Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance

Johansson, Lars-Åke; Danielsson, Anders; Parikh, Hemang; Klintenberg, Maria; Norström, Fredrik; Groop, Leif; Ridderstråle, Martin

doi:10.4016/48515.01

Cited by 14 publications

(20 citation statements)

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“…These data are in line with the fi nding that ABCG1 is one of the most upregulated genes in human adipose tissue samples after weight loss ( 30 ). ABCG1 is a member of the ABC superfamily of transmembrane transporters that facilitate the transport of diverse substrates across membranes ( 31,32 ).…”

Section: Methodssupporting

confidence: 69%

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ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction

Tarling

McMillen

et al. 2015

Journal of Lipid Research

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Supplemental Material can be found at: 2338 Journal of Lipid Research Volume 56, 2015ATMs and that Abcg1 plays a key role in modulating ATM cholesterol levels in obesity and acute weight loss.ATMs were collected from mice for which the myeloid cells had been replaced by bone marrow transplantation (BMT) from Abcg1 Ϫ / Ϫ mice and from WT mice undergoing autologous BMT. We found that Abcg1 expression affected the steady-state cholesterol levels of ATMs, with Abcg1ATMs having the highest total cholesterol content. Other sterol species were not evaluated due to limitations in ATM cell quantities. We found that the ratio of M1 to M2 ATMs was altered with loss of Abcg1 expression, and that Abcg1 was most highly expressed by M2 rather than proinfl ammatory M1 macrophages suggesting that M2 cells have a unique role in adipose tissue sterol homeostasis. Overall, this study identifi es ABCG1 as an important protein determining the relative levels of ATMs and cholesterol metabolism especially in M2 macrophages. Understanding the contribution of ABCG1 to ATM cholesterol homeostasis may provide new information for controlling obesity, weight loss, and related disorders such as lung, liver, and gallbladder diseases ( 38-40 ). MATERIALS AND METHODS MiceIsogenic WT C57BL/6 mice were purchased from the Jackson Laboratory (Bar Harbor, ME; #000664). ABCG1 knockout ( Abcg1 Ϫ / Ϫ ) mice on a C57BL/6 background were generated as previously described ( 41 ). BMT was conducted using C57BL/6 male mice as acceptors of either C57BL/6 bone marrow cells (WT-BMT) or cells from Abcg1 Ϫ / Ϫ mice ( Abcg1 Ϫ / Ϫ BMT) using procedures as described below. Femurs taken from Abcg1Ϫ / Ϫ mice were placed in PBS and sent overnight on ice from the University of California, Los Angeles to the University of Washington where bone marrow cells were isolated. In addition, C57BL/6 male mice raised at the University of Washington (three to four generations from the Jackson Laboratory) were used as a reference strain for measures of body composition. All mice were housed in pathogen-free conditions, in a temperature-and humidity-controlled environment (12 h light/dark cycle). Animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee of University of Washington. Study designBMT was performed essentially as described ( 42 ). Briefl y, male C57BL/6 mice (WT) at 13 weeks of age were irradiated (950 rads) and then engrafted with either WT or Abcg1 Ϫ / Ϫ bone marrow cells (5 × 10 6 cells/mouse; n = 20 in each group) by retroorbital injection. Mice were maintained on pelleted rodent chow (LabDiet 5053; Purina Mills, St. Louis, MO) and acidifi ed water with neomycin (X-gen Pharmaceuticals, Big Flats, NY) for 4 weeks of recovery. Mice were then fed a high-fat diet (HFD) [D12492; Research Diets Inc., New Brunswick, NJ; 60% kcal (primarily lard) and 20% kcal carbohydrate (maltodextrin 10 and sucrose)] for 13 weeks. Mice were then randomly assigned to one of two groups for another 3 weeks of either continued ad libitum HFD feeding or to...

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Section: Methodssupporting

confidence: 69%

“…Abcg1 is highly expressed in ATMs of obese mice ( 17 ) and adipose tissue in humans ( 30 ). To determine whether ATM cholesterol levels are controlled in part by ABCG1, we compared cellular cholesterol levels and chemical composition between WT-BMT and Abcg1…”

Section: Abcg1 Genotype Determines Cholesterol Content Of Atms In Obementioning

confidence: 99%

ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction

Tarling

McMillen

et al. 2015

Journal of Lipid Research

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“…35 Collagen COL3A1 expression is higher after weight loss 34 and its turnover is regulated by the metalloprotease MMP9 in human adipose tissue. 35 MMP9 itself is involved in ECM remodeling, with increased expression during adipogenesis, 36 its expression is reduced after weight loss 37 and increased in obese stroma-vascular fraction 38 and in adipose tissue with obesity-associated insulin resistance. 39 Aquaporin AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to triglyceride accumulation in adipose tissue, and adult onset obesity 40 ; its expression is down regulated in obese adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis

et al. 2015

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Obesity is linked to adipose tissue hypertrophy (increased adipocyte cell size) and hyperplasia (increased cell number). Comparative analyses of gene datasets allowed us to identify 1426 genes which may represent common adipose phenotype in humans and mice. Among them we identified several adipocyte-specific genes dysregulated in obese adipose tissue, involved in either fatty acid storage (acyl CoA synthase ACSL1, hormone-sensitive lipase LIPE, aquaporin 7 AQP7, perilipin PLIN) or cell adhesion (fibronectin FN1, collagens COL1A1, COL1A3, metalloprotein MMP9, or both (scavenger receptor FAT/CD36). Using real-time analysis of cell surface occupancy on xCELLigence system we developed a new method to study lipid uptake and differentiation of mouse 3T3L1 fibroblasts and human adipose stem cells. Both processes are regulated by insulin and fatty acids such as oleic acid. We showed that fatty acid addition to culture media increased the differentiation rate and was required for full differentiation into unilocular adipocytes. Significant activation of lipogenesis, i.e. lipid accumulation, by either insulin or oleic acid was monitored in times ranging from 1 to 24 h, depending on differentiation state, whereas significant effects on adipogenesis, i.e., surperimposed lipid accumulation and gene transcriptional regulations were measured after 3 to 4 d. Combination of selected times for analysis of lipid contents, cell counts, size fractionations, and gene transcriptional regulations showed that FAT/CD36 specific inhibitor AP5258 significantly increased cell survival of oleic acid-treated mouse and human adipocytes, and partially restored the transcriptional response to oleic acid in the presence of insulin through JNK pathway. Taken together, these data open new perspectives to study the molecular mechanisms commonly dysregulated in mouse and human obesity at the level of lipogenesis linked to hypertrophy and adipogenesis linked to hyperplasia

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“…Indeed, gene expression analysis of subcutaneous AT from obese patients following caloric restriction [11][12][13][14] or surgery 15 did not reveal any reduction of ABCG1 expression in AT after weight loss but instead detected an upregulation of this pathway in some cases. 16,17 These intriguing data suggest that ABCG1 can exert a more complex role in AT than that recently identified by us in adipocytes. 3 Thus, Edgel et al reported that although Abcg1 expression was increased in AT of db/db mice during obesity, an elevation of Abcg1 expression was equally observed in those mice after caloric restriction.…”

mentioning

confidence: 62%

Adipose ABCG1: A potential therapeutic target in obesity?

Frisdal

Goff

2015

Adipocyte

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Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance

Cited by 14 publications

References 0 publications

ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction

ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction

Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis

Adipose ABCG1: A potential therapeutic target in obesity?

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