Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor

Deng Bao Yang; Lin Gao; Xin Yu Liu; Yan Chao Xu; C Hambly; De Hua Wang; John R Speakman

doi:10.1016/j.molmet.2023.101724

Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor

Deng Bao Yang, Lin Gao, Xin Yu Liu, Yan Chao Xu, C Hambly, De Hua Wang^* (Corresponding Author), John R Speakman^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection.

RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance.

CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the 'lipotoxicity hypothesis'. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.

Original language	English
Article number	101724
Number of pages	12
Journal	Molecular Metabolism
Volume	73
Early online date	13 Apr 2023
DOIs	https://doi.org/10.1016/j.molmet.2023.101724
Publication status	Published - Jul 2023

Bibliographical note

FUNDING
This work was funded by the National Science Foundation of China (92057206) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030000) both to JRS, a small grant to JRS and DHW, and a ‘Great Wall’ professorship to JRS, both from the CAS-NovoNordisk Foundation. JRS was also supported by a 1000 talents professorship and a Wolfson merit award from the Royal Society.
Acknowledgements
We are grateful to all the members of the Molecular Energetics Group (IDGB) and the Animal Physiological Ecology Group (IOZ) for their help with the experiment and discussion of the results. DBY and XYL performed the experiment, analysed the data and drafted the manuscript. GL analysed the data and wrote parts of the manuscript. YCX contributed to data collection. DHW and JRS designed the experiment, analysed the data and rewrote and edited the manuscript. Two anonymous reviewers provided many helpful suggestions that improved the manuscript.

Data Availability Statement

Data will be made available on request.

Keywords

brandt's vole
photoperiod-induced obesity
high-fat diet
ectopic fat deposition
glucose tolerance

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Yang_etal_MM_Disentangling_the_Effects_VOR
2023 Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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Cite this

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title = "Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor",

abstract = "OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection.RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance.CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the 'lipotoxicity hypothesis'. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.",

keywords = "brandt's vole, photoperiod-induced obesity, high-fat diet, ectopic fat deposition, glucose tolerance",

author = "Yang, {Deng Bao} and Lin Gao and Liu, {Xin Yu} and Xu, {Yan Chao} and C Hambly and Wang, {De Hua} and Speakman, {John R}",

note = "FUNDING This work was funded by the National Science Foundation of China (92057206) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030000) both to JRS, a small grant to JRS and DHW, and a {\textquoteleft}Great Wall{\textquoteright} professorship to JRS, both from the CAS-NovoNordisk Foundation. JRS was also supported by a 1000 talents professorship and a Wolfson merit award from the Royal Society. Acknowledgements We are grateful to all the members of the Molecular Energetics Group (IDGB) and the Animal Physiological Ecology Group (IOZ) for their help with the experiment and discussion of the results. DBY and XYL performed the experiment, analysed the data and drafted the manuscript. GL analysed the data and wrote parts of the manuscript. YCX contributed to data collection. DHW and JRS designed the experiment, analysed the data and rewrote and edited the manuscript. Two anonymous reviewers provided many helpful suggestions that improved the manuscript.",

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journal = "Molecular Metabolism",

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TY - JOUR

T1 - Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor

AU - Yang, Deng Bao

AU - Gao, Lin

AU - Liu, Xin Yu

AU - Xu, Yan Chao

AU - Hambly, C

AU - Wang, De Hua

AU - Speakman, John R

N1 - FUNDING This work was funded by the National Science Foundation of China (92057206) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030000) both to JRS, a small grant to JRS and DHW, and a ‘Great Wall’ professorship to JRS, both from the CAS-NovoNordisk Foundation. JRS was also supported by a 1000 talents professorship and a Wolfson merit award from the Royal Society. Acknowledgements We are grateful to all the members of the Molecular Energetics Group (IDGB) and the Animal Physiological Ecology Group (IOZ) for their help with the experiment and discussion of the results. DBY and XYL performed the experiment, analysed the data and drafted the manuscript. GL analysed the data and wrote parts of the manuscript. YCX contributed to data collection. DHW and JRS designed the experiment, analysed the data and rewrote and edited the manuscript. Two anonymous reviewers provided many helpful suggestions that improved the manuscript.

PY - 2023/7

Y1 - 2023/7

N2 - OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection.RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance.CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the 'lipotoxicity hypothesis'. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.

AB - OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection.RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance.CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the 'lipotoxicity hypothesis'. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.

KW - brandt's vole

KW - photoperiod-induced obesity

KW - high-fat diet

KW - ectopic fat deposition

KW - glucose tolerance

U2 - 10.1016/j.molmet.2023.101724

DO - 10.1016/j.molmet.2023.101724

M3 - Article

C2 - 37061130

SN - 2212-8778

VL - 73

JO - Molecular Metabolism

JF - Molecular Metabolism

M1 - 101724

ER -

Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

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