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Diminazene Aceturate Attenuates Obesity and Promotes a Balance of the Renin‐Angiotensin System in Fat and Muscle Tissue in Young and Aged Rats on High Fat Diet
Author(s) -
Sakarya Yasemin,
Bruce Erin,
Morgan Drake,
Tümer Nihal,
Carter Christy S.,
Scarpace Philip J.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.717.7
Subject(s) - vasoprotective , endocrinology , medicine , renin–angiotensin system , adipose tissue , chemistry , obesity , white adipose tissue , body weight , angiotensin ii , lean body mass , blood pressure , nitric oxide
Obesity is a complex disorder, and increases the risk for a number of chronic diseases, including diabetes and cardiovascular diseases. Renin‐angiotensin system (RAS) is considered the major regulator of cardiovascular homeostasis. Recent studies suggest stimulation of the vasoprotective ACE2/Ang (1–7)/Mas axis of the RAS leads to significant reductions in body weight in obese animal models. We have shown that Diminazene Aceturate, a novel ACE2 activator, significantly reduced body weight of both young and aged rats fed 60% high fat diet. Notably we observed a significant loss of fat mass with a preservation of lean mass. We hypothesize that maintaining balance between the ACE/AngII/AT1R axis and vasoprotective components in muscle and white adipose tissues will prevent much of the associated pathophysiology of the obesity. Male Fisher 344 × Brown Norway rats, ages 4 (n=12) and 23 months (n=17) were fed 60% high fat diet for one week, whereupon, animals were further divided, and given either 15mg/kg/day DIZE s.c. (Young DIZE, n=6; Old DIZE, n=9) or vehicle (Young Control, n=6; Old Control, n=8). Body weight and food intake were measured throughout the experiment. Time Domain‐Nuclear Magnetic Resonance (TD‐NMR) was used to assess body composition 1 week and 3 weeks after the start of DIZE treatment. With the aim of elucidating the effect of DIZE on the relationship between RAS components, AT1R, AT2R, MasR, ACE, ACE2 mRNA were measured in retroperitoneal white adipose tissue (RTWAT), and tibialis anterior (TA) muscle, using qPCR. Relative quantitation of RTWAT mRNA expression showed DIZE treatment significantly increased AT2R (5 fold) and MasR (1 fold) in old animals when compared to non‐treated controls. AT1R expression was significantly increased in the muscle of old rats treated with DIZE; however, the AT1R/AT2R ratio was not different from control. Furthermore, the ACE/ACE2 ratio was decreased in the muscle tissue in both young and old rats. Our data suggests DIZE may be a useful tool in maintaining the balance between the two opposing arms of the RAS, and will be an effective treatment to ameliorate obesity and related disorders. Support or Funding Information Hypertension Center T32 Post Doctoral training grant, North Florida/South Georgia Veterans Health System (Research/GRECC), and National Institute's of Health Grant NIH DK 091710