A high-fat diet induces rapid changes in the mouse hypothalamic proteome

Fiona H. McLean, Fiona M. Campbell, Rosamund F. Langston, Domenico Sergi, Cibell Resch, Christine Grant, Amanda C. Morris, Claus D. Mayer, Lynda M. Williams (Lead / Corresponding author)

Research output: Contribution to journalArticle

32 Downloads (Pure)

Abstract

Background: Prolonged over-consumption of a high-fat diet (HFD) commonly leads to obesity and insulin resistance. However, even 3 days of HFD consumption has been linked to inflammation within the key homeostatic brain region, the hypothalamus.

Methods: Mice were fed either a low-fat diet (LFD) or HFD containing 10% or 60% (Kcal) respectively from fat for 3 days. Mice were weighed, food intake measured and glucose tolerance calculated using intraperitoneal glucose tolerance tests (IPGTT). Proteomic analysis was carried out to determine if hypothalamic proteins were changed by a HFD. The direct effects of dietary fatty acids on mitochondrial morphology and on one of the proteins most changed by a HFD, dihydropyrimidinase-related protein 2 (DRP-2) a microtubule-associated protein which regulates microtubule dynamics, were also tested in mHypoE-N42 (N42) neuronal cells challenged with palmitic acid (PA) and oleic acid (OA).

Results: Mice on the HFD, as expected, showed increased adiposity and glucose intolerance. Hypothalamic proteomic analysis revealed changes in 104 spots after 3 days on HFD, which, when identified by LC/MS/MS, were found to represent 78 proteins mainly associated with cytoskeleton and synaptic plasticity, stress response, glucose metabolism and mitochondrial function. Over half of the changed proteins have also been reported to be changed in neurodegenerative conditions such as Alzheimer's disease. Also,in N42 neurons mitochondrial morphology and DRP-2 levels were altered by PA but not by OA.

Conclusion: These results demonstrate that within 3 days, there is a relatively large effect of HFD on the hypothalamic proteome indicative of cellular stress, altered synaptic plasticity and mitochondrial function, but not inflammation. Changes in N42 cells show an effect of PA but not OA on DRP-2 and on mitochondrial morphology indicating that long-chain saturated fatty acids damage neuronal function.

Original languageEnglish
Article number26
Pages (from-to)1-16
Number of pages16
JournalNutrition and Metabolism
Volume16
DOIs
Publication statusPublished - 29 Apr 2019

Fingerprint

High Fat Diet
Proteome
Palmitic Acid
Oleic Acid
Neuronal Plasticity
Proteomics
Proteins
Fatty Acids
Inflammation
Glucose
Fat-Restricted Diet
Microtubule-Associated Proteins
Glucose Intolerance
Adiposity
Glucose Tolerance Test
Cytoskeleton
Microtubules
Hypothalamus
Insulin Resistance
Alzheimer Disease

Keywords

  • High-fat diet
  • Hypothalamus
  • Mice
  • Neuronal plasticity
  • Proteomics

Cite this

McLean, Fiona H. ; Campbell, Fiona M. ; Langston, Rosamund F. ; Sergi, Domenico ; Resch, Cibell ; Grant, Christine ; Morris, Amanda C. ; Mayer, Claus D. ; Williams, Lynda M. / A high-fat diet induces rapid changes in the mouse hypothalamic proteome. In: Nutrition and Metabolism. 2019 ; Vol. 16. pp. 1-16.
@article{8ad2235c6bbc43e6b7fcde2955113e0e,
title = "A high-fat diet induces rapid changes in the mouse hypothalamic proteome",
abstract = "Background: Prolonged over-consumption of a high-fat diet (HFD) commonly leads to obesity and insulin resistance. However, even 3 days of HFD consumption has been linked to inflammation within the key homeostatic brain region, the hypothalamus.Methods: Mice were fed either a low-fat diet (LFD) or HFD containing 10{\%} or 60{\%} (Kcal) respectively from fat for 3 days. Mice were weighed, food intake measured and glucose tolerance calculated using intraperitoneal glucose tolerance tests (IPGTT). Proteomic analysis was carried out to determine if hypothalamic proteins were changed by a HFD. The direct effects of dietary fatty acids on mitochondrial morphology and on one of the proteins most changed by a HFD, dihydropyrimidinase-related protein 2 (DRP-2) a microtubule-associated protein which regulates microtubule dynamics, were also tested in mHypoE-N42 (N42) neuronal cells challenged with palmitic acid (PA) and oleic acid (OA).Results: Mice on the HFD, as expected, showed increased adiposity and glucose intolerance. Hypothalamic proteomic analysis revealed changes in 104 spots after 3 days on HFD, which, when identified by LC/MS/MS, were found to represent 78 proteins mainly associated with cytoskeleton and synaptic plasticity, stress response, glucose metabolism and mitochondrial function. Over half of the changed proteins have also been reported to be changed in neurodegenerative conditions such as Alzheimer's disease. Also,in N42 neurons mitochondrial morphology and DRP-2 levels were altered by PA but not by OA.Conclusion: These results demonstrate that within 3 days, there is a relatively large effect of HFD on the hypothalamic proteome indicative of cellular stress, altered synaptic plasticity and mitochondrial function, but not inflammation. Changes in N42 cells show an effect of PA but not OA on DRP-2 and on mitochondrial morphology indicating that long-chain saturated fatty acids damage neuronal function.",
keywords = "High-fat diet, Hypothalamus, Mice, Neuronal plasticity, Proteomics",
author = "McLean, {Fiona H.} and Campbell, {Fiona M.} and Langston, {Rosamund F.} and Domenico Sergi and Cibell Resch and Christine Grant and Morris, {Amanda C.} and Mayer, {Claus D.} and Williams, {Lynda M.}",
year = "2019",
month = "4",
day = "29",
doi = "10.1186/s12986-019-0352-9",
language = "English",
volume = "16",
pages = "1--16",
journal = "Annals of Nutrition and Metabolism",
issn = "0250-6807",
publisher = "Karger",

}

McLean, FH, Campbell, FM, Langston, RF, Sergi, D, Resch, C, Grant, C, Morris, AC, Mayer, CD & Williams, LM 2019, 'A high-fat diet induces rapid changes in the mouse hypothalamic proteome', Nutrition and Metabolism, vol. 16, 26, pp. 1-16. https://doi.org/10.1186/s12986-019-0352-9

A high-fat diet induces rapid changes in the mouse hypothalamic proteome. / McLean, Fiona H.; Campbell, Fiona M.; Langston, Rosamund F.; Sergi, Domenico; Resch, Cibell; Grant, Christine; Morris, Amanda C.; Mayer, Claus D.; Williams, Lynda M. (Lead / Corresponding author).

In: Nutrition and Metabolism, Vol. 16, 26, 29.04.2019, p. 1-16.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A high-fat diet induces rapid changes in the mouse hypothalamic proteome

AU - McLean, Fiona H.

AU - Campbell, Fiona M.

AU - Langston, Rosamund F.

AU - Sergi, Domenico

AU - Resch, Cibell

AU - Grant, Christine

AU - Morris, Amanda C.

AU - Mayer, Claus D.

AU - Williams, Lynda M.

PY - 2019/4/29

Y1 - 2019/4/29

N2 - Background: Prolonged over-consumption of a high-fat diet (HFD) commonly leads to obesity and insulin resistance. However, even 3 days of HFD consumption has been linked to inflammation within the key homeostatic brain region, the hypothalamus.Methods: Mice were fed either a low-fat diet (LFD) or HFD containing 10% or 60% (Kcal) respectively from fat for 3 days. Mice were weighed, food intake measured and glucose tolerance calculated using intraperitoneal glucose tolerance tests (IPGTT). Proteomic analysis was carried out to determine if hypothalamic proteins were changed by a HFD. The direct effects of dietary fatty acids on mitochondrial morphology and on one of the proteins most changed by a HFD, dihydropyrimidinase-related protein 2 (DRP-2) a microtubule-associated protein which regulates microtubule dynamics, were also tested in mHypoE-N42 (N42) neuronal cells challenged with palmitic acid (PA) and oleic acid (OA).Results: Mice on the HFD, as expected, showed increased adiposity and glucose intolerance. Hypothalamic proteomic analysis revealed changes in 104 spots after 3 days on HFD, which, when identified by LC/MS/MS, were found to represent 78 proteins mainly associated with cytoskeleton and synaptic plasticity, stress response, glucose metabolism and mitochondrial function. Over half of the changed proteins have also been reported to be changed in neurodegenerative conditions such as Alzheimer's disease. Also,in N42 neurons mitochondrial morphology and DRP-2 levels were altered by PA but not by OA.Conclusion: These results demonstrate that within 3 days, there is a relatively large effect of HFD on the hypothalamic proteome indicative of cellular stress, altered synaptic plasticity and mitochondrial function, but not inflammation. Changes in N42 cells show an effect of PA but not OA on DRP-2 and on mitochondrial morphology indicating that long-chain saturated fatty acids damage neuronal function.

AB - Background: Prolonged over-consumption of a high-fat diet (HFD) commonly leads to obesity and insulin resistance. However, even 3 days of HFD consumption has been linked to inflammation within the key homeostatic brain region, the hypothalamus.Methods: Mice were fed either a low-fat diet (LFD) or HFD containing 10% or 60% (Kcal) respectively from fat for 3 days. Mice were weighed, food intake measured and glucose tolerance calculated using intraperitoneal glucose tolerance tests (IPGTT). Proteomic analysis was carried out to determine if hypothalamic proteins were changed by a HFD. The direct effects of dietary fatty acids on mitochondrial morphology and on one of the proteins most changed by a HFD, dihydropyrimidinase-related protein 2 (DRP-2) a microtubule-associated protein which regulates microtubule dynamics, were also tested in mHypoE-N42 (N42) neuronal cells challenged with palmitic acid (PA) and oleic acid (OA).Results: Mice on the HFD, as expected, showed increased adiposity and glucose intolerance. Hypothalamic proteomic analysis revealed changes in 104 spots after 3 days on HFD, which, when identified by LC/MS/MS, were found to represent 78 proteins mainly associated with cytoskeleton and synaptic plasticity, stress response, glucose metabolism and mitochondrial function. Over half of the changed proteins have also been reported to be changed in neurodegenerative conditions such as Alzheimer's disease. Also,in N42 neurons mitochondrial morphology and DRP-2 levels were altered by PA but not by OA.Conclusion: These results demonstrate that within 3 days, there is a relatively large effect of HFD on the hypothalamic proteome indicative of cellular stress, altered synaptic plasticity and mitochondrial function, but not inflammation. Changes in N42 cells show an effect of PA but not OA on DRP-2 and on mitochondrial morphology indicating that long-chain saturated fatty acids damage neuronal function.

KW - High-fat diet

KW - Hypothalamus

KW - Mice

KW - Neuronal plasticity

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=85065234021&partnerID=8YFLogxK

U2 - 10.1186/s12986-019-0352-9

DO - 10.1186/s12986-019-0352-9

M3 - Article

VL - 16

SP - 1

EP - 16

JO - Annals of Nutrition and Metabolism

JF - Annals of Nutrition and Metabolism

SN - 0250-6807

M1 - 26

ER -