title: The AIN-76A defined rodent diet accelerates the development of heart failure in SHHF rats: a cautionary note on its use in cardiac studies.
abstract: Previous studies from our laboratory have shown positive benefits of linoleic acid (LA) feeding for attenuation of rat heart failure (HF). However, another research group concluded LA feeding was detrimental to cardiac function, using the American Institute of Nutrition 76A (AIN) diet as a background diet for the experimental animals only. To reconcile these conflicting results and determine whether (i) AIN has effects on cardiovascular function, and (ii) AIN reverses the positive effects of LA feeding, studies were performed using spontaneously hypertensive heart failure (SHHF) rats in both a survival study with lifetime feeding of AIN (control: Purina 5001) and a 2 × 2 factorial design for 6 weeks in young male SHHF rats with background diet and LA as variables. During a lifetime of AIN feeding, mortality from heart failure is significantly accelerated, cardiolipin altered and triglycerides increased. In young rats, 6 weeks on the AIN diet promoted increased systolic and diastolic blood pressure, increased fed and fasting blood glucose, increased serum inflammatory eicosanoids, decreased docosahexanoic acid, increased posterior wall thickness in diastole and an altered cardiolipin subspecies profile. The addition of LA to the AIN diet was able to rescue blood pressure. However, the combination increased retroperitoneal fat mass, body weight and fed blood glucose beyond the levels with the AIN diet alone. Because the AIN diet has wide ranging effects on cardiovascular parameters, our results suggest that it should not be used in animal studies involving the cardiovascular system unless induction of cardiac dysfunction is the desired outcome.
authors.affiliation: Department of Integrative Physiology, University of Colorado Cardiovascular Institute, University of Colorado at Boulder, Boulder, CO, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Rees
authors.forename: R A
authors.initials: RA
authors.lastname: Gioscia-Ryan
authors.forename: S A
authors.initials: SA
authors.lastname: McCune
authors.forename: J C
authors.initials: JC
authors.lastname: Browder
authors.forename: D K
authors.initials: DK
authors.lastname: Zachman
authors.forename: A J
authors.initials: AJ
authors.lastname: Chicco
authors.forename: C A
authors.initials: CA
authors.lastname: Johnson
authors.forename: R C
authors.initials: RC
authors.lastname: Murphy
authors.forename: R L
authors.initials: RL
authors.lastname: Moore
authors.forename: G C
authors.initials: GC
authors.lastname: Sparagna
mesh_terms: D000821:Animal Feed / Q000032:analysis*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004032:Diet; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D008297:Male; D009752:Nutritional Status; D051381:Rats; D011918:Rats, Inbred SHR
keywords: blood pressure; cardiolipin; docosahexanoic acid; eicosanoid; high-linoleoyl safflower oil; linoleic acid; spontaneously hypertensive; sucrose