Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor γ and hepatocyte nuclear factor 4α

Malerød, Lene; Sporstøl, Marita; Juvet, Lene Kristine; Mousavi, Ali; Gjøen, Tor; Berg, Trond

doi:10.1016/s0006-291x(03)00819-2

Cited by 74 publications

(57 citation statements)

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“…These include altered body composition (5,10), decreased intramyocellular and intrahepatocellular triglyceride content (6,11,12), reduction in circulating free fatty acid (FFA) levels (5,13), and decreased production and/or actions of circulating proinflammatory proteins (14,15). In addition, TZD treatment alters the expression of many metabolically important genes in adipose tissue, liver, and muscle, as demonstrated both in insulin resistant animal models (16,17) and in some cell culture systems (18,19). Among those genes whose expression is altered in muscle and liver are genes that regulate glucose metabolism and fatty acid handling (16).…”

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confidence: 99%

Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes

et al. 2004

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Whereas thiazolidinediones (TZDs) are known to rapidly improve insulin action in animals, short durations of TZD therapy have never been studied in humans. Among the many known actions of TZDs, increased circulating levels of the high molecular weight (HMW) multimer of adiponectin may be an important insulinsensitizing mechanism. We examined the effects of only 21 days of 45 mg of pioglitazone (P؉) versus placebo (P؊) in nine subjects with type 2 diabetes (HbA 1c , 10.9 ؎ 0.6%; BMI, 31.9 ؎ 1.5 kg/m 2 ). Total adiponectin levels increased by approximately twofold in P؉ in association with increased adipose tissue gene expression. However, plasma free fatty acid and glucose levels were unchanged, and there were only minimal changes in other "adipokines." Glucose fluxes ([3-3 H]glucose infusion) were measured during 6-h euglycemic (5 mmol/l) "pancreatic clamp" studies (somatostatin/glucagon/growth hormone) with stepped insulin levels. Pioglitazone induced marked decreases in endogenous glucose production (P؉ ‫؍‬ 0.9 ؎ 0.1 vs. P؊ ‫؍‬ 1.7 ؎ 0.3 mg ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.05) at physiologic hyperinsulinemia (ϳ50 U/ml), which was highly correlated with an increased ratio of HMW adiponectin/total levels (r 2 ‫؍‬ 0.90). Maximal insulin stimulation (ϳ400 U/ml) revealed pioglitazone-associated increases in glucose uptake (P؉ ‫؍‬ 10.5 ؎ 0.9 vs. P؊ ‫؍‬ 8.9 ؎ 0.8 mg ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.05), which did not correlate with HMW or total adiponectin levels. Thus, only 21 days of pioglitazone therapy improved insulin action in humans with type 2 diabetes. Increased abundance of the HMW adiponectin multimer may contribute to the hepatic insulin-sensitizing effects of these agents.

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confidence: 99%

Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes

et al. 2004

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“…We also found that an LXR agonist brought about no changes in SR-B mRNA levels in macrophages (data not shown). Recently, other researchers have demonstrated that SR-B expression in atherosclerotic lesion macrophages is regulated by PPAR 14) and activated PPAR transcriptionally stimulates hepatic SR-B expression 32) . The SR-B expression in macrophages induced by pioglitazone and telmisartan in our study could be due to a similar mechanism.…”

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confidence: 99%

Telmisartan Enhances Cholesterol Efflux from THP-1 Macrophages by Activating PPARγ

Nakaya

Ayaori

Hisada

et al. 2007

JAT

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Aim:The ATP binding cassette transporters A1 and G1 (ABCA1/G1) and scavenger receptor class B type (SR-B ) are key molecules in cholesterol efflux and atherogenesis. These genes are regulated by peroxisome proliferator-activated receptor (PPAR ) and liver X receptor (LXR). Telmisartan is an angiotensin type 1 receptor blocker which has been reported to act as a ligand for PPAR . We investigated whether PPAR -activating ARBs affect the expression of these genes and cholesterol efflux from macrophages. Methods and Results: Telmisartan increased ABCA1, ABCG1 and SR-B mRNA levels in THP-1 macrophages in a dose-and time-dependent fashion. It also increased their protein levels and enhanced apoA--and HDL-mediated cholesterol efflux from macrophages. The knockdown of PPAR by siRNA abolished the telmisartan-induced expression of these genes. The knockdown of LXR resulted in the complete and partial abolishment of telmisartan-induced ABCA1 and ABCG1 expression, respectively. We also demonstrated that telmisartan-induced SR-B expression was dependent on the PPAR pathway but not on the LXR pathway. A luciferase assay using an ABCA1 promoter construct showed that telmisartan activated ABCA1 transcription, which was abolished if the LXR binding element was mutated, indicating that increased ABCA1 transcription by telmisartan is LXRdependent. Conclusion: Our results showed that telmisartan enhanced both apoA--and HDL-mediated cholesterol efflux from macrophages by increasing ABCA1, ABCG1 and SR-B expression via PPAR -dependent and LXR-dependent/independent pathways.

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“…SR-BI mediates the selective uptake of cholesteryl esters from HDL into the liver (213). PPARs and FXR regulate the expression of SR-BI (214,215). Therefore, the decrease in PPAR/RXR and FXR/ RXR activity in the liver could mediate the decrease in SR-BI expression during the APR (Table 5).…”

Section: Consequences Of Decreased Expression Of Liposensorsmentioning

confidence: 99%

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Khovidhunkit

Kim

Memon

et al. 2004

Journal of Lipid Research

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Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor γ and hepatocyte nuclear factor 4α

Cited by 74 publications

References 50 publications

Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes

Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes

Telmisartan Enhances Cholesterol Efflux from THP-1 Macrophages by Activating PPARγ

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

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Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor γ and hepatocyte nuclear factor 4α

Cited by 74 publications

References 50 publications

Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes

Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes

Telmisartan Enhances Cholesterol Efflux from THP-1 Macrophages by Activating PPAR&gamma;

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

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Telmisartan Enhances Cholesterol Efflux from THP-1 Macrophages by Activating PPARγ