Effects of Early Administration of Conjugated Linoleic Acid on Development of Obesity in NescientBasic Helix‐Loop‐Helix 2 Knockout Mice

Abstract

Childhood obesity has steadily increased in the past 30 years and is associated with increased risk of chronic metabolic diseases. This study aimed to determine effects of conjugated linoleic acid (CLA) exposure during growth period on development of inactivity-induced obesity by investigating the molecular targets on skeletal muscle in nescient basic helix-loop-helix 2 knock-out (N2KO) mice, a unique adult-onset inactivity induced obesity model. 4-week-old male N2KO and wild-type mice were fed either control or CLA containing diet (0.5%) for 4-weeks, and then all animals were fed control diet for 8-weeks. Voluntary activity and glucose tolerance were examined every 4 weeks and markers for muscle energy metabolism were determined from the gastrocnemius. CLA fed wild-type animals significantly prevented a reduction of voluntary activity and glucose intolerance compared to control groups at week 12. CLA feeding up-regulated AMP-activated protein kinase (AMPK) activation, peroxisome proliferator-activated receptor gamma co-activator 1a (PGC-1a, a master regulator of mitochondrial biogenesis), peroxisome proliferator-activated receptor-δ (PPARd) and mitochondrial transcription factor A (Tfam) in wild-type animals compared to controls, but not in obese animals. These results suggest that early exposure to CLA during growth modulates muscle energy metabolism via enhancing mitochondriogenic factors, resulting in increased voluntary activity and improved glucose metabolisms in normal animals, but not in genetically predisposed obese mice.