ArticleMetabolism: clinical and experimental2015
Chronic angiotensin AT2R activation prevents high-fat diet-induced adiposity and obesity in female mice independent of estrogen.
Article in Metabolism: clinical and experimental, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 32 citations in OpenAlex.
- Cold Exposure Exacerbates Cardiac Dysfunction in a Model of Heart Failure with Preserved Ejection Fraction in Male and Female C57Bl/6J Mice.Biomedicines · 2025Article
- Therapeutic opportunities in targeting the protective arm of the renin-angiotensin system to improve insulin sensitivity: a mechanistic review.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Unlocking the protective potential of the angiotensin type 2 receptor (ATBiochemical pharmacology · 2024Article
- Acute In Vivo Administration of Compound 21 Stimulates Akt and ERK1/2 Phosphorylation in Mouse Heart and Adipose Tissue.International journal of molecular sciences · 2023Article
- Angiotensin II type 2 receptor prevents extracellular matrix accumulation in human peritoneal mesothelial cell by ameliorating lipid disorder via LOX-1 suppression.Renal failure · 2022Article
- The Angiotensin ATPharmacological reviews · 2022Review
- Angiotensin II Type 2 Receptor: A Target for Protection Against Hypertension, Metabolic Dysfunction, and Organ Remodeling.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Activation of ATBritish journal of pharmacology · 2020Article
- Blackcurrant (Nutrients · 2020Article
- Role of angiotensin type 2 receptor in improving lipid metabolism and preventing adiposity.Molecular and cellular biochemistry · 2019Article
- Sex differences in the metabolic effects of the renin-angiotensin system.Biology of sex differences · 2019Review
- Chronic administration of the angiotensin type 2 receptor agonist C21 improves insulin sensitivity in C57BL/6 mice.Physiological reports · 2018Article
- Prenatal dexamethasone and postnatal high-fat diet have a synergistic effect of elevating blood pressure through a distinct programming mechanism of systemic and adipose renin-angiotensin systems.Lipids in health and disease · 2018Article
- The intricacies of the renin-angiotensin-system in metabolic regulation.Physiology & behavior · 2017Review
- Suppression of Resting Metabolism by the Angiotensin AT2 Receptor.Cell reports · 2016Article
- Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis.Signal transduction and targeted therapyArticle
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5 authors at 1 institution in 1 country.
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Abstract
objectiveObesity is a known risk factor for various metabolic disorders and cardiovascular diseases. Recently we demonstrated that female angiotensin AT2 receptor (AT2R) knockout mice on high-fat diet (HFD) had higher body weight and adiposity with a parallel reduction in estrogen (17,β-estradiol/E2). The present study investigated whether the anti-adiposity effects of the AT2R are estrogen-dependent in female mice.
methodsFemale C57BL/6 ovary-intact (Ovi) mice were treated with an AT2R agonist (C21, 0.3 mg/kg, daily i.p.). Ovariectomized (Ovx) mice, supplemented with E2 (5 μg/day, pellets implanted subcutaneously), were treated with an AT2R agonist (C21, 0.3 mg/kg, daily i.p.) or vehicle. After 4-days of pre-treatment with C21, Ovi and Ovx mice were placed on either normal diet (ND) or HFD while the C21 treatment continued for the next 10 days. For a long-term study, Ovi mice were placed on HFD and treated with C21 for 12 weeks.
resultsOvi mice fed the HFD had increased parametrial white adipose tissue (pWAT) weight, plasma free fatty acid and triglycerides compared to Ovi mice on ND. Ovariectomy alone caused similar changes in these parameters which were further increased by HFD-feeding. C21 treatment attenuated these HFD-induced changes in Ovi as well as Ovx mice. HFD also, increased the liver/body-weight ratio and decreased the liver expression of the β-oxidation enzyme, carnitine palmitoyltransferase 1 (CPT1-A). C21 treatment attenuated these changes as well. The long-term C21 treatment of Ovi mice lowered the HFD-induced body weight gain, increase in pWAT weight, parametrial adipocyte size and hyperinsulinemia induced by HFD. Finally, HFD drastically reduced urinary estrogen and the beneficial metabolic changes in response to C21-treatment occurred without significantly increasing urinary estrogen.
conclusionWe suggest that the pharmacological activation of AT2R by the agonist C21 reduces adiposity and body weight gain independent of estrogen in female mice. Improvement in fatty acid metabolism is a potential mechanism by which the AT2R exerts anti-adiposity effects.
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