RGC-32 Deficiency Protects against Hepatic Steatosis by Reducing Lipogenesis

Cui, Xiaojie; Luan, Jun-Na; Chen, Shiyou

doi:10.1074/jbc.m114.630186

Cited by 22 publications

(19 citation statements)

References 53 publications

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“…Food intake and voluntary physical activity were measured at 12 weeks of age and fasting energy expenditure was measured at 6 and 12 weeks of age as previously described (Cui et al 2015, Fam et al 2015. Briefly, food intake was determined in mice that were housed separately by weighing food each morning over a seven-day period and daily food intake averaged over the seven days.…”

Section: Metabolic Analysesmentioning

confidence: 99%

“…Briefly, food intake was determined in mice that were housed separately by weighing food each morning over a seven-day period and daily food intake averaged over the seven days. Voluntary activity was measured by monitoring the use of running wheels with a computerised metre (Fam et al 2015) and fasting energy expenditure was determined by measuring the body weight of the mice prior to and following an overnight fast of 16 h and calculated as the change in body weight (Cui et al 2015).…”

Section: Metabolic Analysesmentioning

confidence: 99%

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The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

Russell

Mangiafico

Fam

et al. 2018

Journal of Endocrinology

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It is well established that testosterone negatively regulates fat mass in humans and mice; however, the mechanism by which testosterone exerts these effects is poorly understood. We and others have shown that deletion of the androgen receptor (AR) in male mice results in a phenotype that mimics the three key clinical aspects of hypogonadism in human males; increased fat mass and decreased bone and muscle mass. We now show that replacement of the gene specifically in mesenchymal progenitor cells (PCs) residing in the bone marrow of Global-ARKO mice, in the absence of the AR in all other tissues (PC-AR Gene Replacements), completely attenuates their increased fat accumulation. Inguinal subcutaneous white adipose tissue and intra-abdominal retroperitoneal visceral adipose tissue depots in PC-AR Gene Replacement mice were 50-80% lower than wild-type (WT) and 75-90% lower than Global-ARKO controls at 12 weeks of age. The marked decrease in subcutaneous and visceral fat mass in PC-AR Gene Replacements was associated with an increase in the number of small adipocytes and a healthier metabolic profile compared to WT controls, characterised by normal serum leptin and elevated serum adiponectin levels. Euglycaemic/hyperinsulinaemic clamp studies reveal that the PC-AR Gene Replacement mice have improved whole-body insulin sensitivity with higher glucose infusion rates compared to WT mice and increased glucose uptake into subcutaneous and intra-abdominal fat. In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function.

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Section: Metabolic Analysesmentioning

confidence: 99%

Section: Metabolic Analysesmentioning

confidence: 99%

The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

Russell

Mangiafico

Fam

et al. 2018

Journal of Endocrinology

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“…Total RNA was extracted from cells or tissues with Trizol Reagent (15596018; Thermo Fisher Scientific, Waltham, MA, USA), according to the manufacturer's instructions and as described previously (28). RNA was treated with RNase-free DNase 1 (M0303S; New England Biolabs, Ipswich, MA, USA) to remove contaminating genomic DNA.…”

Section: Rna Extraction and Sequencing And Real-time Quantitative Rt-mentioning

confidence: 99%

Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting ß3‐adrenergic receptor/mTORC1 signaling

et al. 2018

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Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be determined. In the present study, RGC-32 expression in white adipose tissue (WAT) was suppressed during cold exposure-induced WAT browning. Rgc32 significantly increased thermogenic gene expression in the differentiated stromal vascular fraction (SVF) of inguinal (i)WAT and interscapular brown adipose tissue (BAT). Rgc32 and cold exposure regulated a common set of genes in iWAT, as shown by RNA sequencing data. Pathway enrichment analyses showed that Rgc32 down-regulated PI3K/Akt signaling-related genes. Akt phosphorylation was also consistently decreased in Rgc32 iWAT, which led to an increase in β3-adrenergic receptor (β3-AR) expression and subsequent activation of mammalian target of rapamycin complex (mTORC)-1. β3-AR antagonist SR 59230A and mTORC1 inhibitor rapamycin blocked Rgc32-induced thermogenic gene expression in both iWAT and interscapular BAT. These results indicate that RGC-32 suppresses adipose tissue thermogenic gene expression through down-regulation of β3-AR expression and mTORC1 activity via a PI3K/Akt-dependent mechanism.-Chen, S., Mei, X., Yin, A., Yin, H., Cui, X.-B., Chen, S.-Y. Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting β3-adrenergic receptor/mTORC1 signaling.

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“…11 Recently, RGC-32 was reported to be a key mediator of lipid and glucose metabolism. [12][13][14] RGC-32 can activate the liver X receptor to induce expression of SREBP-1c and its target genes, facilitating de novo lipogenesis and leading to the development of hepatic steatosis. 12 Expression of RGC-32 can be induced by a high-fat diet (HFD) in vivo and glucose in vitro.…”

mentioning

confidence: 99%

“…[12][13][14] RGC-32 can activate the liver X receptor to induce expression of SREBP-1c and its target genes, facilitating de novo lipogenesis and leading to the development of hepatic steatosis. 12 Expression of RGC-32 can be induced by a high-fat diet (HFD) in vivo and glucose in vitro. RGC-32 in endothelial cells can upregulate expression of glucagon-like peptide 2 receptor and downregulate expression of glutaminefructose-6-phosphate aminotransferase (isomerizing) 1, as well as and solute carrier family 2 (facilitated glucose transporter), member 12, contributing to the maintenance of the homeostasis of blood glucose.…”

mentioning

confidence: 99%

New insights into the roles of RGC-32

Wang

2018

Cell Mol Immunol

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RGC-32 Deficiency Protects against Hepatic Steatosis by Reducing Lipogenesis

Cited by 22 publications

References 53 publications

The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting ß3‐adrenergic receptor/mTORC1 signaling

New insights into the roles of RGC-32

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