The ketogenic diet does not alter brain expression of orexigenic neuropeptides

Tabb, Kroshona D; Szot, Patricia; White, Sylvia S.; Liles, L. Cameron

doi:10.1016/j.eplepsyres.2004.08.002

Cited by 18 publications

(14 citation statements)

References 17 publications

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“…3E1,E2). The latter two brain regions contain dense dendritic processes expressing high levels of NPY (Chronwall et al, 1985;Tabb et al, 2004). NeuN immunofluorescence, shown in red, was detected in nuclei and cell bodies and its intensity did not vary significantly between tissue from OA-and VPA-treated animals.…”

Section: Resultsmentioning

confidence: 95%

Chronic Valproic Acid Treatment Triggers Increased Neuropeptide Y Expression and Signaling in Rat Nucleus Reticularis Thalami

Brill

Lee

Zhao

et al. 2006

Journal of Neuroscience

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Section: Resultsmentioning

confidence: 95%

Chronic Valproic Acid Treatment Triggers Increased Neuropeptide Y Expression and Signaling in Rat Nucleus Reticularis Thalami

Brill

Lee

Zhao

et al. 2006

Journal of Neuroscience

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“…For example, the increased cortisol levels we found in rats on the KD mirrors the increase seen in children on the KD and may contribute to the anticonvulsant effect of the diet (33). Others have considered the possibility that changes in neuropeptide Y and galanin expression contribute to the effects of the KD, but the diet does not change their brain mRNA levels (34). Rather than excluding a contribution of other neurohormones, our results indicate that studying KD-induced changes in neurohormones involved in energy homeostasis may help elucidate the mechanisms underlying the anticonvulsant and weight effects of the KD.…”

Section: Discussionmentioning

confidence: 95%

Leptin Contributes to Slower Weight Gain in Juvenile Rodents on a Ketogenic Diet

et al. 2006

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ABSTRACT:The ketogenic diet (KD) is an efficacious therapy for medically refractory childhood epilepsy that also slows weight gain. We tested the hypothesis that the KD slows weight gain via neurohormones involved in energy homeostasis. We found that juvenile rodents fed a KD had slower weight gain than those fed a standard diet (SD). Rats fed a KD had higher serum leptin levels and lower insulin levels compared with those fed an SD. We investigated the increase in leptin further because this change was the only one consistent with slower weight gain. Although rats fed the SD experienced slower weight gain when calorie restricted, they had serum leptin levels similar to those fed the SD ad libitum. Furthermore, leptin deficient (ob/ob) and leptin receptor deficient (db/db) mice did not show slower weight gain on the KD. All animals on the KD had elevated serum ␤-hydroxybutyrate (␤HB) levels. Thus, ketosis is insufficient and a functioning leptin signaling system appears necessary for the KD to slow weight gain. The increase in leptin may contribute to the anticonvulsant effects of the KD. F ew treatment options exist for the 20 -30% of epileptic children whose seizures are refractory to medication. One option is the KD, a high-fat, low-carbohydrate, and adequate protein diet. The KD is remarkably effective in children with medically refractory epilepsy as 5-10% become seizure free and 30% have a Ͼ90% reduction in seizure frequency (1). Yet, its adverse effects and the parental effort involved in implementing and maintaining the diet limit its use. Thus, all epileptic children would benefit from a simpler method of attaining the diet's anticonvulsant effects, which requires elucidating its mechanism of action.Here we focus on what the impaired weight gain associated with the KD might reveal about the diet's anticonvulsant mechanism. Several studies report that children on the KD drop about 10 percentiles in weight, although appropriate weight gain is the goal (2,3). Recognizing that lowcarbohydrate diets, such as the Atkins diet, are ketogenic makes this impaired weight gain less surprising. Indeed, the Atkins diet and other low-carbohydrate KDs result in a 5% to 10% weight loss over 6 mo (4,5). Furthermore, rodents placed on a KD show slower weight gain (6,7).We hypothesized that the anticonvulsant and weight effects of the KD share a common mechanism involving a change in the serum levels of leptin, insulin, ghrelin, or cortisol. These peripherally released hormones help determine body weight because they regulate energy homeostasis (8). Importantly, leptin and insulin also modulate neuronal excitability (9,10). METHODSDietary protocols. Experimental protocols were approved by the Washington University Animal Studies Committee. Sprague-Dawley rats (Charles River Laboratories, Wilmington, MA), male ob/ob mice (Stock 000632, The Jackson Laboratory, Bar Harbor, ME), male C57BL/6J mice (Stock 000664, The Jackson Laboratory), male db/db mice (Stock 000642, The Jackson Laboratory), and male C57BLKS/J mice (Stock 0006...

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“…It has been suggested that anticonvulsant neuropeptides involved in fat metabolism could have a role in the efficacy of the ketogenic diet [66], but the diet does not change galanin or neuropeptide Y levels [67].…”

Section: Role Of Norepinephrine and Peptidergic Neurotransmitter Systemsmentioning

confidence: 99%

The Neuropharmacology of the Ketogenic Diet

Hartman

Gąsior

Vining

et al. 2007

Pediatric Neurology

280

169

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The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone bodies partly replacing glucose as fuel. Whether these metabolic changes contribute to acute seizure protection is unclear; however, the ketone body acetone has anticonvulsant activity and could play a role in the seizure protection afforded by the diet. In addition to acute seizure protection, the ketogenic diet provides protection against the development of spontaneous recurrent seizures in models of chronic epilepsy, and it has neuroprotective properties in diverse models of neurodegenerative disease.

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The ketogenic diet does not alter brain expression of orexigenic neuropeptides

Cited by 18 publications

References 17 publications

Chronic Valproic Acid Treatment Triggers Increased Neuropeptide Y Expression and Signaling in Rat Nucleus Reticularis Thalami

Chronic Valproic Acid Treatment Triggers Increased Neuropeptide Y Expression and Signaling in Rat Nucleus Reticularis Thalami

Leptin Contributes to Slower Weight Gain in Juvenile Rodents on a Ketogenic Diet

The Neuropharmacology of the Ketogenic Diet

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