scholarly journals Skeletal Effects of the Saturated 3-Thia Fatty Acid Tetradecylthioacetic Acid in Rats

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Astrid Kamilla Stunes ◽  
Irene Westbroek ◽  
Reidar Fossmark ◽  
Rolf Kristian Berge ◽  
Janne Elin Reseland ◽  
...  
Keyword(s):  
Whole Body ◽  
Sham Operation ◽  
Peroxisome Proliferator ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Trabecular Thickness ◽  
Tetradecylthioacetic Acid ◽  
Femoral Metaphysis ◽  
Skeletal Effects

This study explores the skeletal effects of the peroxisome proliferator activated receptor (PPAR)pan agonist tetradecylthioacetic acid (TTA). Rats, without (Study I) and with ovariectomy (OVX) or sham operation (Study II), were given TTA or vehicle daily for 4 months. Bone markers in plasma, whole body and femoral bone mineral density and content (BMD and BMC), and body composition were examined. Histomorphometric and biomechanical analyses (Study I) and biomechanical and μCT analyses (Study II) of the femur were performed. Normal rats fed TTA had higher femoral BMD and increased total and cortical area in femur compared to controls. The ovariectomized groups had decreased BMD and impaired microarchitecture parameters compared to SHAM. However, the TTA OVX group maintained femoral BMC, trabecular thickness in the femoral head, and cortical volume in the femoral metaphysis as SHAM. TTA might increase BMD and exert a light preventive effect on estrogen-related bone loss in rats.

scholarly journals Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
KyeongJin Kim ◽  
Jin Ku Kang ◽  
Young Hoon Jung ◽  
Sang Bae Lee ◽  
Raffaela Rametta ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Whole Body ◽  
Acid Oxidation ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Ph Domain ◽  
Peroxisome Proliferator Activated Receptor

AbstractIncreased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.

scholarly journals The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 734
Author(s):  
Pietro Antonuccio ◽  
Herbert Ryan Marini ◽  
Antonio Micali ◽  
Carmelo Romeo ◽  
Roberta Granese ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Therapeutic Targets ◽  
Sham Operation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pyrin Domain ◽  
Age Related ◽  
Extracellular Signal ◽  
Morphometric Assessment

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.

scholarly journals Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse

2012 ◽  
Vol 26 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Kristin A. Anderson ◽  
Fumin Lin ◽  
Thomas J. Ribar ◽  
Robert D. Stevens ◽  
Michael J. Muehlbauer ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Dependent Protein Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Protein

Abstract Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2floxed mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.

Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

2003 ◽  
Vol 375 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Lise MADSEN ◽  
Rasmus K. PETERSEN ◽  
Morten B. SØRENSEN ◽  
Claus JØRGENSEN ◽  
Philip HALLENBORG ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Critical Evaluation ◽  
Nordihydroguaiaretic Acid ◽  
Whole Body ◽  
Transcriptional Networks ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Differentiation Process ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARγ (peroxisome proliferator-activated receptor γ) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARγ ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARγ ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3–4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARγ ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.

scholarly journals The Effect of Diabetes Mellitus, Insulin, and Thiazolidinediones on Bone Histomorphometry in Streptozotocin-induced Diabetic Postmenopausal Wistar Rats

2021 ◽  
pp. 56-69
Author(s):  
Derya Köseoğlu ◽  
Gülnur Take ◽  
Banu Aktaş Yılmaz ◽  
Erdal Kan ◽  
Nuri Çakır
Keyword(s):  
Diabetes Mellitus ◽  
Bone Histomorphometry ◽  
Wistar Rats ◽  
Treated Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Trabecular Thickness ◽  
Skeletal Disease ◽  
Negative Effect

Background: Osteoporosis is a metabolic skeletal disease with low bone mass and bone microarchitectural disorganization. Thiazolidinediones (TZD) increase insulin sensitivity through activation of peroxisome proliferator-activated receptor gamma (PPARγ). One of the most important side effects of this drugs is its effects on bone, especially in postmenopausal women. The purpose of this study was to evaluate the effect of diabetes mellitus (DM), insulin, and TZDs on bone in postmenopausal Wistar rats. Methods: Sixteen postmenopausal Wistar rats were divided into four groups: (i) control group, (ii) Streptozotocin-induced DM group without treatment, (iii) Streptozotocin-induced DM group with insulin therapy, and (iv) Streptozotocin-induced DM group receiving rosiglitazone. Pictures of the obtained samples were taken under computer-equipped photo-light microscope, and bone tissue ratios were calculated in an area of 1 mm2. In this area, trabecular thicknesses were measured from six randomly selected regions. In addition, femoral neck regions were determined by measuring the farthest distance. Results: Compared to the control group, trabecular thicknesses were decreased in the uncontrolled DM and rosiglitazone groups. In the rosiglitazone-treated group, trabecular thickness was decreased compared to the uncontrolled DM group. The histological examination of the bones showed that uncontrolled DM and rosiglitazone treatment negatively affected the osteoblast and osteocyte activity. Insulin-treated group had a similar histologic examination compared to the control group. Conclusion: Our study showed that DM had unfavorable effects on bones, and rosiglitazone further exerts this effect. However, the negative effect of DM may be neutralized with the use of insulin. Keywords: diabetes mellitus, bone, osteoporosis, bone histomorphometry, rosiglitazone, insulin, thiazolidinediones

scholarly journals High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δAgonism

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Elisa Benetti ◽  
Raffaella Mastrocola ◽  
Mara Rogazzo ◽  
Fausto Chiazza ◽  
Manuela Aragno ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Gastrocnemius Muscle ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Intercellular Adhesion Molecule ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Intercellular Adhesion Molecule 1 ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome Proliferator Activated Receptor (PPAR)-δagonists may serve for treating metabolic diseases. However, the effects of PPAR-δagonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δagonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δupregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δactivation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.

Labyrinthectomy decreases bone mineral density in the femoral metaphysis in rats

2004 ◽  
Vol 14 (5) ◽  
pp. 361-365
Author(s):  
Régis Levasseur ◽  
Jean Pierre Sabatier ◽  
Olivier Etard ◽  
Pierre Denise ◽  
Annie Reber
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Weight Bearing ◽  
Whole Body ◽  
X Rays ◽  
Mineral Density ◽  
Femoral Metaphysis ◽  
Significant Difference ◽  
Distal Femoral Metaphysis ◽  
Vestibular Influence

To determine whether the vestibular system could influence bone remodeling in rats, we measured bone mineral density with dual energy X-rays absorptiometry before and 30 days after bilateral labyrinthectomy. Comparatively to intact control rats, labyrinthectomized animals showed a reduced bone mineral density in distal femoral metaphysis (p = 0.007): the variations between D0 and D30 were +3.0% for controls and -13.9% for labyrinthectomized rats. No significant difference between the 2 groups was observed in the whole body mineral density. These results suggest that the peripheral vestibular apparatus is a modulator of bone mass and more specifically in weight bearing bone. We discuss possible mechanisms of this vestibular influence probably mediated by the sympathetic nervous system.

The Effects of Signaling-Selective Parathyroid Hormone Analogs on Osteoporotic Osteocyte Apoptosis

2022 ◽  
Vol 12 (2) ◽  
pp. 316-322
Author(s):  
Meng-Sheng Song ◽  
Xiao Yu ◽  
Peng-Ze Rong ◽  
Qing-Jiang Pang
Keyword(s):  
Parathyroid Hormone ◽  
Immunohistochemical Staining ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Trabecular Thickness ◽  
Osteocyte Apoptosis ◽  
Trabecular Bone Microstructure ◽  
Hormone Analogs ◽  
Trabecular Number

Objectives: To compare the effects of signaling-selective parathyroid hormone analogs [G1, R19]hPTH(1–28) [GR(1–28)] and [G1, R19]hPTH(1–34) [GR(1–34)] on osteoporotic osteocyte apoptosis, and to explore the mechanism of the anti-osteoporotic difference. Methods: The osteoporosis model was established in eighty adult female C57BL/6 mice aged 12 weeks. The mice were subcutaneously administered with GR(1–28) and GR(1–34) 5 days per week for 8 weeks. Bilateral femur samples were collected at 4 and 8 weeks, and micro-computed tomography (CT), H&E staining and immunohistochemical staining analyses were performed. Results: From micro-CT analysis, GR(1–34) increased proximal femoral bone mineral density (BMD) and relative bone volume (BV/TV), which was higher than GR(1–28) did. In addition, more trabecular number (Tb.N), thinner trabecular thickness (Tb.Th) and wider trabecular separation (Tb.Sp) were measured at week 8 using GR(1–34). From H&E and immunohistochemical staining, a stronger apoptosis inhibition was induced by GR(1–34) with more Bcl-2 secretion but less Bax expression, as opposed to GR(1–28). Conclusions: GR(1–34) shows better anti-osteoporotic effects than GR(1–28), which appears to be attributed to the activation of the PLC-independent PKC signaling pathway triggered by the former, inhibiting osteocyte apoptosis through up-regulation of Bcl-2 and down-regulation of Bax to increase bone mass and improving trabecular bone microstructure to enhance bone quality by reducing trabecular number, increasing trabecular thickness and trabecular space.

scholarly journals The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 280 ◽  
Author(s):  
Anne-Marie Lundsgaard ◽  
Andreas M. Fritzen ◽  
Bente Kiens
Keyword(s):  
Skeletal Muscle ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Peroxisome Proliferator ◽  
Early Recovery ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Exercise ◽  
Exercise Induced

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

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