scholarly journals The Role of Fructose in Non-Alcoholic Steatohepatitis: Old Relationship and New Insights

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1314
Author(s):  
Alessandro Federico ◽  
Valerio Rosato ◽  
Mario Masarone ◽  
Pietro Torre ◽  
Marcello Dallio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Fatty Acid Production ◽  
Alcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Dietary Fructose ◽  
Hepatic Fat ◽  
Fat Removal ◽  
Simple Sugar

Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers

2021 ◽  
Vol 23 ◽  
Author(s):  
Mohsen Sheykhhasan ◽  
Yaghoub Ahmadyousefi ◽  
Reihaneh Seyedebrahimi ◽  
Hamid Tanzadehpanah ◽  
Hamed Manoochehri ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Critical Analysis ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Biological Functions ◽  
Initial Development ◽  
Human Cancers ◽  
Expression Of Genes ◽  
Non Coding Rnas ◽  
Research Studies

Abstract Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

scholarly journals Dietary determinants of hepatic fat content and insulin resistance in overweight/obese children: a cross-sectional analysis of the Prevention of Diabetes in Kids (PREDIKID) study

2019 ◽  
Vol 121 (10) ◽  
pp. 1158-1165 ◽  
Author(s):  
Lide Arenaza ◽  
María Medrano ◽  
Maddi Oses ◽  
Inge Huybrechts ◽  
Ignacio Díez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dietary Intake ◽  
Dietary Habits ◽  
Sugar Content ◽  
Model Assessment ◽  
Obese Children ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Sugar Intake ◽  
Hepatic Fat

AbstractPaediatric non-alcoholic fatty liver disease has increased in parallel with childhood obesity. Dietary habits, particularly products rich in sugars, may influence both hepatic fat and insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR)). The aim of the study was to examine the association of the consumption of foods and food components, dairy desserts and substitutes (DDS), sugar-sweetened beverages (SSB), as well as total and added sugars, with hepatic fat and HOMA-IR. Dietary intake (two non-consecutive 24 h-recalls), hepatic fat (MRI) and HOMA-IR were assessed in 110 overweight/obese children (10·6 (sd 1·1) years old). Linear regression analyses were used to examine the association of dietary intake with hepatic fat and HOMA-IR adjusted for potential confounders (sex, age, energy intake, maternal educational level, total and abdominal adiposity and sugar intake). The results showed that there was a negative association between cereal intake and hepatic fat (β=–0·197, P<0·05). In contrast, both SSB consumption (β=0·217; P=0·028) and sugar in SSB (β=0·210, P=0·035), but not DDS or sugar in DDS or other dietary components, were positively associated with hepatic fat regardless of potential confounders including total sugar intake. In conclusion, cereal intake might decrease hepatic fat, whereas SSB consumption and its sugar content may increase the likelihood of having hepatic steatosis. Although these observations need to be confirmed using experimental evidence, these results suggest that healthy lifestyle intervention programs are needed to improve dietary habits as well as to increase the awareness of the detrimental effects of SSB consumption early in life.

scholarly journals miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 203 ◽  
Author(s):  
Adele Vivacqua ◽  
Anna Sebastiani ◽  
Anna Miglietta ◽  
Damiano Rigiracciolo ◽  
Francesca Cirillo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cancer Associated Fibroblasts ◽  
Breast Cancer Patients ◽  
Expression Of Genes ◽  
Taqman Array

Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. By METABRIC database analysis we ascertained that miR-338-3p positively correlates with overall survival in breast cancer patients, according to previous studies showing that miR-338-3p may suppress the growth and invasion of different cancer cells. Well-fitting with these data, a miR-338-3p mimic sequence decreased and a miR-338-3p inhibitor sequence rescued the expression of genes and the proliferative effects induced by E2 through GPER in SkBr3 cancer cells and CAFs. Altogether, our results provide novel evidence on the molecular mechanisms by which E2 may regulate miR-338-3p toward breast cancer progression.

scholarly journals Sarcopenic Obesity, Insulin Resistance, and Their Implications in Cardiovascular and Metabolic Consequences

2020 ◽  
Vol 21 (2) ◽  
pp. 494 ◽  
Author(s):  
So-hyeon Hong ◽  
Kyung Mook Choi
Keyword(s):  
Insulin Resistance ◽  
Molecular Mechanisms ◽  
Sarcopenic Obesity ◽  
Alcoholic Fatty Liver ◽  
Impaired Insulin ◽  
Aging Populations ◽  
The Impact ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

The prevalence of sarcopenic obesity is increasing worldwide, particularly amongst aging populations. Insulin resistance is the core mechanism of sarcopenic obesity and is also associated with variable cardiometabolic diseases such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Fat accumulation in muscle tissue promotes a proinflammatory cascade and oxidative stress, leading to mitochondrial dysfunction, impaired insulin signaling, and muscle atrophy. To compound the problem, decreased muscle mass aggravates insulin resistance. In addition, the crosstalk between myokines and adipokines leads to negative feedback, which in turn aggravates sarcopenic obesity and insulin resistance. In this review, we focus on the molecular mechanisms linking sarcopenic obesity and insulin resistance with various biological pathways. We also discuss the impact and mechanism of sarcopenic obesity and insulin resistance on cardiometabolic disease.

scholarly journals Arid1a protects against hepatic steatosis and insulin resistance via PPARα-mediated fatty acid oxidation

2019 ◽  
Author(s):  
Yu-Lan Qu ◽  
Chuan-Huai Deng ◽  
Qing Luo ◽  
Xue-Ying Shang ◽  
Jiao-Xiang Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Lifestyle Changes ◽  
Health Concern ◽  
Acid Oxidation ◽  
Alcoholic Fatty Liver

AbstractNon-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have become a worldwide health concern because of lifestyle changes, but it is still lack of specific therapeutic strategies as the underlying molecular mechanisms remain poorly understood. Our previous study indicated that deficiency of Arid1a, a key component of SWI/SNF chromatin remodeling complex, initiated mouse steatohepatitis, implying that Arid1a might be essentially required for the integrity of hepatic lipid metabolism. However, the exact mechanisms of the pathological process due to Arid1a loss are unclear. In the present work, we show that hepatocyte-specific deletion of Arid1a significantly increases susceptibility to develop hepatic steatosis and insulin resistance in mice fed with high-fat diet (HFD), along with the aggravated inflammatory responses marked by increment of serum alanine amino transferase (AST), aspartate amino transferase (AST) and TNFα. Mechanistically, Arid1a deficiency leads to the reduction of chromatin modification characteristic of transcriptional activation on multiple metabolic genes, especially Cpt1a and Acox1, two rate-limiting enzyme genes for fatty acid oxidation. Furthermore, our data indicated that Arid1a loss promotes hepatic steatosis by downregulating PPARα, thereby impairing fatty acid oxidation which leads to lipid accumulation and insulin resistance. These findings reveal that targeting ARID1a might be a promising therapeutic strategy for NAFLD, NASH and insulin resistance.

scholarly journals The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 321 ◽  
Author(s):  
Mayara C. F. Gewehr ◽  
Alexandre A. S. Teixeira ◽  
Bruna A. C. Santos ◽  
Luana A. Biondo ◽  
Fábio C. Gozzo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Liver Steatosis ◽  
Alcoholic Fatty Liver ◽  
Metabolism Regulation ◽  
Diet Induced Obesity ◽  
Expression Of Genes ◽  
Thimet Oligopeptidase ◽  
Functional Peptides

Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1−/−) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1−/− and WT mice ingested similar chow and calories; however, the THOP1−/− mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1−/− mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1−/− fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1−/− mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously anticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.

scholarly journals Energy Expenditure Improved Risk Factors Associated with Renal Function Loss in NAFLD and MetS Patients

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 629
Author(s):  
Manuela Abbate ◽  
Catalina M. Mascaró ◽  
Sofía Montemayor ◽  
María Barbería-Latasa ◽  
Miguel Casares ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Energy Expenditure ◽  
Controlled Trial ◽  
Caloric Intake ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Treatment Groups ◽  
Conventional Diet ◽  
Hepatic Fat ◽  
Activity Groups

To assess the efficacy of three lifestyle interventions on the reduction of liver fat content and metabolic syndrome (MetS), and whether such reductions would influence renal outcomes, we conducted a randomized controlled trial on 128 participants with MetS and non-alcoholic fatty liver disease (NAFLD), as well as available data on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR). Patients were randomized in 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)–high meal frequency, and MD–physical activity groups. Each intervention aimed at reducing caloric intake by 25%–30% of baseline intake and increase energy expenditure by 400 kcal/70 kg. Patients attended regular visits and were followed-up for 6 months. Increased albuminuria was present in 13.3% of patients, while 32.8% showed hyperfiltration. UACR reduction was associated with higher levels of UACR at baseline but not with changes in liver fat. eGFR decreased in patients presenting hyperfiltration at baseline and was associated with reduction in liver fat and insulin resistance, as well as with increase in energy expenditure (R2 = 0.248, p = 0.006). No significant differences were observed between the three treatment groups. In patients with NAFLD and MetS, energy expenditure significantly reduced hepatic fat accumulation and insulin resistance, which reduced glomerular hyperfiltration. Increased albuminuria was reduced, but it was not associated with reduced liver fat.

scholarly journals Molecular Mechanisms of Insulin Resistance Development

2014 ◽  
Vol 17 (2) ◽  
pp. 29-40 ◽  
Author(s):  
Vsevolod Arsen'evich Tkachuk ◽  
Alexander Vyacheslavovich Vorotnikov
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Blood Glucose ◽  
Molecular Mechanisms ◽  
The Body ◽  
Target Cells ◽  
Endocrine Regulation ◽  
High Blood Glucose ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Insulin resistance (IR) is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion. IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell). Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades. This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

Sign in / Sign up

Export Citation Format

Share Document