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      Chronic Consumption of Fructose Induces Behavioral Alterations by Increasing Orexin and Dopamine Levels in the Rat Brain

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          Abstract

          It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep–wake cycle, locomotion, and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep–wake cycle of rats, increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons, which may be responsible for alterations of the sleep–wake cycle.

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          Most cited references49

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          Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

          Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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            National estimates of dietary fructose intake increased from 1977 to 2004 in the United States.

            Our purpose was to conduct a new analysis to update and extend previously published trends of fructose availability and estimated fructose intake and food sources of dietary fructose from the 1977-1978 Nationwide Food Consumption Survey (NFCS) data. We estimated fructose usual intake with data from NHANES 1999-2004 for 25,165 individuals (1 y and older, excluding pregnant and lactating women and breast-fed infants) using the Iowa State C-SIDE software. We applied food group-specific conversion factors to individual measures of sugar intakes following the earlier study. Sweetener availability in the United States increased from 1978, peaked in 1999, and declined through 2005. The high-fructose corn syrup percentage of sweeteners increased from 16% in 1978 to 42% in 1998 and then stabilized. Since 1978, mean daily intakes of added and total fructose increased in all gender and age groups, whereas naturally occurring (N) fructose intake decreased or remained constant. Total fructose intake as percentage of energy and as percentage of carbohydrate increased 1 and 1.2%, whereas daily energy and carbohydrate intakes increased 18 and 41%, respectively. Similar to 1978 results, nonalcoholic beverages and grain products were the principal food sources of added fructose. Fruits and fruit products were the main dietary sources of N fructose in 2004; in 1978, grain products and vegetables were more predominant food sources. Although comparison of estimates of fructose intakes between data from the 1977-1978 NFCS and the NHANES 1999-2004 showed an increase, this increase was dwarfed by greater increases in total daily energy and carbohydrate intakes.
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              Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome.

              As dietary exposure to fructose has increased over the past 40 years, there is growing concern that high fructose consumption in humans may be in part responsible for the rising incidence of obesity worldwide. Obesity is associated with a host of metabolic challenges, collectively termed the metabolic syndrome. Fructose is a highly lipogenic sugar that has profound metabolic effects in the liver and has been associated with many of the components of the metabolic syndrome (insulin resistance, elevated waist circumference, dyslipidemia, and hypertension). Recent evidence has also uncovered effects of fructose in other tissues, including adipose tissue, the brain, and the gastrointestinal system, that may provide new insight into the metabolic consequences of high-fructose diets. Fructose feeding has now been shown to alter gene expression patterns (such as peroxisome proliferator-activated receptor-γ coactivator-1α/β in the liver), alter satiety factors in the brain, increase inflammation, reactive oxygen species, and portal endotoxin concentrations via Toll-like receptors, and induce leptin resistance. This review highlights recent findings in fructose feeding studies in both human and animal models with a focus on the molecular and biochemical mechanisms that underlie the development of insulin resistance, hepatic steatosis, and the metabolic syndrome.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 November 2018
                November 2018
                : 10
                : 11
                : 1722
                Affiliations
                [1 ]Laboratorio Fisiología de la Formación Reticular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México 14269, Mexico; joaquinmanjarrez@ 123456hotmail.com (J.M.-M.); adriana.neri@ 123456ciencias.unam.mx (A.N.-S.); normanut2484@ 123456hotmail.com (N.S.-R.)
                [2 ]Laboratorio de Física Medica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México 14269, Mexico; paolabaze@ 123456gmail.com
                [3 ]Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
                [4 ]Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México 14269, Mexico; smontes@ 123456innn.edu.mx
                [5 ]Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México 14269, Mexico; miguelqfbuamx@ 123456gmail.com
                [6 ]Laboratorio Nacional de Microscopía Avanzada, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, Mexico; vadim.perez@ 123456imss.gob.mx
                Author notes
                [* ]Correspondence: jfranco@ 123456innn.edu.mx ; Tel.: +52-555-606-3822
                Author information
                https://orcid.org/0000-0001-9670-8502
                https://orcid.org/0000-0001-9118-8800
                Article
                nutrients-10-01722
                10.3390/nu10111722
                6265759
                30423806
                6c852c4f-6bd4-4b1e-99e3-561bc59f6b51
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 October 2018
                : 08 November 2018
                Categories
                Article

                Nutrition & Dietetics
                fructose,sleep–wake cycle,locomotor activity,dopamine,orexin a,lateral hypothalamic area,ventral tegmental area

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