Extra virgin olive oil intake delays the development of amyotrophic lateral sclerosis associated with reduced reticulum stress and autophagy in muscle of SOD1G93A mice

J Nutr Biochem. 2014 Aug;25(8):885-92. doi: 10.1016/j.jnutbio.2014.04.005. Epub 2014 May 2.


Amyotrophic lateral sclerosis is a neurodegenerative disease associated with mutations in antioxidant enzyme Cu/Zn-superoxide dismutase 1. Albeit there is no treatment for this disease, new insights related to an exacerbated lipid metabolism have been reported. In connection with the hypermetabolic lipid status, the hypothesis whether nature of dietary fat might delay the progression of the disease was tested by using a transgenic mouse that overexpresses the human SOD1G93A variant. For this purpose, SOD1G93A mice were assigned randomly to one of the following three experimental groups: (1) a standard chow diet (control, n=21), (2) a chow diet enriched with 20% (w/w) extra virgin olive oil (EVOO, n=22) and (3) a chow diet containing 20% palm oil (palm, n=20). They received the diets for 8 weeks and the progression of the disease was assessed. On the standard chow diet, average plasma cholesterol levels were lower than those mice receiving the high-fat diets. Mice fed an EVOO diet showed a significant higher survival and better motor performance than control mice. EVOO group mice survived longer and showed better motor performance and larger muscle fiber area than animals receiving palm. Moreover, the EVOO-enriched diet improved the muscle status as shown by expression of myogenic factors (Myod1 and Myog) and autophagy markers (LC3 and Beclin1), as well as diminished endoplasmic reticulum (ER) stress through decreasing Atf6 and Grp78. Our results demonstrate that EVOO may be effective in increasing survival rate, improving motor coordination together with a potential amelioration of ER stress, autophagy and muscle damage.

Keywords: Amyotrophic lateral sclerosis; Autophagy; Cu/Zn-superoxide dismutase 1; Extra virgin olive oil; Palm oil; Reticulum stress; SOD1G93A mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6 / metabolism
  • Amyotrophic Lateral Sclerosis / etiology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Amyotrophic Lateral Sclerosis / prevention & control*
  • Animals
  • Autophagy / drug effects*
  • Cholesterol / metabolism
  • Endoplasmic Reticulum Stress / drug effects
  • Female
  • Heat-Shock Proteins / metabolism
  • Longevity / drug effects
  • Male
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Muscle Fibers, Skeletal / drug effects
  • Olive Oil
  • Palm Oil
  • Plant Oils / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1


  • Activating Transcription Factor 6
  • Atf6 protein, mouse
  • Heat-Shock Proteins
  • Olive Oil
  • Plant Oils
  • Reactive Oxygen Species
  • SOD1 protein, human
  • Palm Oil
  • Cholesterol
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • molecular chaperone GRP78