title: Angiotensin 1-7 as means to prevent the metabolic syndrome: lessons from the fructose-fed rat model.
abstract: We studied the effects of chronic angiotensin 1-7 (Ang 1-7) treatment in an experimental model of the metabolic syndrome, i.e., rats given high-fructose/low-magnesium diet (HFrD). Rats were fed on HFrD for 24 weeks with and without Ang 1-7 (576 µg/kg/day, s.c., Alzet pumps). After 6 months, Ang 1-7-treated animals had lower body weight (-9.5%), total fat mass (detected by magnetic resonance imaging), and serum triglycerides (-51%), improved glucose tolerance, and better insulin sensitivity. Similar metabolic effects were also evident, albeit in the absence of weight loss, in rats first exposed to HFrD for 5 months and then subjected to short-term (4 weeks) treatment with Ang 1-7. Six months of Ang 1-7 treatment were associated with lower plasma renin activity (-40%) and serum aldosterone (-48%), less hepatosteatatitis, and a reduction in epididymal adipocyte volume. The marked attenuation of macrophage infiltration in white adipose tissue (WAT) was associated with reduced levels of the pP65 protein in the epididymal fat tissue, suggesting less activation of the nuclear factor-κB (NFκB) pathway in Ang 1-7-treated rats. WAT from Ang 1-7-treated rats showed reduced NADPH-stimulated superoxide production. In single muscle fibers (myofibers) harvested and grown ex vivo for 10 days, myofibers from HFrD rats gave rise to 20% less myogenic cells than the Ang 1-7-treated rats. Fully developed adipocytes were present in most HFrD myofiber cultures but entirely absent in cultures from Ang 1-7-treated rats. In summary, Ang 1-7 had an ameliorating effect on insulin resistance, hypertriglyceridemia, fatty liver, obesity, adipositis, and myogenic and adipogenic differentiation in muscle tissue in the HFrD rats.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yonit
authors.initials: Y
authors.lastname: Marcus
authors.forename: Gabi
authors.initials: G
authors.lastname: Shefer
authors.forename: Keren
authors.initials: K
authors.lastname: Sasson
authors.forename: Fortune
authors.initials: F
authors.lastname: Kohen
authors.forename: Rona
authors.initials: R
authors.lastname: Limor
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.forename: Nava
authors.initials: N
authors.lastname: Nevo
authors.forename: Inbal
authors.initials: I
authors.lastname: Biton
authors.forename: Michal
authors.initials: M
authors.lastname: Bach
authors.forename: Tamara
authors.initials: T
authors.lastname: Berkutzki
authors.forename: Matityahu
authors.initials: M
authors.lastname: Fridkin
authors.forename: Dafna
authors.initials: D
authors.lastname: Benayahu
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shechter
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000803:Angiotensin I / Q000008:administration & dosage*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004822:Epididymis / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000517:prevention & control*; D018482:Muscle, Skeletal; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000008:administration & dosage*; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D004040:Dietary Carbohydrates; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D005632:Fructose; D000803:Angiotensin I; D048049:Extracellular Signal-Regulated MAP Kinases; C118790:angiotensin I (1-7)