Early and reversible changes to the hippocampal proteome in mice on a high-fat diet

Fiona H. McLean, Fiona M. Campbell, Domenico Sergi, Christine Grant, Amanda C. Morris, Elizabeth A. Hay, Alasdair MacKenzie, Claus-D. Mayer, Rosamund F. Langston, Lynda M. Williams (Corresponding Author)

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Abstract

Background
The rise in global obesity makes it crucial to understand how diet drives obesity-related health conditions, such as premature cognitive decline and Alzheimer’s disease (AD). In AD hippocampal-dependent episodic memory is one of the first types of memory to be impaired. Previous studies have shown that in mice fed a high-fat diet (HFD) episodic memory is rapidly but reversibly impaired.

Methods
In this study we use hippocampal proteomics to investigate the effects of HFD in the hippocampus. Mice were fed either a low-fat diet (LFD) or HFD containing either 10% or 60% (Kcal) from fat for 3 days, 1 week or 2 weeks. One group of mice were fed the HFD for 1 week and then returned to the LFD for a further week. Primary hippocampal cultures were challenged with palmitic acid (PA), the most common long-chain saturated FA in the Western diet, and with the anti-inflammatory, n-3 polyunsaturated FA, docosahexaenoic acid (DHA), or a combination of the two to ascertain effects of these fatty acids on dendritic structure.

Results
HFD-induced changes occur in hippocampal proteins involved in metabolism, inflammation, cell stress, cell signalling, and the cytoskeleton after 3 days, 1 week and 2 weeks of HFD. Replacement of the HFD after 1 week by a low-fat diet (LFD) for a further week resulted in partial recovery of the hippocampal proteome. Microtubule-associated protein 2 (MAP2), one of the earliest proteins changed, was used to investigate the impact of fatty acids (FAs) on hippocampal neuronal morphology. PA challenge resulted in shorter and less arborised dendrites while DHA had no effect when applied alone but counteracted the effects of PA when FAs were used in combination. Dendritic morphology recovered when PA was removed from the cell culture media.

Conclusion
This study provides evidence for the rapid and reversible effects of diet on the hippocampal proteome and the impact of PA and DHA on dendritic structure.
Original languageEnglish
Article number57
Number of pages12
JournalNutrition and Metabolism
Volume16
Issue number1
Early online date23 Aug 2019
DOIs
Publication statusPublished - Dec 2019

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High Fat Diet
Proteome
Palmitic Acid
Fat-Restricted Diet
Docosahexaenoic Acids
Fatty Acids
Episodic Memory
Alzheimer Disease
Obesity
Diet
Microtubule-Associated Proteins
Omega-3 Fatty Acids
Dendrites
Cytoskeleton
Proteomics
Culture Media
Hippocampus
Proteins
Anti-Inflammatory Agents
Cell Culture Techniques

Keywords

  • Hippocampus
  • Proteomics
  • Mice
  • High-fat diet
  • Dendritic morphology
  • ALZHEIMERS-DISEASE BRAIN
  • ACID
  • MECHANISMS
  • IDENTIFICATION
  • FLUID
  • INSULIN-RESISTANCE
  • OXIDATIVELY MODIFIED PROTEINS
  • GROWTH-FACTOR
  • STRESS
  • CREATINE-KINASE

Cite this

Early and reversible changes to the hippocampal proteome in mice on a high-fat diet. / McLean, Fiona H.; Campbell, Fiona M.; Sergi, Domenico; Grant, Christine; Morris, Amanda C.; Hay, Elizabeth A.; MacKenzie, Alasdair; Mayer, Claus-D.; Langston, Rosamund F.; Williams, Lynda M. (Corresponding Author).

In: Nutrition and Metabolism, Vol. 16, No. 1, 57, 12.2019.

Research output: Contribution to journalArticle

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abstract = "BackgroundThe rise in global obesity makes it crucial to understand how diet drives obesity-related health conditions, such as premature cognitive decline and Alzheimer’s disease (AD). In AD hippocampal-dependent episodic memory is one of the first types of memory to be impaired. Previous studies have shown that in mice fed a high-fat diet (HFD) episodic memory is rapidly but reversibly impaired.MethodsIn this study we use hippocampal proteomics to investigate the effects of HFD in the hippocampus. Mice were fed either a low-fat diet (LFD) or HFD containing either 10{\%} or 60{\%} (Kcal) from fat for 3 days, 1 week or 2 weeks. One group of mice were fed the HFD for 1 week and then returned to the LFD for a further week. Primary hippocampal cultures were challenged with palmitic acid (PA), the most common long-chain saturated FA in the Western diet, and with the anti-inflammatory, n-3 polyunsaturated FA, docosahexaenoic acid (DHA), or a combination of the two to ascertain effects of these fatty acids on dendritic structure.ResultsHFD-induced changes occur in hippocampal proteins involved in metabolism, inflammation, cell stress, cell signalling, and the cytoskeleton after 3 days, 1 week and 2 weeks of HFD. Replacement of the HFD after 1 week by a low-fat diet (LFD) for a further week resulted in partial recovery of the hippocampal proteome. Microtubule-associated protein 2 (MAP2), one of the earliest proteins changed, was used to investigate the impact of fatty acids (FAs) on hippocampal neuronal morphology. PA challenge resulted in shorter and less arborised dendrites while DHA had no effect when applied alone but counteracted the effects of PA when FAs were used in combination. Dendritic morphology recovered when PA was removed from the cell culture media.ConclusionThis study provides evidence for the rapid and reversible effects of diet on the hippocampal proteome and the impact of PA and DHA on dendritic structure.",
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author = "McLean, {Fiona H.} and Campbell, {Fiona M.} and Domenico Sergi and Christine Grant and Morris, {Amanda C.} and Hay, {Elizabeth A.} and Alasdair MacKenzie and Claus-D. Mayer and Langston, {Rosamund F.} and Williams, {Lynda M.}",
note = "Funding LMW, FMC, CG, ACM and C-DM were funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). FHM was supported by an EASTBIO DTP BBSRC studentship. DS was supported by a SULSA studentship.",
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T1 - Early and reversible changes to the hippocampal proteome in mice on a high-fat diet

AU - McLean, Fiona H.

AU - Campbell, Fiona M.

AU - Sergi, Domenico

AU - Grant, Christine

AU - Morris, Amanda C.

AU - Hay, Elizabeth A.

AU - MacKenzie, Alasdair

AU - Mayer, Claus-D.

AU - Langston, Rosamund F.

AU - Williams, Lynda M.

N1 - Funding LMW, FMC, CG, ACM and C-DM were funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). FHM was supported by an EASTBIO DTP BBSRC studentship. DS was supported by a SULSA studentship.

PY - 2019/12

Y1 - 2019/12

N2 - BackgroundThe rise in global obesity makes it crucial to understand how diet drives obesity-related health conditions, such as premature cognitive decline and Alzheimer’s disease (AD). In AD hippocampal-dependent episodic memory is one of the first types of memory to be impaired. Previous studies have shown that in mice fed a high-fat diet (HFD) episodic memory is rapidly but reversibly impaired.MethodsIn this study we use hippocampal proteomics to investigate the effects of HFD in the hippocampus. Mice were fed either a low-fat diet (LFD) or HFD containing either 10% or 60% (Kcal) from fat for 3 days, 1 week or 2 weeks. One group of mice were fed the HFD for 1 week and then returned to the LFD for a further week. Primary hippocampal cultures were challenged with palmitic acid (PA), the most common long-chain saturated FA in the Western diet, and with the anti-inflammatory, n-3 polyunsaturated FA, docosahexaenoic acid (DHA), or a combination of the two to ascertain effects of these fatty acids on dendritic structure.ResultsHFD-induced changes occur in hippocampal proteins involved in metabolism, inflammation, cell stress, cell signalling, and the cytoskeleton after 3 days, 1 week and 2 weeks of HFD. Replacement of the HFD after 1 week by a low-fat diet (LFD) for a further week resulted in partial recovery of the hippocampal proteome. Microtubule-associated protein 2 (MAP2), one of the earliest proteins changed, was used to investigate the impact of fatty acids (FAs) on hippocampal neuronal morphology. PA challenge resulted in shorter and less arborised dendrites while DHA had no effect when applied alone but counteracted the effects of PA when FAs were used in combination. Dendritic morphology recovered when PA was removed from the cell culture media.ConclusionThis study provides evidence for the rapid and reversible effects of diet on the hippocampal proteome and the impact of PA and DHA on dendritic structure.

AB - BackgroundThe rise in global obesity makes it crucial to understand how diet drives obesity-related health conditions, such as premature cognitive decline and Alzheimer’s disease (AD). In AD hippocampal-dependent episodic memory is one of the first types of memory to be impaired. Previous studies have shown that in mice fed a high-fat diet (HFD) episodic memory is rapidly but reversibly impaired.MethodsIn this study we use hippocampal proteomics to investigate the effects of HFD in the hippocampus. Mice were fed either a low-fat diet (LFD) or HFD containing either 10% or 60% (Kcal) from fat for 3 days, 1 week or 2 weeks. One group of mice were fed the HFD for 1 week and then returned to the LFD for a further week. Primary hippocampal cultures were challenged with palmitic acid (PA), the most common long-chain saturated FA in the Western diet, and with the anti-inflammatory, n-3 polyunsaturated FA, docosahexaenoic acid (DHA), or a combination of the two to ascertain effects of these fatty acids on dendritic structure.ResultsHFD-induced changes occur in hippocampal proteins involved in metabolism, inflammation, cell stress, cell signalling, and the cytoskeleton after 3 days, 1 week and 2 weeks of HFD. Replacement of the HFD after 1 week by a low-fat diet (LFD) for a further week resulted in partial recovery of the hippocampal proteome. Microtubule-associated protein 2 (MAP2), one of the earliest proteins changed, was used to investigate the impact of fatty acids (FAs) on hippocampal neuronal morphology. PA challenge resulted in shorter and less arborised dendrites while DHA had no effect when applied alone but counteracted the effects of PA when FAs were used in combination. Dendritic morphology recovered when PA was removed from the cell culture media.ConclusionThis study provides evidence for the rapid and reversible effects of diet on the hippocampal proteome and the impact of PA and DHA on dendritic structure.

KW - Hippocampus

KW - Proteomics

KW - Mice

KW - High-fat diet

KW - Dendritic morphology

KW - ALZHEIMERS-DISEASE BRAIN

KW - ACID

KW - MECHANISMS

KW - IDENTIFICATION

KW - FLUID

KW - INSULIN-RESISTANCE

KW - OXIDATIVELY MODIFIED PROTEINS

KW - GROWTH-FACTOR

KW - STRESS

KW - CREATINE-KINASE

UR - http://www.ncbi.nlm.nih.gov/pubmed/31462902 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6708244

UR - http://www.mendeley.com/research/early-reversible-changes-hippocampal-proteome-mice-highfat-diet

U2 - 10.1186/s12986-019-0387-y

DO - 10.1186/s12986-019-0387-y

M3 - Article

C2 - 31462902

VL - 16

JO - Nutrition and Metabolism

JF - Nutrition and Metabolism

SN - 1743-7075

IS - 1

M1 - 57

ER -