AMP-activated protein kinase is required for the anti-adipogenic effects of alpha-linolenic acid

Background: n-3 long chain polyunsaturated fatty acid (n-3 LC PUFA) increases beta-oxidation and limits lipid accumulation in adipocytes. The current study was conducted to determine whether their precursor alpha-linolenic acid (ALA) could also exert the above effects and how AMP-activated protein kinase (AMPK) was involved. Methods: AMPK alpha 1(-/-), AMPK alpha 2(-/-) mice and wild-type (WT) mice were fed a high-fat diet (HFD) or HFD with ALA. Body weight was recorded weekly and serum was collected. Adipocytes size and expression of key players involved in mitochondrial biogenesis and lipid oxidation were also measured. Results: Our results showed an elevated serum adiponectin level and a decreased leptin and insulin level in WT mice fed HFD with ALA when compared with WT mice fed HFD. In addition, dietary ALA decreased epididymal adiposity and adipocytes size in WT mice. At protein level, mitochondrial genes (peroxisome proliferator-activated receptor gamma coactivator 1 alpha [PGC1 alpha] and nuclear respiratory factor-1 [nrf1]) and beta-oxidation related genes (carnitine palmitoyltransferase 1A [CPT1 alpha] and peroxisome proliferator-activated receptor alpha [PPAR alpha]) were upregulated by dietary ALA in epididymal fat of WT mice. Consistently, dietary ALA also increased mitochondrial genomic DNA copy numbers. Moreover, lipogenesis was repressed by dietary ALA, indicated by that expression of fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and stearoyl-CoA desaturase 1 (SCD1) were decreased. However, these aforementioned effects were abolished in the AMPK alpha 1 and AMPK alpha 2 knockout mice. Conclusions: Our results suggest that ALA could improve adipose tissue function and its anti-adipogenic effects are dependent on AMPK.