these, mRNA level of fatty acid oxidation marker Cpt1α was upregulated in HFBN group compared to HFB (P value 0.07) in male liver. Conclusions Findings from this HF diet-induced obesity research suggest that there are potential metabolic benefits of increased dietary pH, through improved glucose clearance and fat metabolism. However, additional research is warranted to determine the underlying mechanisms and whether similar effects will be observed with LF pH-enhanced beef diets. These results can be further translated to human subjects to understand interactions between beef, pH and fat content on metabolic diseases. Funding Sources Empirical Foods, Inc.

IL-6 signalling in exercise and disease

2007 ◽  
Vol 35 (5) ◽  
pp. 1295-1297 ◽  
Author(s):  
B.K. Pedersen
Keyword(s):  
Type 2 Diabetes ◽  
Dominant Negative ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Low Grade ◽  
Healthy Humans ◽  
Multinucleated Cells ◽  
Anti Inflammatory

Low-grade chronic inflammation is a feature of Type 2 diabetes and appears to play a pathogenetic role in insulin resistance. It is well known that cytokines, besides their immunoregulatory roles, are important players in metabolism. Moreover, it has become evident that skeletal muscles express several cytokines, which belong to distinct cytokine classes. IL-6 (interleukin-6) is a pleiotropic cytokine produced by virtually all multinucleated cells including skeletal myocytes where it is produced in response to contraction. IL-6 is subsequently released into the circulation, where it works in a hormone-like fashion to induce lipolysis and fat oxidation. In more recent experiments, it has been shown that IL-6 infusion increases glucose disposal during a hyperinsulinaemic euglycaemic clamp in healthy humans. IL-6 treatment of myotubes increases fatty acid oxidation, basal and insulin-stimulated glucose uptake and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increases AMPK (AMP-activated protein kinase) and the metabolic effects of IL-6 were abrogated in AMPK dominant negative-infected cells. Finally, IL-6 mediates anti-inflammatory effects by stimulating the production of anti-inflammatory cytokines and by suppressing TNFα (tumour necrosis factor α) production. We suggest that IL-6 and other muscle-derived cytokines (myokines) may play a role in defending Type 2 diabetes.

The Inflammation Network in the Pathogenesis of Erectile Dysfunction: Attractive Potential Therapeutic Targets

2020 ◽  
Vol 26 (32) ◽  
pp. 3955-3972
Author(s):  
Ecem Kaya-Sezginer ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Metabolic Diseases ◽  
Inflammatory Marker ◽  
Attractive Potential ◽  
Common Denominator ◽  
Low Grade ◽  
Antiinflammatory Drugs ◽  
Male Population ◽  
Low Grade Inflammation

Background: Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, and diabetes. Objective: This review will present an overview of preclinical and clinical data regarding common inflammatory mechanisms involved in the pathogenesis of ED associated with metabolic diseases and the effect of antiinflammatory drugs on ED. Methods: A literature search of existing pre-clinical and clinical studies was performed on databases [Pubmed (MEDLINE), Scopus, and Embase] from January 2000 to October 2019. Results: Low-grade inflammation is a possible pathological role in endothelial dysfunction as a consequence of ED and other related metabolic diseases. Increased inflammation and endothelial/prothrombotic markers can be associated with the presence and degree of ED. Pharmacological therapy and modification of lifestyle and risk factors may have a significant role in the recovery of erectile response through reduction of inflammatory marker levels. Conclusion: Inflammation is the least common denominator in the pathology of ED and metabolic disorders. The inflammatory process of ED includes a shift in the complex interactions of cytokines, chemokines, and adhesion molecules. These data have established that anti-inflammatory agents could be used as a therapeutic opportunity in the prevention and treatment of ED. Further research on inflammation-related mechanisms underlying ED and the effect of therapeutic strategies aimed at reducing inflammation is required for a better understanding of the pathogenesis and successful management of ED.

Periodontal Pathogens and Neuropsychiatric Health

2020 ◽  
Vol 20 (15) ◽  
pp. 1353-1397 ◽  
Author(s):  
Abhishek Wadhawan ◽  
Mark A. Reynolds ◽  
Hina Makkar ◽  
Alison J. Scott ◽  
Eileen Potocki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Periodontal Pathogens ◽  
Synergistic Interactions ◽  
Brain Vasculature ◽  
Micro Rnas ◽  
Clinical Conditions ◽  
Low Grade Inflammation ◽  
Neuropsychiatric Illness

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

scholarly journals Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos
Keyword(s):  
Immune System ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Nuclear Factor Κb ◽  
Low Grade ◽  
Beneficial Effects ◽  
Health And Disease ◽  
Immunological Reactions ◽  
And Function ◽  
Positive Properties

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

scholarly journals Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1

2021 ◽  
Vol 22 (15) ◽  
pp. 7988
Author(s):  
Andrea Coppola ◽  
Barbara Capuani ◽  
Francesca Pacifici ◽  
Donatella Pastore ◽  
Roberto Arriga ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Interleukin 2 ◽  
High Mobility ◽  
High Mobility Group ◽  
Low Grade ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Activation of innate immunity and low-grade inflammation contributes to hyperglycemia and an onset of Type 2 Diabetes Mellitus (T2DM). Interleukin-2 (IL-2), leptin, High Mobility Group Box-1 (HMGB-1), and increased glucose concentrations are mediators of these processes also by modulating peripheral blood mononuclear cells (PBMCs) response. The aim of this study was to investigate if HMGB-1 and IL-2 turn on PBMCs and their leptin secretion. In isolated human PBMCs and their subpopulations from healthy individuals and naïve T2DM patients, leptin release, pro-inflammatory response and Toll-like Receptors (TLRs) activation was measured. After treatment with IL-2 and HMGB1, NK (Natural Killer) have the highest amount of leptin secretion, whilst NK-T have the maximal release in basal conditions. TLR4 (TAK242) and/or TLR2 (TLR2-IgA) inhibitors decreased leptin secretion after IL-2 and HMGB1 treatment. A further non-significant increase in leptin secretion was reported in PBMCs of naive T2DM patients in response to IL-2 and HMGB-1 stimulation. Finally, hyperglycemia or hyperinsulinemia might stimulate leptin secretion from PBMCs. The amount of leptin released from PBMCs after the different treatments was enough to stimulate the secretion of IL-1β from monocytes. Targeting leptin sera levels and secretion from PBMCs could represent a new therapeutic strategy to counteract metabolic diseases such as T2DM.

INHERITED METABOLIC DISORDERS AND HEART DISEASES

2019 ◽  
Author(s):  
Vjekoslav Krželj ◽  
Ivana Čulo Čagalj
Keyword(s):  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Technological Development ◽  
Heart Diseases ◽  
Glycogen Storage ◽  
Acid Oxidation ◽  
Lysosomal Storage ◽  
Glycogen Storage Diseases ◽  
Coronary Diseases ◽  
Inherited Metabolic Disorders

Inherited metabolic disorders can cause heart diseases, cardiomyopathy in particular, as well as cardiac arrhythmias, valvular and coronary diseases. More than 40 different inherited metabolic disorders can provoke cardiomyopathy, including lysosomal storage disorders, fatty acid oxidation defects, organic acidemias, amino acidopathies, glycogen storage diseases, congenital disorders of glycosylation as well as peroxisomal and mitochondrial disorders. If identified and diagnosed on time, some of congenital metabolic diseases could be successfully treated. It is important to assume them in cases when heart diseases are etiologically undefined. Rapid technological development has made it easier to establish the diagnosis of these diseases. This article will focus on common inherited metabolic disorders that cause heart diseases, as well as on diseases that might be possible to treat.

SGLT2 inhibitors as calorie restriction-mimetics: insights on longevity pathways and age-related diseases

Endocrinology ◽  
2021 ◽  
Author(s):  
Caroline W S Hoong ◽  
Marvin W J Chua
Keyword(s):  
Calorie Restriction ◽  
Stress Resistance ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Vascular Inflammation ◽  
Sglt2 Inhibitors ◽  
Acid Oxidation ◽  
The Metabolic Syndrome ◽  
Age Related ◽  
Energy Deprivation

Abstract SGLT2 inhibitors induce glycosuria, reduce insulin levels, promote fatty acid oxidation and ketogenesis. By promoting a nutrient deprivation state, SGLT2 inhibitors upregulate the energy deprivation sensors AMPK and SIRT1, inhibit the nutrient sensors mTOR and insulin/IGF-1, and modulate the closely-linked HIF-2α/HIF-1α pathways. Phosphorylation of AMPK and upregulation of adiponectin and PPAR-α favour a reversal of the metabolic syndrome which have been linked to suppression of chronic inflammation. Downregulation of insulin/IGF1 pathways and mTOR signalling from a reduction in glucose and circulating amino acids promote cellular repair mechanisms including autophagy and proteostasis which confer cellular stress resistance and attenuate cellular senescence. SIRT1, another energy sensor activated by NAD+ in nutrient-deficient states, is reciprocally activated by AMPK, and can deacetylate and activate transcription factors such as PCG-1α, TFAM and NRF2 that regulate mitochondrial biogenesis. FOXO3 transcription factor which target genes in stress resistance, is also activated by AMPK and SIRT1. Modulation of these pathways by SGLT2 inhibitors have been shown to alleviate metabolic diseases, attenuate vascular inflammation and arterial stiffness, improve mitochondrial function and reduce oxidative stress-induced tissue damage. Compared to other calorie restriction mimetics such as metformin, rapamycin, resveratrol and NAD+ precursors, SGLT2 inhibitors appear to be the most promising in the treatment of ageing-related diseases, due to its regulation of multiple longevity pathways that closely resemble that achieved by calorie restriction, and their established efficacy in reduction in cardiovascular events and all-cause mortality. Evidence is compelling for the role of SGLT2 inhibitors as a calorie restriction mimetic in anti-ageing therapeutics.

Role of susceptibility weighted imaging (SWI) in assessment of intra axial brain neoplasms in adults

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Pasant Mohamed Abo-Elhoda Darwish Mohamed Abo-Elhoda ◽  
Hesham Mahmoud Ahmed Mansour ◽  
Yosra Abdelzaher Abdullah ◽  
Eman Ahmed Fouad Darwish
Keyword(s):  
Brain Neoplasms ◽  
Tumor Size ◽  
Venous Blood ◽  
Brain Parenchyma ◽  
P Value ◽  
Susceptibility Weighted Imaging ◽  
Low Grade ◽  
Chi Square ◽  
Cross Sectional

Abstract Background Susceptibility weighted imaging (SWI) is a 3D gradient-echo MR technique that is based on blood oxygen level dependent (BOLD) induced phase effects between the venous blood and the surrounding brain parenchyma. SW-MR imaging allows for noninvasive visualization of small veins at submillimeter resolution and, therefore, is used to depict venous architecture in brain lesions. The extreme sensitivity of SWI for the detection of neovascularity (venous blood), haemorrhage, and calcification has been an indispensable tool for characterization of the internal architecture of brain tumours. Objectives Is to evaluate the role of Susceptibility weighted imaging in assessment of adults Intra axial brain Neoplasms, and its ability to characterize them into high and low grade lesions in comparison to histopathology which will be used as gold standard. Methods A cross sectional study including 31 patients suspecting intracranial brain neoplasm radiologically and clinically, conducted at Private center, the patients were investigated using Siemens machine Magnetom Skyra 3T, the period was between January 2018 till the end of June 2019 . Results Our study included 31 patients. Including 15 female and 16 male patients, with the patient’s age ranging from 20 to 68 years old with median 48 years old ranging from 35.75 (25% percentile) to 58.75 (75% percentile). Among total cases, there were 8 patients with grade 2 glioma, 10 patients with grade 3 glioma and 6 patients with grade 4 glioma, 2 patients with lymphoma and 5 patients with brain metastasis (1 lung cancer and 4 breast cancer). All the patients were evaluated with MRI including SWI sequence with special comment on the number of the intratumoral susceptibility signal (ITSS), the size of the ITSS, its morphology as well as the ratio of the ITSS to the tumor size, which were then correlated with the patient histopathological results obtained later. The study revealed that the best parameter to accurately grade the tumor is the number of ITSS within the lesion with P value 0.001, followed by the size of the ITSS with P value 0.002 and Pearson Chi-Square value equals 20.6, while the lowest one was the ratio of the ITSS to the tumor size with P value 0.002 Pearson Chi-Square value equals 17.3. Our study showed that the morphology alone was not able to accurately grade the tumor with P value 0.007 ( Not significant) Conclusion SWI using 3T MR system provides quite useful information for preoperative tumor grading. There seems to be a strong correlation between pathological grading and that assessed with SWI.

scholarly journals TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle

2015 ◽  
Vol 224 (3) ◽  
pp. 303-313 ◽  
Author(s):  
Jonathan M Mudry ◽  
Julie Massart ◽  
Ferenc L M Szekeres ◽  
Anna Krook
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Glycogen Synthesis ◽  
C2c12 Cells ◽  
Acid Oxidation ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Intact Mouse ◽  
Mouse Muscle ◽  
The Impact

TWIST proteins are important for development of embryonic skeletal muscle and play a role in the metabolism of tumor and white adipose tissue. The impact of TWIST on metabolism in skeletal muscle is incompletely studied. Our aim was to assess the impact of TWIST1 and TWIST2 overexpression on glucose and lipid metabolism. In intact mouse muscle, overexpression of Twist reduced total glycogen content without altering glucose uptake. Expression of TWIST1 or TWIST2 reducedPdk4mRNA, while increasing mRNA levels ofIl6,Tnfα, andIl1β. Phosphorylation of AKT was increased and protein abundance of acetyl CoA carboxylase (ACC) was decreased in skeletal muscle overexpressing TWIST1 or TWIST2. Glycogen synthesis and fatty acid oxidation remained stable in C2C12 cells overexpressing TWIST1 or TWIST2. Finally, skeletal muscle mRNA levels remain unaltered inob/obmice, type 2 diabetic patients, or in healthy subjects before and after 3 months of exercise training. Collectively, our results indicate that TWIST1 and TWIST2 are expressed in skeletal muscle. Overexpression of these proteins impacts proteins in metabolic pathways and mRNA level of cytokines. However, skeletal muscle levels of TWIST transcripts are unaltered in metabolic diseases.

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