Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo

Bogacka, Iwona; Xie, Hui; Bray, George A.; Smith, Steven R.

doi:10.2337/diabetes.54.5.1392

Cited by 428 publications

(389 citation statements)

References 52 publications

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“…When the db/db mice were treated with the thiazolidinedione (TZD)-derivative rosiglitazone, mitochondrial morphology and levels of respiratory chain proteins were restored in adipocytes, fatty acid oxidation was improved, and hyperglycaemia was reduced. These data are in line with recent studies by Bogacka et al and Wilson-Fritch et al, which showed that TZDs induce mitochondrial biogenesis, both in human and mouse adipocytes, with concomitant upregulation of genes involved in fatty acid beta-oxidation [11,12].…”

supporting

confidence: 92%

“…Although these studies suggest a direct role for mitochondria [10][11][12], they do not exclude the alternative possibility that TZD-induced improvements in mitochondrial function in adipocytes are an indirect consequence of improved glycaemic control, which was also a feature of these studies. Hyperglycaemia may itself switch cellular metabolism to a glycolytic state, leading to the reduced expression of mitochondrial genes, as observed, for example, in the study of insulin-regulated vs diabetesregulated gene expression in MIRKO mice [13].…”

mentioning

confidence: 80%

“…The recent discovery of adipokines has placed adipocytes back in the centre of the metabolic stage. The recent publications by Choo et al, Bogacka et al and Wilson-Fritsch et al [10][11][12] have introduced another exciting possibility into adipocyte research: that mitochondria in adipocytes may shield against the development of type 2 diabetes.…”

mentioning

confidence: 99%

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Mitochondrial dysfunction in adipocytes: the culprit in type 2 diabetes?

Maassen

2006

Diabetologia

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supporting

confidence: 92%

mentioning

confidence: 80%

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Mitochondrial dysfunction in adipocytes: the culprit in type 2 diabetes?

Maassen

2006

Diabetologia

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“…Since LA and ALC are nutrients without apparent side effects, they might exert better PPARg/a ligand stimulation than glucose-lowering agents or other ligands. The Pparg agonist pioglitazone and Ppara agonist WY-14,643 were able to increase Ppargc1a expression and mtDNA copy number, as well as enhancing the oxidative capacity of white adipose tissue leading to insulin sensitisation [12,13,37].…”

Section: Discussionmentioning

confidence: 99%

R-α-Lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes

et al. 2007

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Aims/hypothesis The aim of the study was to address the importance of mitochondrial function in insulin resistance and type 2 diabetes, and also to identify effective agents for ameliorating insulin resistance in type 2 diabetes. We examined the effect of two mitochondrial nutrients, R-α-lipoic acid (LA) and acetyl-L-carnitine (ALC), as well as their combined effect, on mitochondrial biogenesis in 3T3-L1 adipocytes. Methods Mitochondrial mass and oxygen consumption were determined in 3T3-L1 adipocytes cultured in the presence of LA and/or ALC for 24 h. Mitochondrial DNA and mRNA from peroxisome proliferator-activated receptor gamma and alpha (Pparg and Ppara) and carnitine palmitoyl transferase 1a (Cpt1a), as well as several transcription factors involved in mitochondrial biogenesis, were evaluated by real-time PCR or electrophoretic mobility shift (EMSA) assay. Mitochondrial complexes proteins were measured by western blot and fatty acid oxidation was measured by quantifying CO 2 production from [1-14 C] palmitate. Results Treatments with the combination of LA and ALC at concentrations of 0.1, 1 and 10 μmol/l for 24 h significantly increased mitochondrial mass, expression of mitochondrial DNA, mitochondrial complexes, oxygen consumption and fatty acid oxidation in 3T3L1 adipocytes. These changes were accompanied by an increase in expression of Pparg, Ppara and Cpt1a mRNA, as well as increased expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha (Ppargc1a), mitochondrial transcription factor A (Tfam) and nuclear respiratory factors 1 and 2 (Nrf1 and Nrf2). However, the treatments with LA or ALC alone at the same concentrations showed little effect on mitochondrial function and biogenesis. Conclusions/interpretation We conclude that the combination of LA and ALC may act as PPARG/A dual ligands to complementarily promote mitochondrial synthesis and adipocyte metabolism.

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“…55 There are indications of impaired expression of marker genes of the brown adipocyte phenotype in adipose tissue from adult humans with insulin resistance, 56 and several reports have indicated that treatment of rodents or humans with the insulin-sensitizing thiazolidinedione drugs favors the acquisition by white adipose tissue of 'brown fat-like' features. 25,[57][58][59] Until recently, the re-appearance of substantial amounts of brown adipocytes in adult humans had been reported only in adipose tissue surrounding pheochromocytomas 54 but recent data obtained from positron emission tomography analysis has led to the unexpected finding of substantial amounts of active brown fat in some anatomical sites of adult humans including the neck region. 60 Thus, regardless of the precise mechanisms eliciting the appearance of 'buffalo humps' in HALS patients, this phenomenon confirms that in adult humans there is a pool of cells in adipose depots capable of proliferation and differentiation into an adipocyte phenotype that includes brown fat-like features.…”

Section: Lipomatosis In Hals Reveals a Potential For Brown Adipocyte mentioning

confidence: 99%