Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

Nutrients. 2017 Oct 19;9(10):1145. doi: 10.3390/nu9101145.


Metallothioneins (MTs) perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER) and dietary n-3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n-3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO) that is α-linolenic acid (ALA; 18:3n-3) sufficient or corn oil (CO; ALA-deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs (Mt1-3) and modulators of MT expression including glucocorticoid receptors (Nr3c1 and Nr3c2) and several mediators of thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb) were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral cortex (23%). In liver, a reduction in dietary n-3 PUFA reduced Mt1, Mt2, Nr3c1, Mct8, and Thrb. ER elevated Nr3c1, Dio1, and Thrb and reduced Thra in the liver. Given MT's role in cellular protection, further studies are needed to evaluate whether ER or n-3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors.

Keywords: brain development; cerebellum; energy restriction; juvenile; mRNA; metallothionein; n-3 PUFA.

MeSH terms

  • Animals
  • Body Composition
  • Brain / metabolism*
  • Caloric Restriction*
  • Copper / metabolism
  • Corn Oil / administration & dosage
  • Corticosterone / blood
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / blood
  • Fatty Acids, Omega-3 / deficiency*
  • Fatty Acids, Omega-6 / administration & dosage
  • Fatty Acids, Omega-6 / blood
  • Gene Expression Regulation
  • Liver / metabolism*
  • Male
  • Malnutrition / blood
  • Malnutrition / diagnosis
  • Malnutrition / diet therapy
  • Manganese / metabolism
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Soybean Oil / administration & dosage
  • Triiodothyronine / blood
  • Zinc / metabolism
  • alpha-Linolenic Acid / administration & dosage


  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Monocarboxylic Acid Transporters
  • Mt2A protein, rat
  • NR3C1 protein, rat
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • monocarboxylate transporter 8, rat
  • Triiodothyronine
  • alpha-Linolenic Acid
  • Manganese
  • Copper
  • Soybean Oil
  • Corn Oil
  • Metallothionein
  • Zinc
  • Corticosterone