Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat

Mads Thue Fejerskov Damgaard; Simone I. Pærregaard; Ida Søgaard; Marianne Agerholm  Andersen; Joseph N. Paulson; Jonas Thue Treebak; Christian Sina; Jacob Bak Holm; Karsten Kristiansen; Benjamin Anderschou Holbech Jensen

doi:10.1016/j.jnutbio.2017.09.026

Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat

Mads Thue Fejerskov Damgaard, Simone I. Pærregaard, Ida Søgaard, Marianne Agerholm Andersen, Joseph N. Paulson, Jonas Thue Treebak, Christian Sina, Jacob Bak Holm, Karsten Kristiansen, Benjamin Anderschou Holbech Jensen

6 Citations (Scopus)

Abstract

Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined. We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters. Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly developed impaired glucose clearance followed by a gradual improvement from week 8 to week 39. All groups had similar responses to insulin 40 weeks post diet initiation despite severe nonalcoholic steatohepatitis in SOD-fed mice. We conclude that age-related alterations in glucose regulation may occur in both lean and obese mice and are modulated by dietary fat as indicated by the sustained metabolic homeostasis observed in mice fed ω3-polyunsaturated fatty acids.

Original language	English
Journal	Journal of Nutritional Biochemistry
Volume	54
Pages (from-to)	66-76
Number of pages	11
ISSN	0955-2863
DOIs	https://doi.org/10.1016/j.jnutbio.2017.09.026
Publication status	Published - Apr 2018

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10.1016/j.jnutbio.2017.09.026

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Damgaard, M. T. F., Pærregaard, S. I., Søgaard, I., Andersen, M. A., Paulson, J. N., Treebak, J. T., Sina, C., Holm, J. B., Kristiansen, K., & Jensen, B. A. H. (2018). Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat. Journal of Nutritional Biochemistry, 54, 66-76. https://doi.org/10.1016/j.jnutbio.2017.09.026

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title = "Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat",

abstract = "Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined. We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters. Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly developed impaired glucose clearance followed by a gradual improvement from week 8 to week 39. All groups had similar responses to insulin 40 weeks post diet initiation despite severe nonalcoholic steatohepatitis in SOD-fed mice. We conclude that age-related alterations in glucose regulation may occur in both lean and obese mice and are modulated by dietary fat as indicated by the sustained metabolic homeostasis observed in mice fed ω3-polyunsaturated fatty acids.",

author = "Damgaard, {Mads Thue Fejerskov} and P{\ae}rregaard, {Simone I.} and Ida S{\o}gaard and Andersen, {Marianne Agerholm} and Paulson, {Joseph N.} and Treebak, {Jonas Thue} and Christian Sina and Holm, {Jacob Bak} and Karsten Kristiansen and Jensen, {Benjamin Anderschou Holbech}",

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doi = "10.1016/j.jnutbio.2017.09.026",

language = "English",

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AU - Damgaard, Mads Thue Fejerskov

AU - Pærregaard, Simone I.

AU - Søgaard, Ida

AU - Andersen, Marianne Agerholm

AU - Paulson, Joseph N.

AU - Treebak, Jonas Thue

AU - Sina, Christian

AU - Holm, Jacob Bak

AU - Kristiansen, Karsten

AU - Jensen, Benjamin Anderschou Holbech

PY - 2018/4

Y1 - 2018/4

N2 - Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined. We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters. Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly developed impaired glucose clearance followed by a gradual improvement from week 8 to week 39. All groups had similar responses to insulin 40 weeks post diet initiation despite severe nonalcoholic steatohepatitis in SOD-fed mice. We conclude that age-related alterations in glucose regulation may occur in both lean and obese mice and are modulated by dietary fat as indicated by the sustained metabolic homeostasis observed in mice fed ω3-polyunsaturated fatty acids.

AB - Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined. We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters. Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly developed impaired glucose clearance followed by a gradual improvement from week 8 to week 39. All groups had similar responses to insulin 40 weeks post diet initiation despite severe nonalcoholic steatohepatitis in SOD-fed mice. We conclude that age-related alterations in glucose regulation may occur in both lean and obese mice and are modulated by dietary fat as indicated by the sustained metabolic homeostasis observed in mice fed ω3-polyunsaturated fatty acids.

U2 - 10.1016/j.jnutbio.2017.09.026

DO - 10.1016/j.jnutbio.2017.09.026

M3 - Journal article

C2 - 29268121

SN - 0955-2863

VL - 54

SP - 66

EP - 76

JO - Journal of Nutritional Biochemistry

JF - Journal of Nutritional Biochemistry

ER -

Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat

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