Safflower (n-6) and flaxseed (n-3) high-fat diets differentially regulate hypothalamic fatty acid profiles, gene expression, and insulin signalling

Maria Fernanda Fernandes; Maria Cristina Tache; Shannon L Klingel; Francesco Leri; David M Mutch

doi:10.1016/j.plefa.2017.12.002

Safflower (n-6) and flaxseed (n-3) high-fat diets differentially regulate hypothalamic fatty acid profiles, gene expression, and insulin signalling

Prostaglandins Leukot Essent Fatty Acids. 2018 Jan:128:67-73. doi: 10.1016/j.plefa.2017.12.002. Epub 2017 Dec 8.

Authors

Maria Fernanda Fernandes¹, Maria Cristina Tache², Shannon L Klingel², Francesco Leri³, David M Mutch⁴

Affiliations

¹ Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1; Department of Psychology, University of Guelph, Guelph, ON, Canada, N1G 2W1.
² Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1.
³ Department of Psychology, University of Guelph, Guelph, ON, Canada, N1G 2W1.
⁴ Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1. Electronic address: dmutch@uoguelph.ca.

PMID: 29413363
DOI: 10.1016/j.plefa.2017.12.002

Abstract

Polyunsaturated fatty acids (PUFA) have important signalling roles in the hypothalamus, a region of the brain that regulates whole-body energy homeostasis. While evidence suggests that high PUFA intake can impact hypothalamic activity, the underlying molecular mechanisms regulated by essential dietary n-6 and n-3 PUFA (i.e., linoleic acid and α-linolenic acid, respectively) remain poorly described in this brain region. To differentiate the roles of essential dietary PUFA on hypothalamic function, we fed male rats high-fat diets (35% kcal/d) containing either safflower (linoleic acid) or flaxseed (α-linolenic acid) oil for 2 months. Control rats were fed a low-fat (16% kcal/d) diet containing soybean oil. Hypothalamic fatty acids and gene expression were investigated by gas chromatography and microarray, respectively. Safflower-fed rats had higher total n-6 PUFA content due to increases in linoleic acid, arachidonic acid, and osbond acid compared to the other diet groups, while flaxseed-fed rats had higher total n-3 content due to increases in α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. Safflower-fed rats showed augmented expression of genes related to hypothalamic insulin signalling compared to controls. This was mirrored by significant increases in phosphorylated AKT^thr308 and AKT^ser473 levels; indicative of increased PI(3)K/AKT pathway activity. These changes were not observed in the hypothalamus of flaxseed-fed rats. Our findings provide new molecular insights into how essential fatty acids influence the hypothalamus and, potentially, whole-body energy homeostasis. This work also provides new knowledge to better understand the impact of essential fatty acids on metabolic and behavioral phenotypes.

Keywords: Alpha-linolenic acid; Gas chromatography; High-fat diet; Hypothalamus; Linoleic acid; Microarray.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diet, High-Fat
Fatty Acids / metabolism
Fatty Acids, Omega-3 / pharmacology
Fatty Acids, Omega-6 / pharmacology
Gene Expression Regulation / drug effects*
Hypothalamus / drug effects*
Hypothalamus / physiology
Insulin / metabolism*
Linseed Oil / chemistry
Linseed Oil / pharmacology*
Male
Rats, Sprague-Dawley
Safflower Oil / chemistry
Safflower Oil / pharmacology*

Substances

Fatty Acids
Fatty Acids, Omega-3
Fatty Acids, Omega-6
Insulin
Safflower Oil
Linseed Oil