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

backgroundn-3 long chain polyunsaturated fatty acid (n-3 LC PUFA) increases β-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.

methodsAMPKα1(-/-), AMPKα2(-/-) 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.

resultsOur 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 [PGC1α] and nuclear respiratory factor-1 [nrf1]) and β-oxidation related genes (carnitine palmitoyltransferase 1A [CPT1a] and peroxisome proliferator-activated receptor alpha [PPARα]) 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 AMPKα1 and AMPKα2 knockout mice.

conclusionsOur results suggest that ALA could improve adipose tissue function and its anti-adipogenic effects are dependent on AMPK.