Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

Lee, Y. H.; Nair, Saraswathy; Rousseau, Elodie; Allison, David B.; Page, Grier P.; Tataranni, P. Antonio; Bogardus, Clifton; Permana, Paska A.

doi:10.1007/s00125-005-1867-3

Cited by 230 publications

(233 citation statements)

References 40 publications

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“…13 In addition, an upregulation of NOX4 in the adipose tissue of obese Pima Indians compared with lean subjects was detected. 44 Our study confirmed upregulation of adipose tissue NOX4 expression upon HFD feeding (Supplementary Figure S5). However, in view of the results of our current study NOX4 upregulation should be regarded as a defensive mechanism to limit adipose tissue expansion.…”

Section: Discussionsupporting

confidence: 80%

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

Mouche

Sajic

et al. 2012

Int J Obes

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OBJECTIVE: NADPH oxidase 4 (NOX4) is a reactive oxygen species (ROS) producing NADPH oxidase that regulates redox homeostasis in diverse insulin-sensitive cell types. In particular, NOX4-derived ROS is a key modulator of adipocyte differentiation and mediates insulin receptor signaling in mature adipocytes in vitro. Our study was aimed at investigating the role of NOX4 in adipose tissue differentiation, whole body metabolic homeostasis and insulin sensitivity in vivo. DESIGN: Mice with genetic ablation of NOX4 (NOX4-deficient mice) were subjected to chow or high-fat-containing diet for 12 weeks. Body weight gain, adiposity, insulin sensitivity, and adipose tissue and liver gene and protein expression were analyzed and compared with similarly treated wild-type mice. RESULTS: Here, we report that NOX4-deficient mice display latent adipose tissue accumulation and are susceptible to diet-induced obesity and early onset insulin resistance. Obesity results from accelerated adipocyte differentiation and hypertrophy, and an increase in whole body energy efficiency. Insulin resistance is associated with increased adipose tissue hypoxia, inflammation and adipocyte apoptosis. In the liver, more severe diet-induced steatosis was observed due to the lack of proper upregulation of mitochondrial fatty acid b-oxidation. CONCLUSION: These findings identify NOX4 as a regulator of metabolic homeostasis. Moreover, they indicate an anti-adipogenic role for NOX4 in vivo and reveal its function as a protector against the development of diet-induced obesity, insulin resistance and hepatosteatosis.

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Section: Discussionsupporting

confidence: 80%

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

Mouche

Sajic

et al. 2012

Int J Obes

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“…Subjects for adipose tissue biopsies were admitted as inpatients to our Clinical Research Center, and, after an overnight fast, underwent a subcutaneous abdominal needle biopsy under local anesthesia with 1% lidocaine. Collagenase digestion of the subcutaneous abdominal adipose tissue biopsy samples was performed as previously described (13,14). Briefly, the preadipocyte-containing infranatant was collected into a separate tube and washed several times with Hanks' balanced salt solution.…”

Section: Methodsmentioning

confidence: 99%

Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians

et al. 2006

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Prior microarray studies comparing global gene expression patterns in preadipocytes/stromal vascular cells isolated from nonobese nondiabetic versus obese nondiabetic Pima Indians showed that matrix metalloproteinase 9 (MMP9) is upregulated in obese subjects. The current study targeted analysis of nine additional MMP genes that cluster to a region on chromosome 11q22 that is linked to BMI and percent body fat. Differential-display PCR showed that MMP3 is downregulated in preadipocytes/stromal vascular cells from obese subjects, and real-time PCR showed that MMP3 expression levels are negatively correlated with percent body fat. To determine whether variants within MMP3 are responsible for its altered expression, MMP3 was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses. Two variants were associated with both BMI and type 2 diabetes, and two additional variants were associated with type 2 diabetes alone; however, none of these variants were associated with MMP3 expression levels. We propose that the MMP3 pathway is altered in human obesity, but this alteration may be the result of a combination of genetic variation within the MMP3 locus itself, as well as variation in additional factors, either primary or secondary to obesity, that regulate expression of the MMP3 gene. Diabetes 55: 3160 -3165, 2006

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“…[15][16][17][18] Weight reduction induces changes in the expression of various genes in AT. [19][20][21][22][23] A few studies have applied microarray technologies to study gene expression in AT of massively obese subjects either in comparison to lean subjects cross-sectionally 24,25 or after short-term weight reduction. 26,27 These studies have demonstrated downregulation in the expression of genes involved in inflammation and desaturation of fatty acids.…”

Section: Introductionmentioning

confidence: 99%

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study

et al. 2007

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Objective: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the longterm moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. Design: Randomized controlled and individualized weight reduction intervention. Subjects: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 6077 years were randomized either to a weight reduction (WR) (n ¼ 28) or a control (n ¼ 18) group lasting for 33 weeks. Measurements: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction X5%, n ¼ 9) and control group (n ¼ 10). The results were confirmed using quantitative PCR. Results: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S I and the change in body weight was found (r ¼ À0.44, P ¼ 0.026). Downregulation of gene expression (Po0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (À39716%, Po0.0001). Moreover, its expression correlated with insulin sensitivity (r ¼ À0.34, P ¼ 0.005) before the intervention and with body adiposity both before (r ¼ 0.42, P ¼ 0.007) and after (r ¼ 0.30, P ¼ 0.056) the intervention. Conclusion: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

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Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

Cited by 230 publications

References 40 publications

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study

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