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

Xihong Zhou,Weiche Wu,Yizhen Wang,Xinxia Wang,Jingqing Chen

doi:10.1186/s12986-015-0006-5

Xihong Zhou, Weiche Wu + Show 3 more

Open Access

https://doi.org/10.1186/s12986-015-0006-5

Copy DOI

Abstract

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.

Highlights

Many studies have demonstrated that n-3 long chain polyunsaturated fatty acid (n-3 LC Long Chain Polyunsaturated Fatty Acid (PUFA)) could reduce adiposity by improving the dysfunctional lipid metabolism induced by high-fat diet (HFD), such as stimulation of lipolysis and inhibition of lipogenesis in liver [1,2], as well as stimulation of fatty acid oxidation in muscle [3]
Dietary alpha-linolenic acid (ALA) significantly decreased epididymal fat accumulation and increased DNA copies in WT mice with HFD, while such effects were not observed in AMPKα1−/− and AMPKα2−/− mice
Our results showed that cell size of both epididymal and inguinal adipocytes in mice of all genotypes tended to be decreased after ALA supplementation (Figure 1)

Summary

Introduction

Many studies have demonstrated that n-3 long chain polyunsaturated fatty acid (n-3 LC PUFA) could reduce adiposity by improving the dysfunctional lipid metabolism induced by HFD, such as stimulation of lipolysis and inhibition of lipogenesis in liver [1,2], as well as stimulation of fatty acid oxidation in muscle [3]. N-3 PUFA exerts these effects by upregulating mitochondrial biogenesis and increasing β-oxidation [6], and by reducing cellularity of white adipose tissue [7]. Other studies report that long chain fatty acids could regulate carnitine palmitoyltranferase I (CPT1a), which is the rate-limiting enzyme in mitochondrial fatty acid oxidation in a PPARα-independent manner

Methods

Results

Discussion

Conclusion