Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals.
Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with that of canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergic systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol, serotonin (5-HT) (P<.056), dopamine, neuropeptide Y (NPY) and Ca(2+)/calmodulin (CaM)-dependent protein kinase (Camkk2). In the hippocampus, fish oil supplementation normalized 5-HT, Camkk2, silent mating type information regulation 1 and brain-derived neurotrophic factor. In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems.
Department of Human Nutrition and Metabolism and School of Public Health, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel. yosefa@md.huji.ac.il
Yosefa
Y
Avraham
Mayer
M
Saidian
James J
JJ
Burston
Raphael
R
Mevorach
Lia
L
Vorobiev
Iddo
I
Magen
Eithan
E
Kunkes
Beatriz
B
Borges
Aron H
AH
Lichtman
Elliot M
EM
Berry
D000818:Animals; D001835:Body Weight; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy*; D004298:Dopamine / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D015870:Gene Expression; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D044342:Malnutrition / Q000188:drug therapy*; D051379:Mice; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000074262:Rapeseed Oil; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D012527:Satiation / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D005229:Fatty Acids, Monounsaturated; D005395:Fish Oils; D009478:Neuropeptide Y; D000074262:Rapeseed Oil; D043884:Receptor, Cannabinoid, CB1; D044263:Receptors, Serotonin, 5-HT1; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C517700:Camkk2 protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D004298:Dopamine