Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice

Yang, Keum Jin; Noh, Jung‐Ran; Kim, Yong Hoon; Gang, Gil-Tae; Hwang, Jung Hwan; Yang, Suk Jin; Yeom, Young Il; Lee, Chul‐Ho

doi:10.1016/j.lfs.2010.08.002

Cited by 15 publications

(13 citation statements)

References 31 publications

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“…34;38;41 In our study, although not statistically significant, we found larger adipocytes after the PIO treatment, which are in line with several earlier reports. 38 …”

Section: Commentsupporting

confidence: 93%

“…Similar results have been shown in humans with type 2 diabetes who received PIO for 24 weeks, in mice fed a high-fat diet for 6 months and then treated with PIO for 2–3 months, and in db/db mice after 4-week of PIO treatment. 34;36–38 TZD therapy is associated with weight gain in some patients and in mouse models. 34;36;38;39 PIO treatment did not significantly increase total body weight in our mice.…”

Section: Commentmentioning

confidence: 99%

“…34;36–38 TZD therapy is associated with weight gain in some patients and in mouse models. 34;36;38;39 PIO treatment did not significantly increase total body weight in our mice. On the contrary, the PIO group gained less weight than the CTR animals.…”

Section: Commentmentioning

confidence: 99%

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Pioglitazone therapy in mouse offspring exposed to maternal obesity

Kalanderian

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Patrikeev

et al. 2013

American Journal of Obstetrics and Gynecology

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Objective Pioglitazone (PIO), an antidiabetic drug of the thiazolidinedione family, improves glucose and lipid metabolism in muscle, adipose, and liver tissues via peroxisome proliferator-activated receptor gamma (PPARγ) activation. We hypothesize that PIO therapy will improve the metabolic status of offspring exposed to maternal obesity in a mouse model developmentally programmed for metabolic syndrome (MetS). Study Design CD-1 female mice were fed a high-fat diet for 3 months prior to breeding and throughout pregnancy and lactation. The pups were weaned to a standard-fat diet. Offspring were randomly assigned to receive 40 mg/kg of PIO in 0.5% of methyl cellulose or 0.5% methyl cellulose by daily oral gavage for 2 weeks. The pre- and post-treatment total body weights of the pups were recorded. Visceral (VAT) and subcutaneous (SAT) adipose tissue were evaluated using micro-computed tomography. Serum analytes were measured. Post-treatment, minimally invasive microendoscopic fluorescence confocal imaging and intraperitoneal glucose tolerance tests were performed. The data were analyzed using appropriate statistical tests (significance, P<0.05). Results PIO therapy resulted in lower total body weight and lower VAT gain, and increased SAT. PIO significantly lowered triglyceride, insulin levels, and HOMA-IR in males, and fasting glucose in females. There was a trend toward larger adipocyte size. Conclusion Short-term PIO therapy in the offspring of obese mothers attenuates metabolic changes associated with the developmental programming of metabolic syndrome. These novel data suggest a potential role for drugs that activate PPARγ receptors to prevent MetS in the adult offspring at risk to develop metabolic alterations.

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“…34;38;41 In our study, although not statistically significant, we found larger adipocytes after the PIO treatment, which are in line with several earlier reports. 38 …”

Section: Commentsupporting

confidence: 93%

Section: Commentmentioning

confidence: 99%

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Pioglitazone therapy in mouse offspring exposed to maternal obesity

Kalanderian

Abate

Patrikeev

et al. 2013

American Journal of Obstetrics and Gynecology

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“…Moreover, also in agreement with the differential effects of pioglitazone and rosiglitazone on plasma lipids and lipoprotein observed in humans (see above), animal studies suggest some differences between pioglitazone and rosiglitazone in their effects on lipid metabolism. Thus, in white adipose tissue of db/db mice, rosiglitazone induced mitochondrial β-oxidation more strongly than pioglitazone [19], while de novo lipogenesis in mouse liver was preferentially stimulated by rosiglitazone [20]–[22]. In skeletal muscle, somehow conflicting results concerning modulation of β-oxidation by pioglitazone and rosiglitazone were found [23], [24].…”

Section: Introductionmentioning

confidence: 99%

Unmasking Differential Effects of Rosiglitazone and Pioglitazone in the Combination Treatment with n-3 Fatty Acids in Mice Fed a High-Fat Diet

et al. 2011

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Combining pharmacological treatments and life style interventions is necessary for effective therapy of major diseases associated with obesity, which are clustered in the metabolic syndrome. Acting via multiple mechanisms, combination treatments may reduce dose requirements and, therefore, lower the risk of adverse side effects, which are usually associated with long-term pharmacological interventions. Our previous study in mice fed high-fat diet indicated additivity in preservation of insulin sensitivity and in amelioration of major metabolic syndrome phenotypes by the combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and rosiglitazone, i.e. an anti-diabetic drug of the thiazolidinedione (TZD) family. We investigated here whether pioglitazone, a TZD-drug in clinical use, could elicit the additive beneficial effects when combined with n-3 LC-PUFA. Adult male mice (C57BL/6N) were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; (iii) cHF+F+ROSI; (iv) cHF+PIO, cHF with 50 mg pioglitazone/kg diet; and (v) cHF+F+PIO, or chow-fed. Plasma concentrations of 163 metabolites were evaluated using a targeted metabolomics approach. Both TZDs preserved glucose homeostasis and normal plasma lipid levels while inducing adiponectin, with pioglitazone showing better effectiveness. The beneficial effects of TZDs were further augmented by the combination treatments. cHF+F+ROSI but not cHF+F+PIO counteracted development of obesity, in correlation with inducibility of fatty acid β-oxidation, as revealed by the metabolomic analysis. By contrast, only cHF+F+PIO eliminated hepatic steatosis and this treatment also reversed insulin resistance in dietary obese mice. Our results reveal differential effects of rosiglitazone and pioglitazone, unmasked in the combination treatment with n-3 LC-PUFA, and support the notion that n-3 LC-PUFA could be used as add-on treatment to TZDs in order to improve diabetic patient's therapy.

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“…In addition, primary products of lipid oxidation, but not secondary products, have been shown to act as ligands of PPARγ [11]. Activation of PPARγ promotes modest increases in fat mass as seen in mice [12] and humans [13] treated with rosiglitazone, a known PPARγ agonist. We hypothesized that the increase in fat pad mass among mice consuming HSO could be due to an upregulation of PPARγ.…”

Section: Discussionmentioning

confidence: 99%

A diet containing soybean oil heated for three hours increases adipose tissue weight but decreases body weight in C57BL/6 J mice

et al. 2013

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BackgroundOur previous work showed that dietary oxidized linoleic acid given, as a single fatty acid, to LDL receptor knockout mice decreased weight gain as compared to control mice. Other studies have also reported that animals fed oils heated for 24 h or greater showed reduced weight gain. These observations, while important, have limited significance since fried foods in the typical human diet do not contain the extreme levels of oxidized lipids used in these studies. The main goal of this study was to investigate the effects of a diet containing soybean oil heated for 3 h on weight gain and fat pad mass in mice. Additionally, because PPARγ and UCP-1 mediate adipocyte differentiation and thermogenesis, respectively, the effect of this diet on these proteins was also examined.FindingsFour to six week old male C57BL/6 J mice were randomly divided into three groups and given either a low fat diet with heated soybean oil (HSO) or unheated soybean oil (USO) or pair fed for 16 weeks. Weight and food intake were monitored and fat pads were harvested upon the study’s termination. Mice consuming the HSO diet had significantly increased fat pad mass but gained less weight as compared to mice in the USO group despite a similar caloric intake and similar levels of PPARγ and UCP1.ConclusionThis is the first study to show that a diet containing soybean oil heated for a short time increases fat mass despite a decreased weight gain in C57BL/6 J mice. The subsequent metabolic consequences of this increased fat mass merits further investigation.

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Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice

Cited by 15 publications

References 31 publications

Pioglitazone therapy in mouse offspring exposed to maternal obesity

Pioglitazone therapy in mouse offspring exposed to maternal obesity

Unmasking Differential Effects of Rosiglitazone and Pioglitazone in the Combination Treatment with n-3 Fatty Acids in Mice Fed a High-Fat Diet

A diet containing soybean oil heated for three hours increases adipose tissue weight but decreases body weight in C57BL/6 J mice

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