title: Potential effect of angiotensin II receptor blockade in adipose tissue and bone.
abstract: 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, and also in adipose tissue, where it is up-regulated during the development of obesity and involved in blood pressure regulation and adipose tissue growth. Blockade of renin-angiotensin system (RAS) attenuates weight gain and adiposity by enhanced energy expenditure, and 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. Similarly, bone metabolism is closely regulated by hormones and cytokines, which have effects on both bone resorption and deposition. It is known that the receptors of Ang II are expressed in culture osteoclasts and osteoblasts, and Ang II is postulated to be able to act upon the cells involved in bone metabolism. In in vitro system, Ang II induced the differentiation and activation of osteoclasts responsible for bone resorption. Importantly, it was demonstrated by the sub-analysis of a recent clinical study that the fracture risk was significantly reduced by the usage of angiotensin-converting enzyme inhibitors. To treat the subgroups of hypertensive patients with osteoporosis RAS can be considered a novel target.
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, 2-1 Yamada-oka, Suita 565-0871, Japan. nakagami@gts.med.osaka-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Mariana Kiomy
authors.initials: MK
authors.lastname: Osako
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy; D047495:PPAR gamma / Q000819:agonists; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D047495:PPAR gamma