title: Obesity and gastrointestinal hormones-dual effect of angiotensin II receptor blockade and a partial agonist of PPAR-γ.
abstract: Obesity is strongly associated with type 2 diabetes, hypertension, and hyperlipidemia, which is one of the leading causes of mortality and morbidity worldwide. It is now clear that gut hormones play a role in the regulation of body weight and represent therapeutic targets for the future treatment of obesity. Recent evidence demonstrated that dysregulation of adipocytokine functions seen in abdominal obesity may be involved in the pathogenesis of the metabolic syndrome. Angiotensinogen, the precursor of angiotensin (Ang) II, is produced primarily in the liver, but also in adipose tissue, where it is up-regulated during the development of obesity and involved in blood pressure regulation and adipose tissue growth. Importantly, blockade of the RAS attenuates weight gain and adiposity by enhanced energy expenditure. The favorable metabolic effects of telmisartan have been related to its Ang II receptor blockade and action as a partial agonist of peroxisome proliferators activated receptor (PPAR)-γ. PPARγ plays an important role in regulating carbohydrate and lipid metabolism, and ligands for PPARγ can improve insulin sensitivity and reduce triglyceride levels. We designed a comparative study of telmisartan and losartan in ApoE-deficient mice. Treatment with telmisartan or losartan significantly reduced the development of lipid-rich plaque. However, treatment with telmisartan significantly improved endothelial dysfunction and inhibited lipid accumulation in the liver. These favorable characteristics of telmisartan might be due to its action as a partial agonist of PPAR-γ, beyond its blood pressure-lowering effect, through Ang II blockade, which may be called "metabosartan".
authors.affiliation: Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. nakagami@gts.med.osaka-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D005768:Gastrointestinal Hormones; D047495:PPAR gamma; D017228:Hepatocyte Growth Factor