ArticleBritish journal of pharmacology2010
Irbesartan treatment up-regulates hepatic expression of PPARalpha and its target genes in obese Koletsky (fa(k)/fa(k)) rats: a link to amelioration of hypertriglyceridaemia.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 29 citations in OpenAlex.
- A Review of Animal Models for Studying Bone Health in Type-2 Diabetes Mellitus (T2DM) and Obesity.International journal of molecular sciences · 2024Review
- Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease.International journal of molecular sciences · 2023Review
- PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A.Oncology research · 2023Article
- Effects of hypertension and antihypertensive treatments on sulfatide levels in serum and its metabolism.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Lipidized prolactin-releasing peptide improved glucose tolerance in metabolic syndrome: Koletsky and spontaneously hypertensive rat study.Nutrition & diabetes · 2018Article
- Linking atrial fibrillation with non-alcoholic fatty liver disease: potential common therapeutic targets.Oncotarget · 2017Review
- Peroxisome proliferator-activated receptor α-dependent renoprotection of murine kidney by irbesartan.Clinical science (London, England : 1979) · 2016Article
- The role of angiotensin II in nonalcoholic steatohepatitis.Molecular and cellular endocrinology · 2013Review
- Improvement of metabolic syndrome by irbesartan via the PPARγ/HGF pathway in apolipoprotein E knockout mice.Biomedical reports · 2013Article
- Bilobetin ameliorates insulin resistance by PKA-mediated phosphorylation of PPARα in rats fed a high-fat diet.British journal of pharmacology · 2012Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
background and purposeHypertriglyceridaemia is associated with an increased risk of cardiovascular disease. Irbesartan, a well-established angiotensin II type 1 receptor (AT(1)) blocker, improves hypertriglyceridaemia in rodents and humans but the underlying mechanism of action is unclear. EXPERIMENTAL APPROACH: Male obese Koletsky (fa(k)/fa(k)) rats, which exhibit spontaneous hypertension and metabolic abnormalities, received irbesartan (40 mg x kg(-1) x day(-1)) or vehicle by oral gavage over 7 weeks. Adipocyte-derived hormones in plasma were measured by ELISA. Gene expression in liver and other tissues was assessed by real-time PCR and Western immunoblotting. KEY
resultsIn Koletsky (fa(k)/fa(k)) rats irbesartan lowered plasma concentrations of triglycerides and non-esterified fatty acids, and decreased plasma insulin concentrations and the homeostasis model assessment of insulin resistance index. However, this treatment did not affect food intake, body weight, epididymal white adipose tissue weight, adipocyte size and plasma leptin concentrations, although plasma adiponectin was decreased. Irbesartan up-regulated hepatic expression of mRNAs corresponding to peroxisome proliferator-activated receptor (PPAR)alpha and its target genes (carnitine palmitoyltransferase-1a, acyl-CoA oxidase and fatty acid translocase/CD36) that mediate hepatic fatty acid uptake and oxidation; the increase in hepatic PPARalpha expression was confirmed at the protein level. In contrast, irbesartan did not affect expression of adipose PPARgamma and its downstream genes or hepatic genes that mediate fatty acid synthesis. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that irbesartan treatment up-regulates PPARalpha and several target genes in liver of obese spontaneously hypertensive Koletsky (fa(k)/fa(k)) rats and offers a novel insight into the lipid-lowering mechanism of irbesartan.
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