title: Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin II type 1a receptor.
abstract: Given that angiotensin II (AII) type 1 and 2 receptors (Agtr1 and Agtr2) are expressed in adipose tissue, AII may act directly on adipose tissue. However, regardless of whether AII directly modulates adipose tissue growth and metabolism in vivo and, if so, whether it is mediated via Agtr1 are still matters of debate. To understand the functional role of Agtr1 in adipose tissue growth and metabolism in vivo, we examined the metabolic phenotypes of mice lacking Agtr1a (Agtr1a-/- mice) during a high-fat diet. The Agtr1a-/- mice exhibited the attenuation of diet-induced body weight gain and adiposity, and insulin resistance relative to wild-type littermates (Agtr1a+/+ mice). They also showed increased energy expenditure accompanied by sympathetic activation, as revealed by increased rectal temperature and oxygen consumption, increased expression of uncoupling protein-1 mRNA in brown adipose tissue, and increased urinary catecholamine excretion. The heterozygous Agtr1a-deficient mice (Agtr1a+/- mice) also exhibited metabolic phenotypes similar to those of Agtr1a-/- mice. Using mouse embryonic fibroblasts derived from Agtr1a+/+ and Agtr1a-/- mice, we found no significant difference between genotypes in the ability to differentiate into lipid-laden mature adipocytes. In primary cultures of mouse mature adipocytes, AII increased the expression of mRNAs for some adipocytokines, which was abolished by pharmacological blockade of Agtr1. This study demonstrates that Agtr1a-/- mice exhibit attenuation of diet-induced weight gain and adiposity through increased energy expenditure. The data also suggest that AII does not affect directly adipocyte differentiation, but can modulate adipocytokine production via Agtr1.
authors.affiliation: Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kouyama
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Junko
authors.initials: J
authors.lastname: Nishida
authors.forename: Miyako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Toyoda
authors.forename: Minako
authors.initials: M
authors.lastname: Kiso
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiwata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Yoshimasa
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004032:Diet; D002149:Energy Intake; D004734:Energy Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D010101:Oxygen Consumption / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D015430:Weight Gain
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2