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 - 2015/4/8

Y1 - 2015/4/8

N2 - In order 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 MRI scans and as expected the OP rats developed a higher degree of fat accumulation compared to OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared to 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 to 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 ghrelin's orexigenic effects 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, while ghrelin sensitivity did not seem to be a contributing factor.

AB - In order 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 MRI scans and as expected the OP rats developed a higher degree of fat accumulation compared to OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared to 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 to 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 ghrelin's orexigenic effects 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, while 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

VL - 308

SP - R973-R982

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 11

ER -