TY - JOUR
T1 - Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart
AU - Young, Martin E.
AU - Guthrie, Patrick H.
AU - Razeghi, Peter
AU - Leighton, Brendan
AU - Abbasi, Shahrzad
AU - Patil, Sarita
AU - Youker, Keith A.
AU - Taegtmeyer, Heinrich
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - We investigated whether decreased responsiveness of the heart to physiological increases in fatty acid availability results in lipid accumulation and lipotoxic heart disease. Lean and obese Zucker rats were either fed ad libitum or fasted overnight. Fasting increased plasma nonesterified fatty acid levels in both lean and obese rats, although levels were greatest in obese rats regardless of nutritional status. Despite increased fatty acid availability, the mRNA transcript levels of peroxisome proliferator-activated receptor (PPAR)-α-regulated genes were similar in fed lean and fed obese rat hearts. Fasting increased expression of all PPAR-α-regulated genes in lean Zucker rat hearts, whereas, in obese Zucker rat hearts, muscle carnitine palmitoyltransferase and medium-chain acyl-CoA dehydrogenase were unaltered with fasting. Rates of oleate oxidation were similar for hearts from fed rats. However, fasting increased rates of oleate oxidation only in hearts from lean rats. Dramatic lipid deposition occurred within cardiomyocytes of obese, but not lean, Zucker rats upon fasting. Cardiac output was significantly depressed in hearts isolated from obese rats compared with lean rats, regardless of nutritional status. Fasting increased cardiac output in hearts of lean rats only. Thus, the heart's inability to increase fatty acid oxidation in proportion to increased fatty acid availability is associated with lipid accumulation and contractile dysfunction of the obese Zucker rat.
AB - We investigated whether decreased responsiveness of the heart to physiological increases in fatty acid availability results in lipid accumulation and lipotoxic heart disease. Lean and obese Zucker rats were either fed ad libitum or fasted overnight. Fasting increased plasma nonesterified fatty acid levels in both lean and obese rats, although levels were greatest in obese rats regardless of nutritional status. Despite increased fatty acid availability, the mRNA transcript levels of peroxisome proliferator-activated receptor (PPAR)-α-regulated genes were similar in fed lean and fed obese rat hearts. Fasting increased expression of all PPAR-α-regulated genes in lean Zucker rat hearts, whereas, in obese Zucker rat hearts, muscle carnitine palmitoyltransferase and medium-chain acyl-CoA dehydrogenase were unaltered with fasting. Rates of oleate oxidation were similar for hearts from fed rats. However, fasting increased rates of oleate oxidation only in hearts from lean rats. Dramatic lipid deposition occurred within cardiomyocytes of obese, but not lean, Zucker rats upon fasting. Cardiac output was significantly depressed in hearts isolated from obese rats compared with lean rats, regardless of nutritional status. Fasting increased cardiac output in hearts of lean rats only. Thus, the heart's inability to increase fatty acid oxidation in proportion to increased fatty acid availability is associated with lipid accumulation and contractile dysfunction of the obese Zucker rat.
UR - http://www.scopus.com/inward/record.url?scp=0036326045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036326045&partnerID=8YFLogxK
U2 - 10.2337/diabetes.51.8.2587
DO - 10.2337/diabetes.51.8.2587
M3 - Article
C2 - 12145175
AN - SCOPUS:0036326045
SN - 0012-1797
VL - 51
SP - 2587
EP - 2595
JO - Diabetes
JF - Diabetes
IS - 8
ER -