PPAR mRNA Levels Are Modified by Dietary n-3 Fatty Acid Restriction and Energy Restriction in the Brain and Liver of Growing Rats

J Nutr. 2017 Feb;147(2):161-169. doi: 10.3945/jn.116.237107. Epub 2016 Dec 7.


Background: Without dietary sources of n-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs), α-linolenic acid (ALA; 18:3n-3) is the precursor for docosahexaenoic acid (DHA; 22:6n-3). It is not known how energy restriction (ER) affects ALA conversion to DHA.

Objective: We tested the hypothesis that ER reduces n-3 LCPUFA concentrations in tissues of growing rats fed diets replete with and deficient in ALA.

Methods: Male Sprague-Dawley rats (23 d old) were provided AIN93G diets (4 wk) made with soybean oil (SO; ALA sufficient) or corn oil (CO; ALA deficient) providing 16% of energy as fat. For each dietary oil, ER rats were individually pair-fed 75% of another rat's ad libitum (AL) intake. Fatty acid (FA) concentrations in brain regions, liver, and plasma were analyzed. Expression of peroxisome proliferator-activated receptors (PPARs), uncoupling proteins (UCPs), and mitochondrial DNA was analyzed in the brain and liver.

Results: AL rats consuming CO had a 65% lower concentration of n-3 docosapentaenoic acid (22:5n-3) and a 10% lower DHA concentration in the cerebral cortex and cerebellum than did the SO-AL group. ER did not alter cerebral n-3 LCPUFA status. Liver n-3 LCPUFA concentrations were reduced in rats fed CO compared with SO. ER reduced hepatic linoleic acid (18:2n-6), ALA, and arachidonic acid (20:4n-6) regardless of oil. ER and n-3 FA deficiency had independent effects on the mRNA levels of Pparα, Pparβ/δ, and Pparγ in the liver, cerebral cortex, and cerebellum. ER reduced Ucp3 mRNA by nearly 50% in the cerebral cortex, cerebellum, and liver, and Ucp5 mRNA was 30% lower in the cerebellum of rats receiving the CO diet.

Conclusions: Small perturbations in PUFA concentration and ER modify the mRNA levels of Ppar and Ucp in the juvenile rat brain. More research is needed to identify the long-term physiologic and behavioral impacts of ER and PUFA restriction in the juvenile brain.

Keywords: PPAR; brain; energy restriction; uncoupling proteins; α-linolenic acid.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animal Feed / analysis
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Brain / metabolism*
  • Caloric Restriction
  • Diet
  • Fatty Acids, Omega-3 / administration & dosage*
  • Gene Expression Regulation, Developmental / physiology*
  • Liver / metabolism*
  • Male
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Fatty Acids, Omega-3
  • Peroxisome Proliferator-Activated Receptors
  • RNA, Messenger