A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning

Molteni, Raffaella; Barnard, R. James; Ying, Zhe; Roberts, Christian K.; Gómez‐Pinilla, Fernando

doi:10.1016/s0306-4522(02)00123-9

Cited by 782 publications

(631 citation statements)

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“…Role m In satiety; m water reward (Horger et al, 1999;Kernie et al, 2000;Nakagawa et al, 2003); improvement in glucose metabolism (Tonra et al, 1999;Nakagawa et al, 2000;Ono et al, 2000) m Drug reward (Horger et al, 1999) K BDNF in mesolimbic pathways regulates appetitive behavior (Eisch et al, 2003;Itoh et al, 2004); BDNF within hypothalamus regulates energy balance by enhancing catabolic processes (Xu et al, 2003) K BDNF may play a role in behavioral sensitization to drugs (Guillin et al, 2001) and potentially to palatable food via its dopaminergic and opioidergic (Siuciak et al, 1994;Siuciak et al, 1995) effects Repeated exposure kIn the hippocampus (Molteni et al, 2002;Molteni et al, 2004) m In mesocorticolimbic areas including, hypothalamus (Meredith et al, 2002;Butovsky et al, 2005); m and upregulation of BDNF receptors during withdrawal (Toda et al, 2002;Grimm et al, 2003); incubation of drug craving, accompanied by m in BDNF (Grimm et al, 2003) BDNF gene knockout animals m In food intake and obesity (Lyons et al, 1999;Kernie et al, 2000;Rios et al, 2001;Xu et al, 2003) k Drug reward (Hall et al, 2003;Horger et al, 1999) Orexin m Food intake (Edwards et al, 1999;Harris et al, 2005) Relapse to drug seeking behavior (Harris et al, 2005) Activated by SGAs ( Ibanez-Rojo et al, 1993;Bencherif et al, 2005) are available, though, to extend preclinical palatable food opioid findings to humans. Neuroimaging studies in obese people reported in...…”

Section: Bdnfmentioning

confidence: 99%

“…Furthermore, similarly to methadone-maintained patients (Willenbring et al, 1989;Zador et al, 1996), exaggerated opioidergic activity could enhance hedonic preference (ie, liking) for sweet and fatty foods (Doyle et al, 1993;Pecina and Berridge, 1995;. The consumption of these foods further reduces BDNF efficiency in preventing neuronal death (Molteni et al, 2002) and in regulating reward function (Horger et al, 1999;Kernie et al, 2000;Nakagawa et al, 2003), glucose metabolism (Tonra et al, 1999;Nakagawa et al, 2000;Ono et al, 2000), appetitive behaviors (Eisch et al, 2003;Itoh et al, 2004), and other important homeostatic processes (Xu et al, 2003).…”

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 99%

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Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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Section: Bdnfmentioning

confidence: 99%

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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“…[11][12][13] The latter was correlated with decreased expression of brain derived neurotrophic factor, cyclic AMP-response element-binding protein and the synaptic proteins synapsin, and stargazin. 11 It has been extensively shown that insulin has a pivotal role in hippocampal neuronal function as a metabolic, growth, synaptic, and survival modulator. [17][18][19][20] Additionally, insulin also has a role in enhancing memory and establishing long-term potentiation through several molecular mechanisms that include neurotransmitter release, expression and insertion of receptors at the postsynaptic membrane, and expression of postsynaptic proteins, mainly via the PI3-K/Akt signaling pathway.…”

Section: Introductionmentioning

confidence: 98%

“…[7][8][9][10] Studies performed in animal models of diet-induced obesity and InsRes such as longterm HFFD feeding show a deficient execution in memory and learning tasks. [11][12][13][14][15][16] These cognitive alterations were associated with functional and structural changes in the hippocampus, such as reduced number and complexity of dendritic spines in the CA1 subfield, altered establishment of long-term potentiation and long-term depression, and diminished dentate gyrus (DG) neurogenesis. [11][12][13] The latter was correlated with decreased expression of brain derived neurotrophic factor, cyclic AMP-response element-binding protein and the synaptic proteins synapsin, and stargazin.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14][15][16] These cognitive alterations were associated with functional and structural changes in the hippocampus, such as reduced number and complexity of dendritic spines in the CA1 subfield, altered establishment of long-term potentiation and long-term depression, and diminished dentate gyrus (DG) neurogenesis. [11][12][13] The latter was correlated with decreased expression of brain derived neurotrophic factor, cyclic AMP-response element-binding protein and the synaptic proteins synapsin, and stargazin. 11 It has been extensively shown that insulin has a pivotal role in hippocampal neuronal function as a metabolic, growth, synaptic, and survival modulator.…”

Section: Introductionmentioning

confidence: 99%

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Short-Term High-Fat-and-Fructose Feeding Produces Insulin Signaling Alterations Accompanied by Neurite and Synaptic Reduction and Astroglial Activation in the Rat Hippocampus

Calvo-Ochoa

Hernández‐Ortega

Ferrera

et al. 2014

J Cereb Blood Flow Metab

128

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Chronic consumption of high-fat-and-fructose diets (HFFD) is associated with the development of insulin resistance (InsRes) and obesity. Systemic insulin resistance resulting from long-term HFFD feeding has detrimental consequences on cognitive performance, neurogenesis, and long-term potentiation establishment, accompanied by neuronal alterations in the hippocampus. However, diet-induced hippocampal InsRes has not been reported. Therefore, we investigated whether short-term HFFD feeding produced hippocampal insulin signaling alterations associated with neuronal changes in the hippocampus. Rats were fed with a control diet or an HFFD consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water. Our results show that 7 days of HFFD feeding induce obesity and InsRes, associated with the following alterations in the hippocampus: (1) a decreased insulin signaling; (2) a decreased hippocampal weight; (3) a reduction in dendritic arborization in CA1 and microtubule-associated protein 2 (MAP-2) levels; (4) a decreased dendritic spine number in CA1 and synaptophysin content, along with an increase in tau phosphorylation; and finally, (5) an increase in reactive astrocyte associated with microglial changes. To our knowledge, this is the first report addressing hippocampal insulin signaling, as well as morphologic, structural, and functional modifications due to short-term HFFD feeding in the rat.

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Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function

Brinkworth

Buckley

Noakes³

et al. 2009

Arch Intern Med

169

133

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A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning

Cited by 782 publications

References 50 publications

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Short-Term High-Fat-and-Fructose Feeding Produces Insulin Signaling Alterations Accompanied by Neurite and Synaptic Reduction and Astroglial Activation in the Rat Hippocampus

Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function

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