Periodized low protein-high carbohydrate diet confers potent, but transient, metabolic improvements

Zhencheng Li; Mette Line Rasmussen; Jingwen Li; Carlos Henriquez-Olguin; Jonas Roland Knudsen; Agnete Bjerregaard Madsen; Eva Sanchez-Quant; Maximilian Kleinert; Thomas Elbenhardt Jensen

doi:10.1016/j.molmet.2018.08.008

Periodized low protein-high carbohydrate diet confers potent, but transient, metabolic improvements

Zhencheng Li, Mette Line Rasmussen, Jingwen Li, Carlos Henriquez-Olguin, Jonas Roland Knudsen, Agnete Bjerregaard Madsen, Eva Sanchez-Quant, Maximilian Kleinert, Thomas Elbenhardt Jensen^*

^*Corresponding author af dette arbejde

August Krogh Sektionen for Molekylær Fysiologi

4 Citationer (Scopus)

70 Downloads (Pure)

Abstract

Objective: Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated. Presently, we aimed to provide proof-of-concept data in mice of the efficacy of pLPHC and to explore the potential interactions with concurrent exercise training.

Methods: A detailed phenotypic and molecular characterization of mice undergoing different durations of 14 d LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without concurrent access to activity wheels allowing voluntary exercise training.

Results: pLPHC conferred metabolic benefits similar to chronic LPHC, including increased FGF21 and adaptive thermogenesis, obesity-protection despite increased total energy intake and improved insulin sensitivity. The improved insulin sensitivity showed large fluctuations between diet periods and was lost within 14 days of switching back to control diet. Parallel exercise training improved weight maintenance but impaired the FGF21 response to pLPHC whereas repeated pLPHC cycles progressively augmented this response. Both the FGF21 suppression by exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA in liver, suggesting dependence on liver integrated stress response.

Conclusion: These results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration.

Originalsprog	Engelsk
Tidsskrift	Molecular Metabolism
Vol/bind	17
Sider (fra-til)	112-121
Antal sider	10
ISSN	2212-8778
DOI	https://doi.org/10.1016/j.molmet.2018.08.008
Status	Udgivet - nov. 2018

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10.1016/j.molmet.2018.08.008Licens: CC BY-NC-ND

Li et al_Molecular Metabolism_2018_Vol 17_112-121Forlagets udgivne version, 2,01 MBLicens: CC BY-NC-ND

Citationsformater

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title = "Periodized low protein-high carbohydrate diet confers potent, but transient, metabolic improvements",

abstract = "Objective: Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated. Presently, we aimed to provide proof-of-concept data in mice of the efficacy of pLPHC and to explore the potential interactions with concurrent exercise training. Methods: A detailed phenotypic and molecular characterization of mice undergoing different durations of 14 d LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without concurrent access to activity wheels allowing voluntary exercise training. Results: pLPHC conferred metabolic benefits similar to chronic LPHC, including increased FGF21 and adaptive thermogenesis, obesity-protection despite increased total energy intake and improved insulin sensitivity. The improved insulin sensitivity showed large fluctuations between diet periods and was lost within 14 days of switching back to control diet. Parallel exercise training improved weight maintenance but impaired the FGF21 response to pLPHC whereas repeated pLPHC cycles progressively augmented this response. Both the FGF21 suppression by exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA in liver, suggesting dependence on liver integrated stress response. Conclusion: These results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration.",

keywords = "Dietary restriction, Exercise, FGF21, Glucose metabolism, Integrated stress response, Obesity, Periodized diet",

author = "Zhencheng Li and Rasmussen, {Mette Line} and Jingwen Li and Carlos Henriquez-Olguin and Knudsen, {Jonas Roland} and Madsen, {Agnete Bjerregaard} and Eva Sanchez-Quant and Maximilian Kleinert and Jensen, {Thomas Elbenhardt}",

note = "CURIS 2018 NEXS 316",

year = "2018",

month = nov,

doi = "10.1016/j.molmet.2018.08.008",

language = "English",

volume = "17",

pages = "112--121",

journal = "Molecular Metabolism",

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TY - JOUR

T1 - Periodized low protein-high carbohydrate diet confers potent, but transient, metabolic improvements

AU - Li, Zhencheng

AU - Rasmussen, Mette Line

AU - Li, Jingwen

AU - Henriquez-Olguin, Carlos

AU - Knudsen, Jonas Roland

AU - Madsen, Agnete Bjerregaard

AU - Sanchez-Quant, Eva

AU - Kleinert, Maximilian

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2018 NEXS 316

PY - 2018/11

Y1 - 2018/11

N2 - Objective: Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated. Presently, we aimed to provide proof-of-concept data in mice of the efficacy of pLPHC and to explore the potential interactions with concurrent exercise training. Methods: A detailed phenotypic and molecular characterization of mice undergoing different durations of 14 d LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without concurrent access to activity wheels allowing voluntary exercise training. Results: pLPHC conferred metabolic benefits similar to chronic LPHC, including increased FGF21 and adaptive thermogenesis, obesity-protection despite increased total energy intake and improved insulin sensitivity. The improved insulin sensitivity showed large fluctuations between diet periods and was lost within 14 days of switching back to control diet. Parallel exercise training improved weight maintenance but impaired the FGF21 response to pLPHC whereas repeated pLPHC cycles progressively augmented this response. Both the FGF21 suppression by exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA in liver, suggesting dependence on liver integrated stress response. Conclusion: These results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration.

AB - Objective: Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated. Presently, we aimed to provide proof-of-concept data in mice of the efficacy of pLPHC and to explore the potential interactions with concurrent exercise training. Methods: A detailed phenotypic and molecular characterization of mice undergoing different durations of 14 d LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without concurrent access to activity wheels allowing voluntary exercise training. Results: pLPHC conferred metabolic benefits similar to chronic LPHC, including increased FGF21 and adaptive thermogenesis, obesity-protection despite increased total energy intake and improved insulin sensitivity. The improved insulin sensitivity showed large fluctuations between diet periods and was lost within 14 days of switching back to control diet. Parallel exercise training improved weight maintenance but impaired the FGF21 response to pLPHC whereas repeated pLPHC cycles progressively augmented this response. Both the FGF21 suppression by exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA in liver, suggesting dependence on liver integrated stress response. Conclusion: These results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration.

KW - Dietary restriction

KW - Exercise

KW - FGF21

KW - Glucose metabolism

KW - Integrated stress response

KW - Obesity

KW - Periodized diet

U2 - 10.1016/j.molmet.2018.08.008

DO - 10.1016/j.molmet.2018.08.008

M3 - Journal article

C2 - 30193785

AN - SCOPUS:85052823923

SN - 2212-8778

VL - 17

SP - 112

EP - 121

JO - Molecular Metabolism

JF - Molecular Metabolism

ER -

Periodized low protein-high carbohydrate diet confers potent, but transient, metabolic improvements

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