Deletion of angiotensin II type I receptor reduces hepatic steatosis

Nabeshima, Yoshitaka; Tazuma, Susumu; Kanno, Keishi; Hyogo, Hideyuki; Chayama, Kazuaki

doi:10.1016/j.jhep.2009.01.018

Cited by 54 publications

(61 citation statements)

References 47 publications

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“…9A) and then starved for the next 24 h. As seen in Fig. 9C, Huh7 cells transfected with an miR-33a or miR-33a* mimic showed significantly lower levels of ␤-hydroxybutyrate, an end product of hepatic fatty acid oxidation (37), than cells transfected with a control mimic (CM). Interestingly, cells transfected with both miR-33a and miR-33a* showed slightly lower levels of ␤-hydroxybutyrate compared to cells transfected with either mimic alone, thus suggesting a shared regulation of fatty acid oxidation by both arms of the miR-33a/miR-33a* duplex.…”

Section: Resultsmentioning

confidence: 84%

A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression

Goedeke

Vales-Lara

Fenstermaker

et al. 2013

Molecular and Cellular Biology

129

126

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Section: Resultsmentioning

confidence: 84%

A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression

Goedeke

Vales-Lara

Fenstermaker

et al. 2013

Molecular and Cellular Biology

129

126

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“…3B). Moreover, we observed increased levels of b-hydroxybutyrate, an end product of hepatic fatty acid oxidation [19], in the medium of SRC-3 siR-NA-treated HepG2 cells as compared to control cells (Fig. 3C).…”

Section: Src-3 Knockdown Elevates Ppara Expressionmentioning

confidence: 81%

Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis

Wang

et al. 2011

Journal of Hepatology

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“…These groups also had increased β-oxidation due to reduced TNF-α levels and higher hepatic PPAR-α expression. The greatest increase was observed in the groups treated with telmisartan, which has recently been described as a partial PPAR-α agonist in the liver due to its AT 1 R-blocking property [31]. Additionally, experimental data reveal that mitochondrial dysfunction impairs β-oxidation [32].…”

Section: Discussionmentioning

confidence: 94%

Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet

et al. 2010

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The aim of the present study was to evaluate the effects of monotherapies and combinations of drugs on insulin sensitivity, adipose tissue morphology, and pancreatic and hepatic remodelling in C57BL/6 mice fed on a very HF (high-fat) diet. Male C57BL/6 mice were fed on an HF (60% lipids) diet or SC (standard chow; 10% lipids) diet for 10 weeks, after which time the following drug treatments began: HF-T (HF diet treated with telmisartan; 5.2 mg x kg-1 of body weight x day-1), HF-S (HF diet treated with sitagliptin; 1.08 g x kg-1 of body weight.day-1), HF-M (HF diet treated with metformin; 310.0 mg x kg-1 of body weight x day-1), HF-TM (HF diet treated with telmisartan+metformin), HF-TS (HF diet treated with telmisartan+sitagliptin) and HF-SM (HF diet treated with sitagliptin+metformin). Treated groups also had free access to the HF diet, and treatments lasted for 6 weeks. Morphometry, stereological tools, immunostaining, ELISA, Western blot analysis and electron microscopy were used. The HF diet yielded an overweight phenotype, an increase in oral glucose intolerance, hyperinsulinaemia, hypertrophied islets and adipocytes, stage 2 steatosis (>33%), and reduced liver PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) and GLUT-2 (glucose transporter-2) levels, concomitant with enhanced SREBP-1 (sterol-regulatory-element-binding protein-1) expression (P<0.0001). Conversely, all drug treatments resulted in significant weight loss, a reversal of insulin resistance, islet and adipocyte hypertrophy, and alleviated hepatic steatosis. Only the HF-T and HF-TS groups had body weights similar to the SC group at the end of the experiment, and the latter treatment reversed hepatic steatosis. Increased PPAR-alpha immunostaining in parallel with higher GLUT-2 and reduced SREBP-1 expression may explain the favourable hepatic outcomes. Restoration of adipocyte size was consistent with higher adiponectin levels and lower TNF-alpha (tumour necrosis factor-alpha) levels (P<0.0001) in the drug-treated groups. In conclusion, all of the drug treatments were effective in controlling the metabolic syndrome. The best results were achieved using telmisartan and sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-gamma agonism and PPAR-alpha activation in the liver with extended incretin action.

show abstract

Deletion of angiotensin II type I receptor reduces hepatic steatosis

Abstract: Our data indicate, in addition to pharmacological effect of ARBs on PPARgamma activation, a key biological role for AT1R in the regulation of hepatic lipid metabolism.

Cited by 54 publications

References 47 publications

A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression

A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression

Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis

Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet

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