Changes in adipokine expression during food deprivation in the mouse and the relationship to fasting-induced insulin resistance

2003 ◽  
Vol 81 (10) ◽  
pp. 979-985 ◽  
Author(s):  
Yaoting Gui ◽  
Josef V Silha ◽  
Suresh Mishra ◽  
Liam J Murphy
Keyword(s):  
Insulin Resistance ◽  
Food Deprivation ◽  
Tissue Expression ◽  
Brown Fat ◽  
Mrna Abundance ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Plasma Leptin

We investigated the changes in insulin resistance and adipose tissue expression of the adipokines resistin, adiponectin, and leptin and the transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ) and retinoid X receptor-α (RXR-α) during 48 h of food deprivation. Insulin sensitivity (SI) declined, whereas glucose effectiveness (SG) increased. Plasma adiponectin levels declined in the first 8 h and remained constant thereafter. There was no correlation between either SI or SG and adiponectin protein or mRNA levels. PPAR-γ mRNA abundance remained constant, whereas leptin and resistin mRNAs and plasma leptin declined and RXR-α mRNA abundance increased in both white and brown fat. Leptin mRNA abundance was closely correlated with SI (R2 = 0.91 and 0.87 for white and brown fat, respectively). Resistin mRNA abundance correlated inversely with SG (R2 = 0.99 and 0.84 for white and brown fat, respectively). These data indicate that changes in the expression of leptin are more closely correlated with the insulin resistance of fasting than with changes in other adipokines or RXR-α and PPAR-γ expression.Key words: insulin resistance, fasting, adipokines, resistin, leptin, adiponectin.

scholarly journals Expression of peroxisome proliferator-activated receptor-γ in macrophage suppresses experimentally induced colitis

2007 ◽  
Vol 292 (2) ◽  
pp. G657-G666 ◽  
Author(s):  
Yatrik M. Shah ◽  
Keiichirou Morimura ◽  
Frank J. Gonzalez
Keyword(s):  
Clinical Symptoms ◽  
Body Weight Loss ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Wild Type ◽  
Targeted Disruption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cytokine Analysis ◽  
Increased Susceptibility

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has been shown to be a protective transcription factor in mouse models of inflammatory bowel disease (IBD). PPAR-γ is expressed in several different cell types, and mice with a targeted disruption of the PPAR-γ gene in intestinal epithelial cells demonstrated increased susceptibility to dextran sulfate sodium (DSS)-induced IBD. However, the highly selective PPAR-γ ligand rosiglitazone decreased the severity of DSS-induced colitis and suppressed cytokine production in both PPAR-γ intestinal specific null mice and wild-type littermates. Therefore the role of PPAR-γ in different tissues and their contribution to the pathogenesis of IBD still remain unclear. Mice with a targeted disruption of PPAR-γ in macrophages (PPAR-γΔMφ) and wild-type littermates (PPAR-γF/F) were administered 2.5% DSS in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis, and proinflammatory cytokine analysis was performed. PPAR-γΔMφ mice displayed an increased susceptibility to DSS-induced colitis compared with wild-type littermates, as defined by body weight loss, diarrhea, rectal bleeding score, colon length, and histology. IL-1β, CCR2, MCP-1, and inducible nitric oxide synthase mRNA levels in colons of PPAR-γΔMφ mice treated with DSS were higher than in similarly treated PPAR-γF/F mice. The present study has identified a novel protective role for macrophage PPAR-γ in the DSS-induced IBD model. The data suggest that PPAR-γ regulates recruitment of macrophages to inflammatory foci in the colon.

Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia

2006 ◽  
Vol 291 (3) ◽  
pp. E536-E543 ◽  
Author(s):  
Chaodong Wu ◽  
Salmaan A. Khan ◽  
Li-Jen Peng ◽  
Honggui Li ◽  
Steven G. Carmella ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Insulin Resistance ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Flux ◽  
Hepatic Glucose

Hepatic insulin resistance is one of the characteristics of type 2 diabetes and contributes to the development of hyperglycemia. How changes in hepatic glucose flux lead to insulin resistance is not clearly defined. We determined the effects of decreasing the levels of hepatic fructose 2,6-bisphosphate (F26P2), a key regulator of glucose metabolism, on hepatic glucose flux in the normal 129J mice. Upon adenoviral overexpression of a kinase activity-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, the enzyme that determines F26P2 level, hepatic F26P2 levels were decreased twofold compared with those of control virus-treated mice in basal state. In addition, under hyperinsulinemic conditions, hepatic F26P2 levels were much lower than those of the control. The decrease in F26P2 leads to the elevation of basal and insulin-suppressed hepatic glucose production. Also, the efficiency of insulin to suppress hepatic glucose production was decreased (63.3 vs. 95.5% suppression of the control). At the molecular level, a decrease in insulin-stimulated Akt phosphorylation was consistent with hepatic insulin resistance. In the low hepatic F26P2 states, increases in both gluconeogenesis and glycogenolysis in the liver are responsible for elevations of hepatic glucose production and thereby contribute to the development of hyperglycemia. Additionally, the increased hepatic gluconeogenesis was associated with the elevated mRNA levels of peroxisome proliferator-activated receptor-γ coactivator-1α and phospho enolpyruvate carboxykinase. This study provides the first in vivo demonstration showing that decreasing hepatic F26P2 levels leads to increased gluconeogenesis in the liver. Taken together, the present study demonstrates that perturbation of glucose flux in the liver plays a predominant role in the development of a diabetic phenotype, as characterized by hepatic insulin resistance.

scholarly journals Novel Function of α-Cubebenoate Derived from Schisandra chinensis as Lipogenesis Inhibitor, Lipolysis Stimulator and Inflammasome Suppressor

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4995
Author(s):  
Su Ji Bae ◽  
Ji Eun Kim ◽  
Yun Ju Choi ◽  
Su Jin Lee ◽  
Jeong Eun Gong ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Protein ◽  
Fatty Acid Synthetase ◽  
Inflammasome Activation ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Schisandra Chinensis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Ppar Γ

The efficacy of α-cubebenoate isolated from Schisandra chinensis has been previously studied in three disease areas, namely inflammation, sepsis, and allergy, and its role in other diseases is still being explored. To identify the novel function of α-cubebenoate on lipid metabolism and related inflammatory response, alterations in fat accumulation, lipogenesis, lipolysis, and inflammasome activation were measured in 3T3-L1 preadipocytes and primary adipocytes treated with α-cubebenoate. Lipid accumulation significantly decreased in MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-stimulated 3T3-L1 adipocytes treated with α-cubebenoate without any significant cytotoxicity. The mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT-enhancer binding protein (C/EBP) α for adipogenesis, as well as adipocyte fatty acid binding protein 2 (aP2) and fatty acid synthetase (FAS) for lipogenesis, were reduced after α-cubebenoate treatment, while cell cycle arrest at G2/M stage was restored in the same group. α-cubebenoate treatment induced glycerol release in primary adipocytes and enhanced expression of lipolytic proteins (HSL, perilipin, and ATGL) expression in MDI-stimulated 3T3-L1 adipocytes. Inflammasome activation and downstream cytokines expression were suppressed with α-cubebenoate treatment, but the expression of insulin receptor signaling factors was remarkably increased by α-cubebenoate treatment in MDI-stimulated 3T3-L1 adipocytes. These results indicate that α-cubebenoate may play a novel role as lipogenesis inhibitor, lipolysis stimulator, and inflammasome suppressor in MDI-stimulated 3T3-L1 adipocytes. Our results provide the possibility that α-cubebenoate can be considered as one of the candidates for obesity management.

Rosiglitazone Reduces the Evolution of Experimental Periodontitis in the Rat

2006 ◽  
Vol 85 (2) ◽  
pp. 156-161 ◽  
Author(s):  
R. Di Paola ◽  
E. Mazzon ◽  
D. Maiere ◽  
D. Zito ◽  
D. Britti ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Alveolar Bone ◽  
Bone Destruction ◽  
Neutrophil Infiltration ◽  
Tissue Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Periodontal Inflammation ◽  
Experimental Periodontitis

The peroxisome proliferator-activated receptor-γ (PPAR-γ) receptor appears to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that rosiglitazone, a PPAR-γ agonist, reduces acute and chronic inflammation. We hypothesized that rosiglitazone would attenuate periodontal inflammation. In the present study, we investigated the effects of rosiglitazone in a rat model of ligature-induced periodontitis. At day 8, ligation significantly induced an increase in neutrophil infiltration, as well as of gingivomucosal tissue expression of iNOS, nitrotyrosine formation, and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of rosiglitazone (10 mg/kg 10% DMSO daily for 8 days) significantly decreased all of the parameters of inflammation, as described above. Analysis of these data demonstrated that rosiglitazone exerted an anti-inflammatory role during experimental periodontitis, and was able to ameliorate the tissue damage associated with ligature-induced periodontitis.

Peroxisome proliferator-activated receptor-γ ligands regulate endothelial membrane superoxide production

2005 ◽  
Vol 288 (4) ◽  
pp. C899-C905 ◽  
Author(s):  
Jinah Hwang ◽  
Dean J. Kleinhenz ◽  
Bernard Lassègue ◽  
Kathy K. Griendling ◽  
Sergey Dikalov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Pcr Analysis ◽  
Resonance Spectroscopy ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Endothelial Nitric Oxide

Recently, we demonstrated that the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands, either 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) or ciglitazone, increased endothelial nitric oxide (·NO) release without altering endothelial nitric oxide synthase (eNOS) expression ( 4 ). However, the precise molecular mechanisms of PPAR-γ-stimulated endothelial·NO release remain to be defined. Superoxide anion radical (O2−·) combines with ·NO to decrease·NO bioavailability. NADPH oxidase, which produces O2−·, and Cu/Zn-superoxide dismutase (Cu/Zn-SOD), which degrades O2−·, thereby contribute to regulation of endothelial cell·NO metabolism. Therefore, we examined the ability of PPAR-γ ligands to modulate endothelial O2−· metabolism through alterations in the expression and activity of NADPH oxidase or Cu/Zn-SOD. Treatment with 10 μM 15d-PGJ2 or ciglitazone for 24 h decreased human umbilical vein endothelial cell (HUVEC) membrane NADPH-dependent O2−· production detected with electron spin resonance spectroscopy. Treatment with 15d-PGJ2 or ciglitazone also reduced relative mRNA levels of the NADPH oxidase subunits, nox-1, gp91 phox (nox-2), and nox-4, as measured using real-time PCR analysis. Concordantly, Western blot analysis demonstrated that 15d-PGJ2 or ciglitazone decreased nox-2 and nox-4 protein expression. PPAR-γ ligands also stimulated both activity and expression of Cu/Zn-SOD in HUVEC. These data suggest that in addition to any direct effects on endothelial·NO production, PPAR-γ ligands enhance endothelial·NO bioavailability, in part by altering endothelial O2−· metabolism through suppression of NADPH oxidase and induction of Cu/Zn-SOD. These findings further elucidate the molecular mechanisms by which PPAR-γ ligands directly alter vascular endothelial function.

Use of Pioglitazone in Patients with Lichen Planopilaris

2012 ◽  
Vol 16 (2) ◽  
pp. 97-100 ◽  
Author(s):  
Akerke Baibergenova ◽  
Scott Walsh
Keyword(s):  
Side Effects ◽  
Science Research ◽  
Tissue Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lichen Planopilaris ◽  
Ppar Γ ◽  
Pparγ Agonists ◽  
Left Calf ◽  
Calf Pain

Background: Recent basic science research has revealed a decreased tissue expression of peroxisome proliferator-activated receptor (PPAR) γ in lichen planopilaris (LPP). Therefore, thiazolidinediones, being PPARγ agonists, could be used to treat LPP. Methods: We followed 24 patients with LPP who were treated with oral pioglitazone hydrochloride. Improvement in LPP was defined as a decrease in or disappearance of symptoms and perifollicular erythema in the context of halted spread of old patches. Results: Twenty of 24 patients were females. The average age was 52.5 years, and ages ranged from 22 to 70 years. Five of 24 patients have achieved remission; improvement was noted in half of the patients; there was no change in 3 patients; and 4 patients discontinued treatment due to side effects. Side effects were mild and included left calf pain, lightheadedness and nausea, dizziness, and hives. Conclusion: Use of thiazolidinediones might be a new promising venue of LPP treatment.

scholarly journals Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart

2005 ◽  
Vol 385 (2) ◽  
pp. 469-477 ◽  
Author(s):  
Biao LU ◽  
Yan J. JIANG ◽  
Yaling ZHOU ◽  
Fred Y. XU ◽  
Grant M. HATCH ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Tissue Expression ◽  
In Vitro Transcription ◽  
Amino Acid Sequences ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor

AGPAT (1-acyl-sn-glycerol 3-phosphate acyltransferase) exists in at least five isoforms in humans, termed as AGPAT1, AGPAT2, AGPAT3, AGPAT4 and AGPAT5. Although they catalyse the same biochemical reaction, their relative function, tissue expression and regulation are poorly understood. Linkage studies in humans have revealed that AGPAT2 contributes to glycerolipid synthesis and plays an important role in regulating lipid metabolism. We report the molecular cloning, tissue distribution, and enzyme characterization of mAGPATs (murine AGPATs) and regulation of cardiac mAGPATs by PPARα (peroxisome-proliferator-activated receptor α). mAGPATs demonstrated differential tissue expression profiles: mAGPAT1 and mAGPAT3 were ubiquitously expressed in most tissues, whereas mAGPAT2, mAGPAT4 and mAGPAT5 were expressed in a tissue-specific manner. mAGPAT2 expressed in in vitro transcription and translation reactions and in transfected COS-1 cells exhibited specificity for 1-acyl-sn-glycerol 3-phosphate. When amino acid sequences of five mAGPATs were compared, three highly conserved motifs were identified, including one novel motif/pattern KX2LX6GX12R. Cardiac mAGPAT activities were 25% lower (P<0.05) in PPARα null mice compared with wild-type. In addition, cardiac mAGPAT activities were 50% lower (P<0.05) in PPARα null mice fed clofibrate compared with clofibrate fed wild-type animals. This modulation of AGPAT activity was accompanied by significant enhancement/reduction of the mRNA levels of mAGPAT3/mAGPAT2 respectively. Finally, mRNA expression of cardiac mAGPAT3 appeared to be regulated by PPARα activation. We conclude that cardiac mAGPAT activity may be regulated by both the composition of mAGPAT isoforms and the levels of each isoform.

scholarly journals Improvement of Insulin Sensitivity after Peroxisome Proliferator-Activated Receptor-α Agonist Treatment Is Accompanied by Paradoxical Increase of Circulating Resistin Levels

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4517-4524 ◽  
Author(s):  
M. M. Haluzik ◽  
Z. Lacinova ◽  
M. Dolinkova ◽  
D. Haluzikova ◽  
D. Housa ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Liver Steatosis ◽  
Tissue Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Levels ◽  
Fenofibrate Treatment ◽  
Adiponectin Mrna

We studied the effect of peroxisome proliferator-activated receptor-α (PPAR-α) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-α agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-α activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.

Thiazolidinedione-induced effects beyond glycaemic control

2002 ◽  
Vol 2 (1_suppl) ◽  
pp. S24-S27 ◽  
Author(s):  
Ulf Smith
Keyword(s):  
Insulin Resistance ◽  
Nuclear Receptors ◽  
Tumour Necrosis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Tumour Necrosis Factor Α ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Factor Α ◽  
Necrosis Factor

The thiazolidinediones exert their insulin sensitising effect by binding to the nuclear receptors (transcription factors) peroxisome proliferator activated receptor (PPAR) γ and, to varying degrees, to PPARα. Several different genes are activated by thiazolidinediones, many of which contribute to the increase in insulin sensitivity (eg. an increase in glucose uptake and utilisation, a decrease in gluconeogenesis and in insulin-antagonistic cytokines, such as tumour necrosis factor α). Activation of other genes indirectly reduces insulin resistance by, for example, increasing free fatty acid (FFA) uptake and oxidation resulting in lower circulating FFA levels. The action of thiazolidinediones at PPARγ is generally responsible for their insulin sensitising effects while action at PPARα contributes to their lipid lowering effects. Therefore, the relative affinities of the different thiazolidinediones for PPARγ and PPARα will also lead to a different spectrum of actions for each agent.

scholarly journals Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression—A Literature Review

2020 ◽  
Vol 21 (18) ◽  
pp. 6969
Author(s):  
Young Sup Woo ◽  
Hyun Kook Lim ◽  
Sheng-Min Wang ◽  
Won-Myong Bahk
Keyword(s):  
Insulin Resistance ◽  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Antidepressant Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Glucagon Like Peptide 1 ◽  
Review Reports

Close connections between depression and type 2 diabetes (T2DM) have been suggested by many epidemiological and experimental studies. Disturbances in insulin sensitivity due to the disruption of various molecular pathways cause insulin resistance, which underpins many metabolic disorders, including diabetes, as well as depression. Several anti-hyperglycemic agents have demonstrated antidepressant properties in clinical trials, probably due to their action on brain targets based on the shared pathophysiology of depression and T2DM. In this article, we review reports of clinical trials examining the antidepressant effect of these medications, including insulin, metformin, glucagon like peptide-1 receptor agonists (GLP-1RA), and peroxisome proliferator-activated receptor (PPAR)-γ agonists, and briefly consider possible molecular mechanisms underlying the associations between amelioration of insulin resistance and improvement of depressive symptoms. In doing so, we intend to suggest an integrative perspective for understanding the pathophysiology of depression.

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