Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice

Sumei Hu, Lu Wang, Dengbao Yang, Li Li, Jacques Togo, Yingga Wu, Quansheng Liu, Baoguo Li, Min Li, Guanlin Wang, Xueying Zhang, Chaoqun Niu, Jianbo Li, Yanchao Xu, Elspeth Couper, Andrew Whittington-Davies, Mohsen Mazidi, Lijuan Luo, Shengnan Wang, Alex Douglas & 1 others John R Speakman

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Abstract

The impacts of different macronutrients on body weight regulation remain unresolved, with different studies suggesting increased dietary fat, increased carbohydrates (particularly sugars), or reduced protein may all stimulate overconsumption and drive obesity. We exposed C57BL/6 mice to 29 different diets varying from 8.3% to 80% fat, 10% to 80% carbohydrate, 5% to 30% protein, and 5% to 30% sucrose. Only increased dietary fat content was associated with elevated energy intake and adiposity. This response was associated with increased gene expression in the 5-HT receptors, and the dopamine and opioid signaling pathways in the hypothalamus. We replicated the core findings in four other mouse strains (DBA/2, BALB/c, FVB, and C3H). Mice regulate their food consumption primarily to meet an energy rather than a protein target, but this system can be over-ridden by hedonic factors linked to fat, but not sucrose, consumption.

Original languageEnglish
Pages (from-to)415-431
Number of pages15
JournalCell Metabolism
Volume28
Issue number3
Early online date12 Jul 2018
DOIs
Publication statusPublished - Sep 2018

Fingerprint

Dietary Fats
Adiposity
Energy Intake
Carbohydrates
Sucrose
Fats
Inbred DBA Mouse
Proteins
Pleasure
Serotonin Receptors
Inbred C57BL Mouse
Opioid Analgesics
Hypothalamus
Dopamine
Obesity
Body Weight
Diet
Gene Expression
Food

Keywords

  • Journal Article
  • fat intake
  • sucrose intake
  • protein leverage hypothesis
  • energy regulation
  • hedonic overdrive
  • mice
  • hypothalamic hunger pathway
  • obesity
  • FGF signalling
  • mTOR signalling

Cite this

Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice. / Hu, Sumei; Wang, Lu; Yang, Dengbao; Li, Li; Togo, Jacques; Wu, Yingga; Liu, Quansheng; Li, Baoguo; Li, Min; Wang, Guanlin; Zhang, Xueying; Niu, Chaoqun; Li, Jianbo; Xu, Yanchao; Couper, Elspeth; Whittington-Davies, Andrew; Mazidi, Mohsen; Luo, Lijuan; Wang, Shengnan; Douglas, Alex; Speakman, John R.

In: Cell Metabolism, Vol. 28, No. 3, 09.2018, p. 415-431.

Research output: Contribution to journalArticle

Hu, S, Wang, L, Yang, D, Li, L, Togo, J, Wu, Y, Liu, Q, Li, B, Li, M, Wang, G, Zhang, X, Niu, C, Li, J, Xu, Y, Couper, E, Whittington-Davies, A, Mazidi, M, Luo, L, Wang, S, Douglas, A & Speakman, JR 2018, 'Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice', Cell Metabolism, vol. 28, no. 3, pp. 415-431. https://doi.org/10.1016/j.cmet.2018.06.010
Hu, Sumei ; Wang, Lu ; Yang, Dengbao ; Li, Li ; Togo, Jacques ; Wu, Yingga ; Liu, Quansheng ; Li, Baoguo ; Li, Min ; Wang, Guanlin ; Zhang, Xueying ; Niu, Chaoqun ; Li, Jianbo ; Xu, Yanchao ; Couper, Elspeth ; Whittington-Davies, Andrew ; Mazidi, Mohsen ; Luo, Lijuan ; Wang, Shengnan ; Douglas, Alex ; Speakman, John R. / Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice. In: Cell Metabolism. 2018 ; Vol. 28, No. 3. pp. 415-431.
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abstract = "The impacts of different macronutrients on body weight regulation remain unresolved, with different studies suggesting increased dietary fat, increased carbohydrates (particularly sugars), or reduced protein may all stimulate overconsumption and drive obesity. We exposed C57BL/6 mice to 29 different diets varying from 8.3{\%} to 80{\%} fat, 10{\%} to 80{\%} carbohydrate, 5{\%} to 30{\%} protein, and 5{\%} to 30{\%} sucrose. Only increased dietary fat content was associated with elevated energy intake and adiposity. This response was associated with increased gene expression in the 5-HT receptors, and the dopamine and opioid signaling pathways in the hypothalamus. We replicated the core findings in four other mouse strains (DBA/2, BALB/c, FVB, and C3H). Mice regulate their food consumption primarily to meet an energy rather than a protein target, but this system can be over-ridden by hedonic factors linked to fat, but not sucrose, consumption.",
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AU - Togo, Jacques

AU - Wu, Yingga

AU - Liu, Quansheng

AU - Li, Baoguo

AU - Li, Min

AU - Wang, Guanlin

AU - Zhang, Xueying

AU - Niu, Chaoqun

AU - Li, Jianbo

AU - Xu, Yanchao

AU - Couper, Elspeth

AU - Whittington-Davies, Andrew

AU - Mazidi, Mohsen

AU - Luo, Lijuan

AU - Wang, Shengnan

AU - Douglas, Alex

AU - Speakman, John R

N1 - Full details of methods and materials are provided in the supplementary materials and the project has been registered at the Open Science Framework (https://doi.org/10.17605/OSF.IO/YH9GZ). The study was funded by the Chinese Academy of Sciences Strategic Program (XDB13030100), the 1000 Talents program, and a Wolfson merit award to J.R.S., and by the National Natural Science Foundation of China (31570409) and funds from Guangdong Academy of Sciences (2017GDASCX-0107) to Q.L.

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N2 - The impacts of different macronutrients on body weight regulation remain unresolved, with different studies suggesting increased dietary fat, increased carbohydrates (particularly sugars), or reduced protein may all stimulate overconsumption and drive obesity. We exposed C57BL/6 mice to 29 different diets varying from 8.3% to 80% fat, 10% to 80% carbohydrate, 5% to 30% protein, and 5% to 30% sucrose. Only increased dietary fat content was associated with elevated energy intake and adiposity. This response was associated with increased gene expression in the 5-HT receptors, and the dopamine and opioid signaling pathways in the hypothalamus. We replicated the core findings in four other mouse strains (DBA/2, BALB/c, FVB, and C3H). Mice regulate their food consumption primarily to meet an energy rather than a protein target, but this system can be over-ridden by hedonic factors linked to fat, but not sucrose, consumption.

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KW - obesity

KW - FGF signalling

KW - mTOR signalling

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