PXD023070

PXD023070 is an original dataset announced via ProteomeXchange.

Title	Obesity-associated deterioration of the hippocampus is partially restored after weight loss - AWL_ContA
Description	Objective Obesity is a multidimensional condition that is treatable by the restoration of a lean phenotype; however, some obesity-related outcomes may persist after weight normalization. Among the organs of the human body, the brain possesses a relatively low regenerative capacity and could retain perturbations established as a result of developmental obesity. Calorie restriction (CR) or a restricted ketogenic diet (KD) are successfully used as weight loss approaches, but their impact on obesity-related effects in the brain have not been previously evaluated. Methods We performed a series of experiments in a rat model of developmental obesity induced by a 12-week cafeteria diet, followed by CR to implement weight loss. First, we assessed the impact of obesity on neurogenesis (BrdU incorporation into the hippocampus), cognitive function (water maze), and concomitant changes in hippocampal protein expression (GC/MS-MS, western blot). Next, we repeated these experiments in a rat model of weight loss induced by CR. We also measured mitochondrial enzyme activity in rats after weight loss during the fed or fasting state. By using a modified version of the water maze we evaluated cognitive abilities in rats subjected to weight loss by CR or a restricted KD. Results In this study, obesity affected metabolic processes, upregulated hippocampal NF-κB, and induced proteomic differences which were associated with impaired cognition and neurogenesis. Weight loss improved neurogenesis and enhanced cognition. While the expression pattern of some proteins persisted after weight loss, most of the changes appeared de novo revealing metabolic adjustment by overactivation of citrate synthase and downregulation of ATP synthase. As a consequence of fasting, the activity of these enzymes indicated hippocampal adaptation to negative energy balance during the weight loss phase of CR. Moreover, the effects on cognitive abilities measured after weight loss were negatively correlated with the obesity level and were alleviated by KD, which improved cognition when used as a weight loss approach. Conclusions The study shows that cognition and mitochondrial metabolism in the hippocampus are affected by CR- or KD-induced weight loss.
HostingRepository	PRIDE
AnnounceDate	2021-07-02
AnnouncementXML	Submission_2021-07-01_22:59:48.530.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lukasz Marczak
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-11 06:04:25	ID requested
1	2021-07-01 07:15:15	announced
⏵ 2	2021-07-01 22:59:49	announced	2021-07-02: Updated project metadata.

Li, ś, kiewicz AD, Li, ś, kiewicz D, Marczak Ł, Przyby, ł, a M, Grabowska K, Student S, D, ę, biec M, S, ł, ugocka A, Lewin-Kowalik J, Obesity-associated deterioration of the hippocampus is partially restored after weight loss. Brain Behav Immun, 96():212-226(2021) [pubmed]

10.1016/J.BBI.2021.05.030;

submitter keyword: hippocampus, cognition, ketogenic diet, neurogenesis, weight loss,obesity

Lukasz Marczak
contact affiliation	Institute of Bioorganic Chemistry Polish Academy of Sciences
contact email	lukasmar@ibch.poznan.pl
lab head
Lukasz Marczak
contact affiliation	Institute of Bioorganic Chemistry Polish Academy of Sciences
contact email	lukasmar@ibch.poznan.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023070
     1. Label: PRIDE project
     2. Name: Obesity-associated deterioration of the hippocampus is partially restored after weight loss - AWL_ContA