Elsevier

Molecular Metabolism

Volume 5, Issue 8, August 2016, Pages 680-689
Molecular Metabolism

Original article
Sexually dimorphic brain fatty acid composition in low and high fat diet-fed mice

https://doi.org/10.1016/j.molmet.2016.06.014Get rights and content
Under a Creative Commons license
open access

Highlights

  • There is a sexual dimorphism in brain lipid composition.

  • Brains of male mice following high fat diet exposure are enriched in saturated fatty acids.

  • Male brains are depleted of polyunsaturated fatty acids following high fat diet exposure.

  • Linoleic acid inhibits palmitic acid-induced inflammation in hypothalamic cells.

Abstract

Objective

In this study, we analyzed the fatty acid profile of brains and plasma from male and female mice fed chow or a western-style high fat diet (WD) for 16 weeks to determine if males and females process fatty acids differently. Based on the differences in fatty acids observed in vivo, we performed in vitro experiments on N43 hypothalamic neuronal cells to begin to elucidate how the fatty acid milieu may impact brain inflammation.

Methods

Using a comprehensive mass spectrometry fatty acid analysis, which includes a profile for 52 different fatty acid isomers, we assayed the plasma and brain fatty acid composition of age-matched male and female mice maintained on chow or a WD. Additionally, using the same techniques, we determined the fatty acid composition of N43 hypothalamic cells following exposure to palmitic and linoleic acid, alone or in combination.

Results

Our data demonstrate there is a sexual dimorphism in brain fatty acid content both following the consumption of the chow diet, as well as the WD, with males having an increased percentage of saturated fatty acids and reductions in ω6-polyunsaturated fatty acids when compared to females. Interestingly, we did not observe a sexual dimorphism in fatty acid content in the plasma of the same mice. Furthermore, exposure of N43 cells to the ω6-PUFA linoleic acid, which is higher in female brains when compared to males, reduces palmitic acid-induced inflammation.

Conclusions

Our data suggest male and female brains, and not plasma, differ in their fatty acid profile. This is the first time, to our knowledge, lipidomic analyses has been used to directly test the hypothesis there is a sexual dimorphism in brain and plasma fatty acid composition following consumption of the chow diet, as well as following exposure to the WD.

Keywords

Obesity
N43
Palmitic acid
Linoleic acid
Central nervous system
Western diet
ω6-fatty acids

Abbreviations

AA
arachidonic acid
ACC
acetyl-CoA carboxylase
B2m
beta-2 microglobulin
BBB
blood brain barrier
BSA
bovine serum albumin
C
Chow diet
CNS
central nervous system
DHA
docosahexaenoic acid
F
female
FAs
fatty acids
FABP
fatty acid binding protein
FAT/CD36
fatty acid transporter
FATP1
fatty acid transport protein 1
FAS
fatty acid synthase
FFAs
free fatty acids
IL6
interleukin 6
LA
linoleic acid
M
male
MCD
malonyl-CoA decarboxylase
MSFD2a
membrane protein major facilitator super family domain containing 2a
MUFAs
monounsaturated fatty acids
NF-κB
Nuclear Factor-κ Beta
PA
palmitic acid
PUFAs
polyunsaturated fatty acids
SatFAs
saturated fatty acids
TFAs
total fatty acids
TNFα
Tumor Necrosis Factor α
UnsatFAs
unsaturated fatty acids
WD
western diet
WT
wild-type

Cited by (0)

4

Eugenia Morselli and Deborah Clegg share senior authorship.