Peroxisome proliferator‐activated receptor <i>γ</i> activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes

Blanchard, Pierre‐Gilles; Turcotte, Véronique; Côté, Marie‐Pier; Gélinas, Yves; Nilsson, Solveig; Olivecrona, Gunilla; Deshaies, Yves; Festuccia, William T.

doi:10.1111/apha.12665

Cited by 29 publications

(22 citation statements)

References 57 publications

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“…Both RSG and oleic acid are PPARγ activators [ 40 ], thus, it is possible that activation of PPARγ may serve a protective role in PA-induced cell damage. As previously reported, PPARγ is also involved in the regulation of both CPT1s and DGATs [ 41 , 42 ]. Therefore, it follows that PPARγ may participate in the regulation of fatty acid metabolism, and activation of PPARγ may be an effective treatment for Sertoli cell dysfunction induced by saturated fatty acids.…”

Section: Discussionmentioning

confidence: 55%

Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells

Pan

Jing

et al. 2018

Reprod Biol Endocrinol

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The Sertoli cell is the only somatic cell within the seminiferous tubules, and is vital for testis development and spermatogenesis. Rosiglitazone (RSG) is a member of the thiazolidinedione family and is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. It has been reported that RSG protects various types of cells from fatty acid-induced damage. However, whether RSG serves a protective role in Sertoli cells against palmitic acid (PA)-induced toxicity remains to be elucidated. Therefore, the aim of the present study was to investigate the effect of RSG on PA-induced cytotoxicity in Sertoli cells. MTT assay and Oil Red O staining revealed that RSG ameliorated the PA-induced decrease in TM4 cell viability, which was accompanied by an alleviation of PA-induced lipid accumulation in cells. In primary mouse Sertoli cells, RSG also showed similar protective effects against PA-induced lipotoxicity. Knockdown of PPARγ verified that RSG exerted its protective role in TM4 cells through a PPARγ-dependent pathway. To evaluate the mechanism underlying the protective role of RSG on PA-induced lipotoxicity, the present study analyzed the effects of RSG on PA uptake, and the expression of genes associated with both fatty acid oxidation and triglyceride synthesis. The results demonstrated that although RSG did not affect the endocytosis of PA, it significantly elevated the expression of carnitine palmitoyltransferase (CPT)-1A, a key enzyme involved in fatty acid oxidation, which indicated that the protective effect of RSG may have an important role in fatty acid oxidation. On the other hand, the expression of CPT1B was not affected by RSG. Moreover, the expression levels of diacylglycerol O-acyltransferase (DGAT)-1 and DGAT2, both of which encode enzymes catalyzing the synthesis of triglycerides, were not suppressed by RSG. The results indicated that RSG reduced PA-induced lipid accumulation by promoting fatty acid oxidation mediated by CPT1A. The effect of RSG in protecting cells from lipotoxicity was also found to be specific to Sertoli cells and hepatocytes, and not to other cell types that do not store excess lipid in large quantities, such as human umbilical vein endothelial cells. These findings provide insights into the cytoprotective effects of RSG on Sertoli cells and suggest that PPARγ activation may be a useful therapeutic method for the treatment of Sertoli cell dysfunction caused by dyslipidemia.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0416-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 55%

Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells

Pan

Jing

et al. 2018

Reprod Biol Endocrinol

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“…AGPAT2 mutation can lead to congenital systemic adipotrophic diabetes (GCL), which is characterized by adipose tissue deficiency, insulin resistance, diabetes, and hyperlipidemia (Oswiecimska et al, 2019). AGPAT2 can also regulate adipose tissue by altering the activation of PI3K-AKT and PPARg (Blanchard et al, 2016), and the accumulation of triglycerides in adipocytes can be reduced by knocking AGPAT2 (Gale et al, 2006). Glycerol triphosphate dehydrogenase (GPD1) is a rate-limiting enzyme (Remize et al, 2001) that catalyzes the synthesis of glycerol, linking carbohydrate and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Silibinin on Protein Expression Profile in White Adipose Tissue of Obese Mice

et al. 2020

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Objective: To investigate the effect of silibinin on the protein expression profile of white adipose tissue (WAT) in obese mice by using Tandem Mass Tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: According to experimental requirements, 36 C57BL/6JC mice were randomly divided into normal diet group (WC group), high fat diet group (WF group), and high fat diet + silibinin group (WS group). WS group was intragastrically administered with 54 mg/ kg body weight of silibinin, and the WC group and the WF group were intragastrically administered with equal volume of normal saline. Serum samples were collected to detect fasting blood glucose and blood lipids. IPGTT was used to measure the blood glucose value at each time point and calculate the area under the glucose curve. TMT combined with LC-MS/MS were used to study the expression of WAT, and its cellular processes, biological processes, corresponding molecular functions, and related network molecular mechanisms were analyzed by bioinformatics. Finally, RT-PCR and LC-MS/MS were used to detect the mRNA and protein expressions of FABP5, Plin4, GPD1, and AGPAT2, respectively. Results: Although silibinin did not reduce the mice's weight, it did improve glucose metabolism. In addition, silibinin decreased the concentration of TC, TG, and LDL-C and increased the concentration of HDL-C in the serum of mice. In the WF/WS group, 182 differentially expressed proteins were up-regulated and 159 were down-regulated. While in the WS/WF group, 362 differentially expressed proteins were up-regulated and 176 were down-regulated. Further analysis found that these differential proteins are mainly distributed in the peroxisome proliferation-activated receptor (PPAR), lipolysis of fat cells, metabolism of glycerides, oxidative phosphorylation, and other signaling pathways, and participate in cell processes and lipid metabolism through catalysis and integration functions. Specifically, silibinin reduced the expression of several key factors such as FABP5, Plin4, GPD1, and AGPTA2.

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“…Thiazolidinediones (TZDs), also known as glitazones, are peroxisome proliferator-activated receptor (PPAR) agonists with numerous actions, spanning from glycemic and lipid control to inflammatory signaling and cell cycle mediation[ 44 ]. The phenomenon of glitazone treatment and subsequent increase in body weight that has been supported by the results of numerous studies appears to be tissue-specific, since the VAT depot of the subjects remains unaffected while there is a shift of excess energy storage towards the SCAT[ 45 - 47 ].…”

Section: Epicardial Fat and Antidiabetic Drugsmentioning

confidence: 99%

Effects of antidiabetic drugs on epicardial fat

Xourgia¹,

Papazafiropoulou²,

Μelidonis³

2018

WJD

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Epicardial adipose tissue is defined as a deposit of adipocytes with pathophysiological properties similar to those of visceral fat, located in the space between the myocardial muscle and the pericardial sac. When compared with subcutaneous adipose tissue, visceral adipocytes show higher metabolic activity, lipolysis rates, increased insulin resistance along with more steroid hormone receptors. The epicardial adipose tissue interacts with numerous cardiovascular pathways via vasocrine and paracrine signalling comprised of pro- and anti-inflammatory cytokines excretion. Both the physiological differences between the two tissue types, as well as the fact that fat distribution and phenotype, rather than quantity, affect cardiovascular function and metabolic processes, establish epicardial fat as a biomarker for cardiovascular and metabolic syndrome. Numerous studies have underlined an association of altered epicardial fat morphology, type 2 diabetes mellitus (T2DM) and adverse cardiovascular events. In this review, we explore the prospect of using the epicardial adipose tissue as a therapeutic target in T2DM and describe the underlying mechanisms by which the antidiabetic drugs affect the pathophysiological processes induced from adipose tissue accumulation and possibly allow for more favourable cardiovascular outcomes though epicardial fat manipulation.

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Peroxisome proliferator‐activated receptor γ activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes

Abstract: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.

Cited by 29 publications

References 57 publications

Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells

Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells

The Effect of Silibinin on Protein Expression Profile in White Adipose Tissue of Obese Mice

Effects of antidiabetic drugs on epicardial fat

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