scholarly journals Glucagon-Like Peptide-1 Modulates Cholesterol Homeostasis by Suppressing the miR-19b-Induced Downregulation of ABCA1

2018 ◽  
Vol 50 (2) ◽  
pp. 679-693 ◽  
Author(s):  
Yue Yao ◽  
Qiang Li ◽  
Wei Wang ◽  
Jinchao Zhang ◽  
Ping Gao ◽  
...  
Keyword(s):  
Cell Viability ◽  
Lipid Accumulation ◽  
Cholesterol Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Abca1 Protein

Background/Aims: Abnormal regulation of cholesterol homeostasis is associated with type 2 diabetes mellitus (T2DM) and multiple other diseases. Glucagon-like peptide-1 (GLP-1) has unique effects on modulating hepatic lipid metabolism. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. Methods: Cell viability was determined by CCK-8. Caspase-3 detection was used to assess the effects of GLP-1 on cholesterol-induced apoptosis. TNF-α and IL-6 as the inflammatory markers were measured by ELISA. The alterations of miR-19b and ATP-binding cassette transporter A1 (ABCA1) resulting from high-fat diet/cholesterol incubation or GLP-1 were detected by real-time PCR and western blot. Results: GLP-1 markedly up-regulated the expression of ABCA1 protein, but didn’t affect peroxisome proliferator-activated receptor α (PPAR-α) protein. The miR-19b levels were significantly down-regulated in GLP-1-treated groups. The inhibition and overexpression of miR-19b were established to explore the effects of a GLP-1-mediated alteration in miR-19b. Cholesterol transport assays revealed that treatment with GLP-1 alone or together with miR-19b inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Further, histological examination was used to detect lipid accumulation. Cholesterol significantly attenuated cell viability, promoted hepatic cell apoptosis, and facilitated lipid accumulation, and these effects could be reversed by GLP-1. Conclusion: GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-19b and ABCA1.

Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity

2005 ◽  
Vol 289 (3) ◽  
pp. R729-R737 ◽  
Author(s):  
Karine Proulx ◽  
Daniela Cota ◽  
Tamara R. Castañeda ◽  
Matthias H. Tschöp ◽  
David A. D'Alessio ◽  
...  
Keyword(s):  
Food Intake ◽  
Motor Activity ◽  
Peptide Yy ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein A ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Induced Changes

Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-α. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Because the anorexigenic effect of OEA is associated with delayed feeding onset and reduced locomotion, we examined whether intraperitoneal administration of OEA results in nonspecific behavioral effects that contribute to the anorexia in rats. Moreover, we determined whether circulating levels of other gut hormones are modulated by OEA and whether CCK is involved in OEA-induced anorexia. Our results indicate that OEA reduces food intake without causing a conditioned taste aversion or reducing sodium appetite. It also failed to induce a conditioned place aversion. However, OEA induced changes in posture and reduced spontaneous activity in the open field. This likely underlies the reduced heat expenditure and sodium consumption observed after OEA injection, which disappeared within 1 h. The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-α agonist Wy-14643. Plasma levels of ghrelin, peptide YY, glucagon-like peptide 1, and apolipoprotein A-IV were not changed by OEA. Finally, antagonism of CCK-1 receptors did not affect OEA-induced anorexia. These results suggest that OEA suppresses feeding without causing visceral illness and that neither ghrelin, peptide YY, glucagon-like peptide 1, apolipoprotein A-IV, nor CCK plays a critical role in this effect. Despite that OEA-induced anorexia is unlikely to be due to impaired motor activity, our data raise a cautionary note in how specific behavioral and metabolic effects of OEA should be interpreted.

Fighting Diabetes Mellitus: Pharmacological and Non-pharmacological Approaches

2020 ◽  
Vol 26 (39) ◽  
pp. 4992-5001
Author(s):  
Xin Wang ◽  
Jinhong Kang ◽  
Qing Liu ◽  
Tao Tong ◽  
Helong Quan
Keyword(s):  
Diabetes Mellitus ◽  
Signaling Pathways ◽  
Glucose Homeostasis ◽  
Diabetes Management ◽  
Lifestyle Modification ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: The increasing worldwide prevalence of diabetes mellitus confers heavy public health issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost scientific challenges. Objectives: This article aims to provide an overview of current pharmacological and non-pharmacological approaches available for the management of diabetes mellitus. Methods: Research articles that focused on pharmacological and non-pharmacological interventions for diabetes were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes, glucagon-like peptide-1, glucose homeostasis, etc. Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors- cyclic adenosine monophosphate, 5′-adenosine monophosphate-activated protein kinase, sodium-glucose cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods designed to mitigate diabetes are summarized and discussed. Conclusion: Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2 inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent the most important strategies in diabetes management. These approved diabetes medications work via targeting the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is insufficient to achieve positive outcomes.

Antidiabetics: Structural Diversity of Molecules with a Common Aim

2018 ◽  
Vol 25 (18) ◽  
pp. 2140-2165 ◽  
Author(s):  
Jelena B. Popovic-Djordjevic ◽  
Ivana I. Jevtic ◽  
Tatjana P. Stanojkovic
Keyword(s):  
Structural Diversity ◽  
World Health ◽  
Common Disease ◽  
Peroxisome Proliferator ◽  
Epidemic Disease ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Health Organization

Background: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability. Methods: A systematic search of peer-reviewed scientific literature and public databases has been conducted. We included the most recent relevant research papers and data in respect to the focus of the present review. The quality of retrieved papers was assessed using standard tools. Results: The review highlights the chemical structural diversity of the molecules that have the common target-DMT2. So-called traditional antidiabetics as well as the newest and the least explored drugs include polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1, dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives, benzylthiazolidine- 2,4-diones (peroxisome proliferator activated receptor-γ agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules (α-glucosidase and sodium/ glucose co-transporter 2 inhibitors). Conclusion: As diabetes becomes a more common disease, interest in new pharmacological targets is on the rise.

scholarly journals The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6074
Author(s):  
Maciej Danielewski ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
Tomasz Sozański
Keyword(s):  
Transcription Factors ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Functions ◽  
The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

scholarly journals The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1025
Author(s):  
Ahmed Alalaiwe ◽  
Jia-You Fang ◽  
Hsien-Ju Lee ◽  
Chun-Hui Chiu ◽  
Ching-Yun Hsu
Keyword(s):  
Molecular Docking ◽  
Fatty Acid Synthase ◽  
Structural Similarity ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

Clofibrate causes an upregulation of PPAR-α target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs

2007 ◽  
Vol 293 (1) ◽  
pp. R70-R77 ◽  
Author(s):  
Sebastian Luci ◽  
Beatrice Giemsa ◽  
Holger Kluge ◽  
Klaus Eder
Keyword(s):  
Adipose Tissue ◽  
Target Genes ◽  
Regulatory Element ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Expression

This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-α and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-α target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs ( P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes ( Insig) -1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-α in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-α activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.

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