scholarly journals Purified Gymnemic Acids from Gymnema inodorum Tea Inhibit 3T3-L1 Cell Differentiation into Adipocytes

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2851
Author(s):  
Papawee Saiki ◽  
Yasuhiro Kawano ◽  
Takayuki Ogi ◽  
Prapaipat Klungsupya ◽  
Thanchanok Muangman ◽  
...  
Keyword(s):  
Early Stage ◽  
Uncoupling Protein ◽  
Glucose Absorption ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Preadipocyte Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Healthy Humans ◽  
Medicinal Properties

Gymnema inodorum (GI) is an indigenous medicinal plant and functional food in Thailand that has recently helped to reduce plasma glucose levels in healthy humans. It is renowned for the medicinal properties of gymnemic acid and its ability to suppress glucose absorption. However, the effects of gymnemic acids on adipogenesis that contribute to the accumulation of adipose tissues associated with obesity remain unknown. The present study aimed to determine the effects of gymnemic acids derived from GI tea on adipogenesis. We purified and identified GiA-7 and stephanosides C and B from GI tea that inhibited adipocyte differentiation in 3T3-L1 cells. These compounds also suppressed the expression of peroxisome proliferator-activated receptor gamma (Pparγ)-dependent genes, indicating that they inhibit lipid accumulation and the early stage of 3T3-L1 preadipocyte differentiation. Only GiA-7 induced the expression of uncoupling protein 1 (Ucp1) and pparγ coactivator 1 alpha (Pgc1α), suggesting that GiA-7 induces mitochondrial activity and beige-like adipocytes. This is the first finding of stephanosides C and B in Gymnema inodorum. Our results suggested that GiA-7 and stephanosides C and B from GI tea could help to prevent obesity.

scholarly journals Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy

2020 ◽  
Vol 21 (17) ◽  
pp. 6243 ◽  
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Yukihiro Miwa ◽  
Xiaoyan Jiang ◽  
Masayuki Ohta ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Blood Glucose ◽  
Vision Loss ◽  
Early Stage ◽  
Neural Function ◽  
Peroxisome Proliferator ◽  
Diabetic Mice ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Adult Mice

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.

scholarly journals Bilirubin remodels murine white adipose tissue by reshaping mitochondrial activity and the coregulator profile of peroxisome proliferator–activated receptor α

2020 ◽  
Vol 295 (29) ◽  
pp. 9804-9822 ◽  
Author(s):  
Darren M. Gordon ◽  
Kari L. Neifer ◽  
Abdul-Rizaq Ali Hamoud ◽  
Charles F. Hawk ◽  
Andrea L. Nestor-Kalinoski ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Target Genes ◽  
Uncoupling Protein ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes ◽  
Selective Ligand ◽  
Related Proteins

Activation of lipid-burning pathways in the fat-storing white adipose tissue (WAT) is a promising strategy to improve metabolic health and reduce obesity, insulin resistance, and type II diabetes. For unknown reasons, bilirubin levels are negatively associated with obesity and diabetes. Here, using mice and an array of approaches, including MRI to assess body composition, biochemical assays to measure bilirubin and fatty acids, MitoTracker-based mitochondrial analysis, immunofluorescence, and high-throughput coregulator analysis, we show that bilirubin functions as a molecular switch for the nuclear receptor transcription factor peroxisome proliferator–activated receptor α (PPARα). Bilirubin exerted its effects by recruiting and dissociating specific coregulators in WAT, driving the expression of PPARα target genes such as uncoupling protein 1 (Ucp1) and adrenoreceptor β 3 (Adrb3). We also found that bilirubin is a selective ligand for PPARα and does not affect the activities of the related proteins PPARγ and PPARδ. We further found that diet-induced obese mice with mild hyperbilirubinemia have reduced WAT size and an increased number of mitochondria, associated with a restructuring of PPARα-binding coregulators. We conclude that bilirubin strongly affects organismal body weight by reshaping the PPARα coregulator profile, remodeling WAT to improve metabolic function, and reducing fat accumulation.

scholarly journals Polymorphisms in LEPR, PPARG and APM1 genes: associations with energy intake and metabolic traits in young children

2013 ◽  
Vol 57 (8) ◽  
pp. 603-611 ◽  
Author(s):  
Marília Remuzzi Zandoná ◽  
Raquel Olmedo Rodrigues ◽  
Gabriela Albiero ◽  
Paula Dal Bó Campagnolo ◽  
Márcia Regina Vitolo ◽  
...  
Keyword(s):  
Energy Intake ◽  
Leptin Receptor ◽  
Linear Models ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Test Analysis ◽  
Single Nucleotide ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) in five genes - leptin, leptin receptor (LEPR), adiponectin (APM1), peroxisome proliferator-activated receptor gamma (PPARG) and uncoupling protein 1 - with anthropometric, metabolic, and dietary parameters in a Southern Brazilian cohort of 325 children followed up from birth to 4 years old. MATERIALS AND METHODS: SNPs were analyzed using polymerase chain reaction-based procedures, and their association with phenotypes was evaluated by t-test, analysis of variance, and general linear models. RESULTS: LEPR223Arg allele (rs1137101) was associated with higher daily energy intake at 4 years of age (P = 0.002; Pcorrected = 0.024). PPARG 12Ala-carriers (rs1801282) presented higher glucose levels than Pro/Pro homozygotes (P = 0.007; Pcorrected = 0.042). CONCLUSIONS: Two of the six studied SNPs presented consistent associations, showing that it is already possible to detect the influences of genetic variants on susceptibility to overweight in 4-year-old children.

scholarly journals Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice

2017 ◽  
Vol 312 (5) ◽  
pp. E394-E406 ◽  
Author(s):  
Samuel Lee ◽  
Teresa C. Leone ◽  
Lisa Rogosa ◽  
John Rumsey ◽  
Julio Ayala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Early Stage ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Proof Of Concept ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Training Response

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.

scholarly journals Pancreatic Islet Adaptation to Fasting Is Dependent on Peroxisome Proliferator-Activated Receptor α Transcriptional Up-Regulation of Fatty Acid Oxidation

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 375-382 ◽  
Author(s):  
Sandrine Gremlich ◽  
Christopher Nolan ◽  
Raphaël Roduit ◽  
Rémy Burcelin ◽  
Marie-Line Peyot ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pancreatic Islet ◽  
Cellular Response ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Hyperinsulinemic Hypoglycemia ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and liver requires peroxisome proliferator-activated receptor-α (PPARα)-dependent up-regulation of energy metabolism toward fatty acid oxidation (FAO). PPARα null (PPARαKO) mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed that PPARα expression is increased in islets at low glucose. On this basis, we hypothesized that enhanced PPARα expression and FAO, via depletion of lipid-signaling molecule(s) for insulin exocytosis, are also involved in the normal adaptive response of the islet to fasting. Fasted PPARαKO mice compared with wild-type mice had supranormal ip glucose tolerance due to increased plasma insulin levels. Isolated islets from the PPARα null mice had a 44% reduction in FAO, normal glucose use and oxidation, and enhanced glucose-induced insulin secretion. In normal rats, fasting for 24 h increased islet PPARα, carnitine palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and 82%, respectively. The data are consistent with the view that PPARα, via transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that this mechanism is involved in the normal physiological response of the pancreatic islet to fasting such that hypoglycemia is avoided.

scholarly journals Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110550
Author(s):  
Xing Wang ◽  
Shuchun Chen ◽  
Dan Lv ◽  
Zelin Li ◽  
Luping Ren ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
White Adipocytes ◽  
White Fat

Objective To investigate the effect of liraglutide on the browning of white fat and the suppression of obesity via regulating microRNA (miR)-27b in vivo and in vitro. Methods Sprague-Dawley rats were fed a high-fat (HF) diet and 3T3-L1 pre-adipocytes were differentiated into mature white adipocytes. Rats and mature adipocytes were then treated with different doses of liraglutide. The mRNA and protein levels of browning-associated proteins, including uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), CCAAT enhancer binding protein β (CEBPβ), cell death-inducing DFFA-like effector A (CIDEA) and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), were detected using quantitative real-time polymerase chain reaction and Western blotting. Results Liraglutide decreased body weight and reduced the levels of blood glucose, triglyceride and low-density lipoprotein cholesterol in HF diet-fed rats. Liraglutide increased the levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α in vivo and vitro. The levels of miR-27b were upregulated in HF diet-fed rats, whereas liraglutide reduced the levels of miR-27b. In vitro, overexpression of miR-27b decreased the mRNA and protein levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α. Transfection with the miR-27b mimics attenuated the effect of liraglutide on the browning of white adipocytes. Conclusion Liraglutide induced browning of white adipose through regulation of miR-27b.

scholarly journals BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes

2020 ◽  
Vol 3 (9) ◽  
pp. e201900619
Author(s):  
Hyoung Kyu Kim ◽  
Tae Hee Ko ◽  
In-Sung Song ◽  
Yu Jeong Jeong ◽  
Hye Jin Heo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Therapeutic Potential ◽  
Cardiac Contractility ◽  
Camp Response Element Binding ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Calcium Calmodulin Dependent ◽  
Element Binding Protein ◽  
Underlying Mechanisms

Diabetic cardiomyopathy (DCM) is a major cause of mortality/morbidity in diabetes mellitus patients. Although tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous cardiovascular target, its effect on myocardial cells and mitochondria in DCM and the underlying mechanisms remain unknown. Here, we determined the involvement of BH4 deficiency in DCM and the therapeutic potential of BH4 supplementation in a rodent DCM model. We observed a decreased BH4:total biopterin ratio in heart and mitochondria accompanied by cardiac remodeling, lower cardiac contractility, and mitochondrial dysfunction. Prolonged BH4 supplementation improved cardiac function, corrected morphological abnormalities in cardiac muscle, and increased mitochondrial activity. Proteomics analysis revealed oxidative phosphorylation (OXPHOS) as the BH4-targeted biological pathway in diabetic hearts as well as BH4-mediated rescue of down-regulated peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) signaling as a key modulator of OXPHOS and mitochondrial biogenesis. Mechanistically, BH4 bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and activated downstream AMP-activated protein kinase/cAMP response element binding protein/PGC-1α signaling to rescue mitochondrial and cardiac dysfunction in DCM. These results suggest BH4 as a novel endogenous activator of CaMKK2.

scholarly journals Peroxisome Proliferator-Activated Receptor α (PPARα) Potentiates, whereas PPARγ Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3266-3276 ◽  
Author(s):  
Kim Ravnskjaer ◽  
Michael Boergesen ◽  
Blanca Rubi ◽  
Jan K. Larsen ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Stimulated Insulin Secretion

Abstract Fatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic β-cells. FA-coenzyme A esters have been shown to directly stimulate the secretion process, whereas long-term exposure of β-cells to FAs compromises glucose-stimulated insulin secretion (GSIS) by mechanisms unknown to date. It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2). In this study we show that adenoviral coexpression of PPARα and retinoid X receptor α (RXRα) in INS-1E β-cells synergistically and in a dose- and ligand-dependent manner increases the expression of known PPARα target genes and enhances FA uptake and β-oxidation. In contrast, ectopic expression of PPARγ/RXRα increases FA uptake and deposition as triacylglycerides. Although the expression of PPARα/RXRα leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient. Importantly, whereas expression of PPARγ/RXRα attenuates GSIS, the expression of PPARα/RXRα potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential. These results show a strong subtype specificity of the two PPAR subtypes α and γ on lipid partitioning and insulin secretion when systematically compared in a β-cell context.

Abstract P172: Activation of Pgc1α by EET Stimulates Insulin Sensitivity, Normalizes Blood Pressure and Increases Mitochondrial Oxphos in Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Shailendra P Singh ◽  
Maayan Waldman ◽  
Joseph Schragenheim ◽  
Lars Bellner ◽  
Jian Cao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Fasting Blood Glucose ◽  
Cardiovascular Complications ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Obesity In Mice

Background/Objectives: Obesity is a risk factor in the development of type 2 diabetes mellitus (DM2), which is associated with increased morbidity and mortality, predominantly as a result of cardiovascular complications. Increased adiposity is a systemic condition characterized by increased oxidative stress (ROS), inflammation, inhibition of anti-oxidant genes such as HO-1 and increased degradation of epoxyeicosatrienoic acids (EETs). Hypothesis: We postulate that EETs increase peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) activity, which controls mitochondrial function, oxidative metabolism and may also increase antioxidants and HO-1 gene expression. Methods: C57/B16 mice were fed a high fat (HF) diet for 26 wks. The protocol comprised three groups: A) WT, B) HF control and C) HF-treated with EET agonist (EET-A). Renal and visceral fat tissues were harvested to measure signaling protein. Consumption was measured at 6 and 24 wks. Mice were used to assess insulin levels, insulin sensitivity, blood pressure and mitochondrial OXPHOS and mitochondrial biogenesis (Mfn1, 2 and Opa1), and oxygen consumption (VO 2 ). Results: Animals on a HF diet exhibited increased body weight, fat content, fasting blood glucose levels, systolic blood pressure (BP) and a significant reduction in VO 2 . Administration of EET-A to HF-fed mice decreased the RQ (VCO 2 /VO 2 ) ratio and normalized BP. The HF diet produced increased levels of the adipogenic markers MEST, aP2, C/EBPα and FAS. EET-A attenuated these perturbations through an increase in renal and adipose tissue PGC1α levels. The EET-mediated HO-1 induction increased mitochondrial function as measured by OXPHOS, MnSOD and thermogenic genes, TFAM, UCP1 and SIRT 1. EET-A also increased adiponectin levels, and insulin receptor phosphorylation IRP Tyr 972 and 1146 and normalized glucose levels. Conclusion: These data show that an EET agonist increased PGC-1α-HO-1 levels thereby providing metabolic protection and increased VO 2 consumption in HF-induced obesity in mice. This novel finding suggests that the EET-mediated PGC-1α activation is essential to increase HO-1 levels, mitochondrial biogenesis, and to decrease mitochondrial ROS and adiposity.

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