Regulation of adiponectin receptors in hepatocytes by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

Sun, Xiaoyu; Han, Renji; Wang, Zhong Min; Chen, Y.

doi:10.1007/s00125-006-0228-1

Cited by 51 publications

(36 citation statements)

References 33 publications

(44 reference statements)

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“…Such treatment induced profound adipogenic transformation of the gene expression pattern in hepatocytes. Rosiglitazone has been shown to increase the mRNA and protein levels of ADIPOR2 in HepG2 cells (47), but expression of both ADIPOR1 and ADIPOR2 were unchanged in the present study. It may seem paradoxical that PPAR␥ agonists markedly lower liver fat content in humans (48), although PPAR␥2 is overexpressed in the human fatty liver.…”

Section: Discussioncontrasting

confidence: 73%

Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects

Westerbacka

Kolak²,

Kiviluoto³

et al. 2007

Diabetes

308

224

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OBJECTIVE-The objective of this study is to quantitate expression of genes possibly contributing to insulin resistance and fat deposition in the human liver.RESEARCH DESIGN AND METHODS-A total of 24 subjects who had varying amounts of histologically determined fat in the liver ranging from normal (n ϭ 8) to steatosis due to a nonalcoholic fatty liver (NAFL) (n ϭ 16) were studied. The mRNA concentrations of 21 candidate genes associated with fatty acid metabolism, inflammation, and insulin sensitivity were quantitated in liver biopsies using real-time PCR. In addition, the subjects were characterized with respect to body composition and circulating markers of insulin sensitivity. . PPAR␥ coactivator 1 (PGC1) was significantly lower in subjects with NAFL than in those without. Genes significantly associated with obesity included nine genes: plasminogen activator inhibitor 1, PPAR␥, PPAR␦, MCP-1, CCL3 (macrophage inflammatory protein [MIP]-1␣), PPAR␥2, carnitine palmitoyltransferase (CPT1A), FABP4, and FABP5. The following parameters were associated with liver fat independent of obesity: serum adiponectin, insulin, C-peptide, and HDL cholesterol concentrations and the mRNA concentrations of MCP-1, MIP-1␣, ACSL4, FABP4, FABP5, and LPL. RESULTS-TheCONCLUSIONS-Genes involved in fatty acid partitioning and binding, lipolysis, and monocyte/macrophage recruitment and inflammation are overexpressed in the human fatty liver.

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Section: Discussioncontrasting

confidence: 73%

Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects

Westerbacka

Kolak²,

Kiviluoto³

et al. 2007

Diabetes

308

224

View full text Add to dashboard Cite

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“…Furthermore, distinct regulation of ADIPOR1/2 has been recently shown in that rosiglitazone enhanced transcription from the ADIPOR2, but not ADIPOR1 promoter in HepG2 cells through an interaction with a glucocorticoid receptor (GR) element. 49 In conclusion, our studies show enhanced hepatic ADIPOR1 and ADIPOR2 mRNA expression in insulin-resistant obese humans and suggest differential regulation of ADIPOR1/2 by FOXO1. Although mainly descriptive in nature, these data may add to previous knowledge obtained from studies in cell lines and animals and help to understand the regulation of adiponectin receptors in humans.…”

Section: Discussionsupporting

confidence: 51%

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

et al. 2010

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Objective: Adiponectin signalling attenuates insulin resistance (IR) and steatosis hepatis in animal models. As adiponectin receptor (ADIPOR)1 and ADIPOR2 are critical components in the adiponectin signalling cascade, we studied hepatic ADIPOR1/2 mRNA levels in humans and their relation to IR. Design: We determined metabolic risk factors and levels of hepatic mRNA transcribed from ADIPOR1, ADIPOR2 and FOXO1, a putative up-stream regulator, in 43 and 34 obese subjects with low and high homeostasis model assessment-IR, respectively. Results: Plasma adiponectin and metabolic risk factors showed associations with IR as expected. Both hepatic ADIPOR1 and ADIPOR2 mRNA expression levels were higher in insulin-resistant subjects (Po0.0035). ADIPOR1 mRNA correlated with FOXO1 mRNA in obese insulin resistant (P ¼ 0.0034), but not insulin-sensitive subjects, while no correlations of ADIPOR2 with FOXO1 mRNA were noted. FOXO1 enhanced transcription from the ADIPOR1, but not the ADIPOR2 promoter in HepG2 cells. Conclusion: Increased hepatic ADIPOR1 and ADIPOR2 mRNA in insulin-resistant obese subjects may, at least in part, reflect a compensatory mechanism for reduced plasma adiponectin. FOXO1 may contribute to enhanced ADIPOR1, but not ADIPOR2 transcription in IR.

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“…Transient transfection was performed with the polyethylenimine method for HEK293T and Hela cells [48]. The methods for cell fixation, immunofluorescence staining and confocal analyses were described previously [23].…”

Section: Plasmidsmentioning

confidence: 99%

PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus

et al. 2011

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Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQR11 of the progestin and AdipoQ receptors family. PAQR10 and PAQR11 are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQR11 stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent manner. Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQR11 can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQR11 is in an active state. Consistently, knockdown of PAQR10 and PAQR11 reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQR11 are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQR11. The simulation of ERK phosphorylation by overexpressed PAQR10/ PAQR11 is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQR11. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11.

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Regulation of adiponectin receptors in hepatocytes by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

Cited by 51 publications

References 33 publications

Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects

Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus

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