TY - JOUR
T1 - Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity
AU - Ratner, Cecilia
AU - Madsen, Andreas Nygaard
AU - Kristensen, Line Vildbrad
AU - Skov, Louise Julie
AU - Pedersen, Katrine Seide
AU - Mortensen, Ole Hartvig
AU - Knudsen, Gitte Moos
AU - Raun, Kirsten
AU - Holst, Birgitte
N1 - Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed a Western diet for 76 days. Body composition was assessed by magnetic resonance imaging scans, and as expected, the OP rats developed a higher degree of fat accumulation compared with OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared with OR rats, indicating an impaired ability to oxidize fat. The OP rats had lower expression of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR rats, which could explain the higher fat accumulation and RER values. Basal metabolic parameters were also examined in juvenile OP and OR rats before and during the introduction of the Western diet. Juvenile OP rats likewise had higher RER values, indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive to the orexigenic effects of ghrelin as well as ghrelin-induced attenuation of activity and energy expenditure. Thus increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to be a contributing factor.
AB - To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed a Western diet for 76 days. Body composition was assessed by magnetic resonance imaging scans, and as expected, the OP rats developed a higher degree of fat accumulation compared with OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared with OR rats, indicating an impaired ability to oxidize fat. The OP rats had lower expression of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR rats, which could explain the higher fat accumulation and RER values. Basal metabolic parameters were also examined in juvenile OP and OR rats before and during the introduction of the Western diet. Juvenile OP rats likewise had higher RER values, indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive to the orexigenic effects of ghrelin as well as ghrelin-induced attenuation of activity and energy expenditure. Thus increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to be a contributing factor.
U2 - 10.1152/ajpregu.00219.2014
DO - 10.1152/ajpregu.00219.2014
M3 - Journal article
C2 - 25855307
SN - 0363-6119
VL - 308
SP - R973-R982
JO - American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
JF - American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
IS - 11
ER -
