Pioglitazone Treatment Enlarges Subcutaneous Adipocytes in Insulin-Resistant Patients

Koenen, Tim B.; Tack, Cees J.; Kroese, Jeanne Margot; Hermus, A.R.M.M.; Sweep, Fred C.G.J.; Laak, Jeroen van der; Stalenhoef, Anton F. H.; Graaf, Jacqueline de; Tits, L.J.H. van; Stienstra, Rinke

doi:10.1210/jc.2009-0517

Cited by 37 publications

(32 citation statements)

References 23 publications

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“…Contrast between TZD treatment and weight loss TZD treatment increases the size of the large adipose cells, at least according to this study and that of Koenen et al 25 Weight loss, which also improves insulin sensitivity, in contrast decreases the size of the large adipose cells. 32 Here, the fall in glucose was nearly a mirror image of the rise in the size of the large adipose cells (compare Fig.…”

Section: Discussionsupporting

confidence: 72%

“…Koenen et al 25 reported that the pioglitazone treatment significantly improved insulin sensitivity in T2D patients, and that this was accompanied by a significant enlargement of the subcutaneous adipose cell size and increases of mRNA expression levels of adiponectin and GLUT4 in adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 Early studies showed that TZD treatment ameliorates insulin resistance, which is associated with increased numbers of small adipose cells in adipose tissue both in animal models [17][18][19][20] and in human T2D subjects. 21,22 However, other studies showed that TZD treatment did not change 23,24 or even increased 25 adipose cell size despite increased insulin sensitivity in those treated T2D patients. In order to improve our power to observe changes, we for the first time studied the effects of a TZD longitudinally, with assessments at multiple time points over the course of 90 d. We obtained biopsies of subcutaneous adipose tissue and assessed them for cell size distributions and expression of key adipose genes along with blood samples to track ancillary metabolic parameters.…”

Section: Introductionmentioning

confidence: 96%

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Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

et al. 2014

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Early studies reported that the size of adipose cells positively correlates with insulin resistance, but recent evidence suggests that the relationship between adipose cell size and insulin resistance is more complex. We previously reported that among BMI-matched moderately obese subjects who were either insulin sensitive or resistant insulin resistance correlated with the proportion of small adipose cells, rather than the size of the large adipose cells, whereas the size of large adipose cells was found to be a predictor of insulin resistance in the first-degree relatives of type 2 diabetic (T2D) patients. The relationship between adipose cellularity and insulin resistance thus appears to depend on the metabolic state of the individual. We did a longitudinal study with T2D patients treated with the insulin-sensitizer rosiglitazone to test the hypothesis that improved insulin sensitivity is associated with increased adipocyte size. Eleven T2D patients were recruited and treated with rosiglitazone for 90 days. Blood samples and needle biopsies of abdominal subcutaneous fat were taken at six time points and analyzed for cell size distributions. Rosiglitazone treatment ameliorated insulin resistance as evidenced by significantly decreased fasting plasma glucose and increased index of insulin sensitivity, QUICKI. In association with this, we found significantly increased size of the large adipose cells and, with a weaker effect, increased proportion of small adipose cells. We conclude rosiglitazone treatment both enlarges existing large adipose cells and recruits new small adipose cells in T2D patients, improving fat storage capacity in adipose tissue and thus systemic insulin sensitivity.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

et al. 2014

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“…Thus, adipogenesis probably has a role in the pathology of obesity in human adults. However, there are significant differences in lipid and glucose metabolism between adipocyte hypertrophy and hyperplasia (9)(10)(11). Recent studies have shown that adipocyte hypertrophy is negatively correlated with dyslipidemia and insulin resistance, independent of body composition (9,11).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown that adipocyte hypertrophy is negatively correlated with dyslipidemia and insulin resistance, independent of body composition (9,11). Notably, hyperplasia, which is characterized by an increased number of small subcutaneous adipocytes, may have a positive effect on lipid metabolism and insulin sensitivity through preadipocyte differentiation (9,10). Therefore, improving the characteristics of adipocytes may have therapeutic potential for treating obesity and insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Yang

Ren

Song

et al. 2013

International Journal of Molecular Medicine

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Abstract. Glucagon-like peptide 1 (GLP-1), a gut-derived peptide, has been reported to have profound effects on metabolism and to reduce insulin resistance. Adipocyte hyperplasia stimulated by preadipocyte differentiation has a positive effect on adipose tissue insulin sensitivity. However, it remains less clear whether GLP-1 plays a role in adipogenesis. In this study, we examined the effect of GLP-1 on preadipocyte differentiation and investigated the mechanisms that may be involved in this effect. In our 3T3-L1 cell study, we tested the levels of adipocyte-specific markers and signaling pathways during preadipocyte differentiation. In addition, Oil Red O staining was used to examine lipid accumulation. Image Pro Plus 5.02 was used to analyze the size and number of lipid droplets. We found that GLP-1 elevated the protein expression levels of free fatty acid-binding protein 4 (aP2) and the transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) in a dose-dependent manner during 3T3-L1 preadipocyte differentiation. Furthermore, RT-PCR results showed that GLP-1 promoted CCAAT/enhancer-binding protein α (C/EBPα) and lipoprotein lipase (LPL) expression at the transcriptional level. These data suggest that GLP-1 promotes preadipocyte differentiation. Our study also found that treatment of the cells with 100 nM GLP-1 enhanced the phosphorylation of Akt signaling during the first 24 h of differentiation. Although Oil Red O staining showed that GLP-1 had no significant effect on lipid accumulation, there were increased numbers of small adipocytes in the cells treated with 100 nM GLP-1. Taken together, these results indicate that GLP-1 regulates 3T3-L1 adipogenesis and the Akt signaling pathway may be involved in this process. The differentiated small adipocytes may have a positive effect against insulin resistance and obesity. IntroductionThe growing prevalence of obesity constitutes a major health problem worldwide (1). Obesity, particularly abdominal obesity, has a strong relationship with insulin resistance and is a major risk factor for type 2 diabetes and cardiovascular disease (2,3). The imbalance between energy intake and expenditure contributes to the development of obesity (1,4); the cellular mechanisms for which include the expansion of white adipose tissue via the hypertrophy of preexisting adipocytes and hyperplasia resulting from the adipogenesis of preadipocytes (4,5). When animals are maintained on a highfat diet, adipo cyte cell size initially increases, followed by an increase in fat cell number upon prolonged over-nutrition (6). In adults, ~10% of fat cells are renewed from preadipocytes annually (7). One study in adults demonstrated that short-term overfeeding increases the adipocyte cell numbers (8). Thus, adipogenesis probably has a role in the pathology of obesity in human adults. However, there are significant differences in lipid and glucose metabolism between adipocyte hypertrophy and hyperplasia (9-11). Recent studies have shown that adipocyte hypertrophy is negatively corre...

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Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia

Stępień

Krishan

2020

Cochrane Database of Systematic Reviews

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Pioglitazone Treatment Enlarges Subcutaneous Adipocytes in Insulin-Resistant Patients

Abstract: In the human situation, treatment of insulin-resistant subjects with pioglitazone improves insulin sensitivity, whereas at the same time, sc adipocyte cell surface increases.

Cited by 37 publications

References 23 publications

Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia

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