Ribel-Madsen Amalie, Ribel-Madsen Rasmus, Brøns Charlotte, Newgard Christopher B, Vaag Allan A, Hellgren Lars I
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Danish Diabetes Academy, Odense, Denmark.
Physiol Rep. 2016 Oct;4(19). doi: 10.14814/phy2.12977.
We hypothesized that an increased, incomplete fatty acid beta-oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5-day high-fat, high-calorie diet. We demonstrated that LBW men had higher C2 and C4-OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta-oxidation relative to the tricarboxylic acid cycle flux. Also, they had higher C6-DC, C10-OH/C8-DC, and total hydroxyl-/dicarboxyl-acylcarnitine levels, which may suggest an increased fatty acid omega-oxidation in the liver. Furthermore, LBW and NBW men decreased several acylcarnitine levels in response to overfeeding, which is likely a result of an upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10-OH/C8-DC and total hydroxyl-/dicarboxyl-acylcarnitine levels tended to be negatively associated with the serum insulin level, and the total hydroxyl-/dicarboxyl-acylcarnitine level additionally tended to be negatively associated with the hepatic insulin resistance index. This indicates that an increased fatty acid omega-oxidation could be a compensatory mechanism to prevent an accumulation of lipid species that impair insulin signaling.
我们推测，线粒体中脂肪酸β-氧化增加且不完全可能是导致胰岛素抵抗的代谢事件的一部分，从而与正常出生体重（NBW）个体相比，低出生体重（LBW）个体患2型糖尿病的风险增加。因此，我们在18名低出生体重男性和25名正常出生体重男性摄入等热量对照饮食以及5天高脂肪、高热量饮食后，测量了45种酰基肉碱的空腹血浆水平。我们发现，与正常出生体重男性相比，低出生体重男性在对照饮食后C2和C4-OH水平更高，这表明相对于三羧酸循环通量，脂肪酸β-氧化增加。此外，他们的C6-DC、C10-OH/C8-DC以及总羟基/二羧基酰基肉碱水平更高，这可能表明肝脏中脂肪酸ω-氧化增加。此外，低出生体重和正常出生体重男性在过度喂养后几种酰基肉碱水平降低，这可能是由于饮食挑战导致脂肪酸氧化上调的结果。此外，C10-OH/C8-DC和总羟基/二羧基酰基肉碱水平往往与血清胰岛素水平呈负相关，总羟基/二羧基酰基肉碱水平还往往与肝脏胰岛素抵抗指数呈负相关。这表明脂肪酸ω-氧化增加可能是一种补偿机制，以防止损害胰岛素信号传导的脂质种类积累。
