Fatty Acid Status and Its Relationship to Cognitive Decline and Homocysteine Levels in the Elderly

Baierle, Marília; Vencato, Patrícia Heuser; Oldenburg, Luiza; Bordignon, Suelen; Zibetti, Murilo Ricardo; Trentini, Clarissa M.; Duarte, Marta Maria Medeiros Frescura; Veit, Juliana Cristina; Somacal, Sabrina; Emanuelli, Tatiana; Grune, Tilman; Breusing, Nicolle; Garcia, Solange Cristina

doi:10.3390/nu6093624

Cited by 38 publications

(30 citation statements)

References 47 publications

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“…A multitude of epidemiological studies have suggested that a diet rich in saturated free fatty acids (sFFA) adversely affects cognition [18, 19] and is closely associated with cognitive decline [20]. Also, the degree of saturated fat or saturated fatty acid intake in diet commensurately dictates the degree and extent of cognitive decline [21].…”

Section: Introductionmentioning

confidence: 99%

Palmitate-induced Endoplasmic Reticulum stress and subsequent C/EBPα Homologous Protein activation attenuates leptin and Insulin-like growth factor 1 expression in the brain

Marwarha

Claycombe

Schommer

et al. 2016

Cellular Signalling

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The peptide hormones insulin-like growth factor-1 (IGF1) and leptin mediate a myriad of biological effects - both in the peripheral and central nervous systems. The transcription of these two hormones is regulated by the transcription factor C/EBPα, which in turn is negatively regulated by the transcription factor C/EBP Homologous Protein (CHOP), a specific marker of endoplasmic reticulum (ER) stress. In the peripheral system, disturbances in leptin and IGF-1 levels are implicated in a variety of metabolic diseases including obesity, diabetes, atherosclerosis and cardiovascular diseases. Current research suggests a positive correlation between consumption of diets rich in saturated free fatty acids (sFFA) and metabolic diseases. Induction of ER stress and subsequent dysregulation in the expression levels of leptin and IGF-1 have been shown to mediate sFFA-induced metabolic diseases in the peripheral system. Palmitic acid (palmitate), the most commonly consumed sFFA, has been shown to be up-taken by the brain, where it may promote neurodegeneration. However, the extent to which palmitate induces ER stress in the brain and attenuates leptin and IGF1 expression has not been determined. We fed C57BL/6J mice a palmitate-enriched diet and determined effects on the expression levels of leptin and IGF1 in the hippocampus and cortex. We further determined the extent to which ER stress and subsequent CHOP activation mediate the palmitate effects on the transcription of leptin and IGF1. We demonstrate that palmitate induces ER stress and decreases leptin and IGF1 expression by inducing the expression of CHOP. The molecular chaperone 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress, precludes the palmitate-evoked down-regulation of leptin and IGF1 expression. Furthermore, the activation of CHOP in response to ER stress is pivotal in the attenuation of leptin and IGF1 expression as knocking-down CHOP in mice or in SH-SY5Y and Neuro-2a (N2a) cells rescues the palmitate-induced mitigation in leptin and IGF1 expression. Our study implicates for the first time ER stress-induced CHOP activation in the brain as a mechanistic link in the palmitate-induced negative regulation of leptin and IGF1, two neurotrophic cytokines that play an indispensable role in the mammalian brain.

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Section: Introductionmentioning

confidence: 99%

Palmitate-induced Endoplasmic Reticulum stress and subsequent C/EBPα Homologous Protein activation attenuates leptin and Insulin-like growth factor 1 expression in the brain

Marwarha

Claycombe

Schommer

et al. 2016

Cellular Signalling

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“…[39] [40] [41]. Moreover the brain has high energy requirements, since this cerebral orange represents only 2% of the total body mass, consumes 20% of the oxygen and 25% of the glucose consumed by the total human body[42].The brain is a complex organ with high metabolism which by aging becomes more vulnerable to oxidative stress.…”

mentioning

confidence: 99%

Association between Malnutrition and Cognitive Impairment among Morocco’s Older Adults

Talhaoui¹,

Aboussaleh²,

Ahami³

et al. 2019

OJMP

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Objective: The aim of this study was to determine the association between the malnutrition and risk of cognitive impairment among Morocco older adults. Materials and methods: A sample of 237 older adults aged above 60 years were recruited from three nursing homes belonging to three different cities, Rabat, Kenitra and Sidi Kacem City and from one health center in Sidi Kacem City. From them, 172 subjects (56.4% men) were included in our study for their completion. Cognitive functions were assessed by the Mini-Mental State Examination. Nutritional status, depression and physical activity were assessed using respectively: MNA, GDS-15 and GPAQ. The binary logistic regression was performed where the cognitive function was taking as the dependent variable and all other outcomes as independent variables. Results: Our results showed that 69.8% of total simple were classed as having cognitive impairment while only 30.2% were normal. The binary logistic regression assessed showed that the malnutrition (OR = 3.03, 95% CI: 1.34-6.85), gender (OR = 2.22, 95% CI: 1.03-5.71) and low education (OR = 8.35, 95% CI: 1.32-52.83) were risk factors for cognitive impairment, when moderate level of physical activity (OR = 0.19, 95% CI: 0.06-0.54) was a protective factor compared to the limited level. Conclusions: Our study supported past literature that malnutrition and low level of physical activity were risk factors of cognitive impairment. These indicate that nutritional status monitoring and the practice of regular physical activities can prevent it from leading to Alzheimer's disease.

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“…In 2014, an observational case-control study by Baierle and colleagues enrolling 12 elderly patients with cognitive decline according to the mini-mental state examination (MMSE) performance test, showed lower levels of serum DHA and total n-3 PUFAs compared to 33 control patients with normal MMSE scores [83]. Cognitive functions were positively associated with DHA and total n-3 PUFAs levels.…”

Section: Latest Insight and Implications For Cognitive Performance Anmentioning

confidence: 99%

The Link between Homocysteine and Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future Directions

Rizzo¹,

Laganà

2020

Biomolecules

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Omega-3 polyunsaturated fatty acids and B vitamins are linked to metabolic and degenerative disorders, such as cardiovascular disease and cognitive decline. In the last two decades, the interplay between B vitamins and omega-3 polyunsaturated fatty acids gained increasing attention. Expression control on enzymes involved in the pathway of homocysteine by polyunsaturated fatty acids has been proposed. The methylation process seems crucial for the metabolism of polyunsaturated fatty acids and their distribution within the body. This review summarizes the available data in humans about the link between homocysteine and omega-3 polyunsaturated fatty acids, with a special focus on the meta-analyses of randomized clinical trials. Even if the paucity of available information about the topic does not allow for definitive conclusions, a synergic action between polyunsaturated fatty acids and B vitamins may play a key role in regulating several metabolic pathways. This element could explain a stronger action on homocysteine levels when omega-3 polyunsaturated fatty acids and B vitamins are supplemented simultaneously. To date, a robust rationale of intervention to prevent metabolic diseases is lacking and could be beneficial for individual health and healthcare policy.

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Fatty Acid Status and Its Relationship to Cognitive Decline and Homocysteine Levels in the Elderly

Cited by 38 publications

References 47 publications

Palmitate-induced Endoplasmic Reticulum stress and subsequent C/EBPα Homologous Protein activation attenuates leptin and Insulin-like growth factor 1 expression in the brain

Palmitate-induced Endoplasmic Reticulum stress and subsequent C/EBPα Homologous Protein activation attenuates leptin and Insulin-like growth factor 1 expression in the brain

Association between Malnutrition and Cognitive Impairment among Morocco’s Older Adults

The Link between Homocysteine and Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future Directions

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