Context: The molecular mechanisms behind diet-induced metabolic improvements remain to be studied. The Objective was to investigate whether expression of proteins in skeletal muscle or adipose tissue could explain improvements in glucose and lipid homeostasis after weight loss.

Design: Volunteers consumed a New Nordic Diet (NND) or an Average Danish Diet (ADD) for 26 weeks in a controlled, free-living setting.

Subjects: 64 moderately obese women and men (44±2 years and BMI 31±1 kg·m(2)).

Intervention: Fasting blood samples and biopsies from the vastus lateralis muscle and subcutaneous abdominal adipose tissue (SCAT) were obtained at week 0 and 26.

Outcome: Gene and protein expressions were analysed by real time PCR and western blotting.

Results: Improved HOMA-IR index and lowered plasma triacylglycerol concentration after NND coincided with molecular adaptations in SCAT, but not in skeletal muscle. NND induced greater reduction in fat mass than ADD (-6±1 kg and -2±1 kg, p<0.01). In SCAT this was associated with increased AMPK and ACC phosphorylation (p<0.05). Concomitantly, NND induced upregulation of Akt2 and AS160 (p<0.05), as well as FATP4 and FABPpm (p<0.05). Indices of increased oxidative capacity were observed, as CPT1 mRNA (p=0.08) as well as CS (p=0.1) and cytochrome C (p=0.05) protein tended to increase.

Conclusion: NND-induced metabolic improvements were accompanied by increased AMPK signalling in SCAT, suggesting a role of AMPK in these adaptations. The concomitant up regulation of key glucose and lipid handling proteins suggests an improved metabolic capacity in adipose tissue after weight loss.