Replacing Part of Glucose with Galactose in the Postweaning Diet Protects Female But Not Male Mice from High-Fat Diet-Induced Adiposity in Later Life

Lianne M.S. Bouwman, José M.S. Fernández-Calleja, Inge van der Stelt, Annemarie Oosting, Jaap Keijer, Evert M. van Schothorst

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Duration of breastfeeding is positively associated with decreased adiposity and increased metabolic health in later life, which might be related to galactose. OBJECTIVE: The aim of this study was to investigate if partial replacement of glucose with galactose in the postweaning diet had a metabolic programming effect. METHODS: Male and female mice (C57BL/6JRccHsd) received an isocaloric diet (16 energy% fat; 64 energy% carbohydrates; 20 energy% protein) with either glucose (32 energy%) (GLU) or glucose + galactose (GLU + GAL, 16 energy% each) for 3 wk postweaning. Afterwards, all mice were switched to the same 40 energy% high-fat diet (HFD) for 9 wk to evaluate potential programming effects in an obesogenic environment. Data were analyzed within sex. RESULTS: Female body weight (-14%) and fat mass (-47%) were significantly lower at the end of the HFD period (both P < 0.001) among those fed GLU + GAL than among those fed GLU; effects in males were in line with these findings but nonsignificant. Food intake was affected in GLU + GAL-fed females (+8% on postweaning diet, -9% on HFD) compared with GLU-fed females, but not for hypothalamic transcript levels at endpoint. Also, in GLU + GAL-fed females, serum insulin concentrations (-48%, P  < 0.05) and the associated homeostasis model assessment of insulin resistance (HOMA-IR) were significantly lower ( P < 0.05) at endpoint, but there were no changes in pancreas morphology. In GLU + GAL-fed females, expression of insulin receptor substrate 2 (Irs2) (-27%, P  < 0.01 ; -44%, P  < 0.001) and the adipocyte size markers leptin (Lep) (-40%, P  < 0.05; -63% , P  < 0.05) and mesoderm-specific transcript homolog protein (Mest) (-80%, P < 0.05; -72%, P  < 0.05) was lower in gonadal and subcutaneous white adipose tissue (WAT), respectively. Expression of insulin receptor substrate1 (Irs1) (-24%, P  < 0.05) was only lower in subcutaneous WAT in GLU + GAL-fed females. CONCLUSIONS: Partial replacement of glucose with galactose, resulting in a 1:1 ratio mimicking lactose, in a 3-wk postweaning diet lowered body weight, adiposity, HOMA-IR, and expression of WAT insulin signaling in HFD-challenged female mice in later life. This suggests that prolonged galactose intake may improve metabolic and overall health in later life.

LanguageEnglish
Pages1140-1148
Number of pages9
JournalThe Journal of Nutrition
Volume149
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

Fingerprint

Adiposity
High Fat Diet
Galactose
Diet
Glucose
White Adipose Tissue
Subcutaneous Fat
Insulin Resistance
Homeostasis
Body Weight
Insulin
Insulin Receptor Substrate Proteins
Insulin Receptor
Health
Lactose
Leptin
Breast Feeding
Inbred C57BL Mouse
Adipocytes
Adipose Tissue

Keywords

  • adipose tissue
  • galactose
  • insulin signaling
  • lactose
  • postweaning
  • programming

Cite this

@article{801acc80b8aa4f10842b59cee036e1e3,
title = "Replacing Part of Glucose with Galactose in the Postweaning Diet Protects Female But Not Male Mice from High-Fat Diet-Induced Adiposity in Later Life",
abstract = "BACKGROUND: Duration of breastfeeding is positively associated with decreased adiposity and increased metabolic health in later life, which might be related to galactose. OBJECTIVE: The aim of this study was to investigate if partial replacement of glucose with galactose in the postweaning diet had a metabolic programming effect. METHODS: Male and female mice (C57BL/6JRccHsd) received an isocaloric diet (16 energy{\%} fat; 64 energy{\%} carbohydrates; 20 energy{\%} protein) with either glucose (32 energy{\%}) (GLU) or glucose + galactose (GLU + GAL, 16 energy{\%} each) for 3 wk postweaning. Afterwards, all mice were switched to the same 40 energy{\%} high-fat diet (HFD) for 9 wk to evaluate potential programming effects in an obesogenic environment. Data were analyzed within sex. RESULTS: Female body weight (-14{\%}) and fat mass (-47{\%}) were significantly lower at the end of the HFD period (both P < 0.001) among those fed GLU + GAL than among those fed GLU; effects in males were in line with these findings but nonsignificant. Food intake was affected in GLU + GAL-fed females (+8{\%} on postweaning diet, -9{\%} on HFD) compared with GLU-fed females, but not for hypothalamic transcript levels at endpoint. Also, in GLU + GAL-fed females, serum insulin concentrations (-48{\%}, P  < 0.05) and the associated homeostasis model assessment of insulin resistance (HOMA-IR) were significantly lower ( P < 0.05) at endpoint, but there were no changes in pancreas morphology. In GLU + GAL-fed females, expression of insulin receptor substrate 2 (Irs2) (-27{\%}, P  < 0.01 ; -44{\%}, P  < 0.001) and the adipocyte size markers leptin (Lep) (-40{\%}, P  < 0.05; -63{\%} , P  < 0.05) and mesoderm-specific transcript homolog protein (Mest) (-80{\%}, P < 0.05; -72{\%}, P  < 0.05) was lower in gonadal and subcutaneous white adipose tissue (WAT), respectively. Expression of insulin receptor substrate1 (Irs1) (-24{\%}, P  < 0.05) was only lower in subcutaneous WAT in GLU + GAL-fed females. CONCLUSIONS: Partial replacement of glucose with galactose, resulting in a 1:1 ratio mimicking lactose, in a 3-wk postweaning diet lowered body weight, adiposity, HOMA-IR, and expression of WAT insulin signaling in HFD-challenged female mice in later life. This suggests that prolonged galactose intake may improve metabolic and overall health in later life.",
keywords = "adipose tissue, galactose, insulin signaling, lactose, postweaning, programming",
author = "Bouwman, {Lianne M.S.} and Fern{\'a}ndez-Calleja, {Jos{\'e} M.S.} and {van der Stelt}, Inge and Annemarie Oosting and Jaap Keijer and {van Schothorst}, {Evert M.}",
year = "2019",
month = "7",
day = "1",
doi = "10.1093/jn/nxz028",
language = "English",
volume = "149",
pages = "1140--1148",
journal = "The Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "7",

}

Replacing Part of Glucose with Galactose in the Postweaning Diet Protects Female But Not Male Mice from High-Fat Diet-Induced Adiposity in Later Life. / Bouwman, Lianne M.S.; Fernández-Calleja, José M.S.; van der Stelt, Inge; Oosting, Annemarie; Keijer, Jaap; van Schothorst, Evert M.

In: The Journal of Nutrition, Vol. 149, No. 7, 01.07.2019, p. 1140-1148.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Replacing Part of Glucose with Galactose in the Postweaning Diet Protects Female But Not Male Mice from High-Fat Diet-Induced Adiposity in Later Life

AU - Bouwman, Lianne M.S.

AU - Fernández-Calleja, José M.S.

AU - van der Stelt, Inge

AU - Oosting, Annemarie

AU - Keijer, Jaap

AU - van Schothorst, Evert M.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - BACKGROUND: Duration of breastfeeding is positively associated with decreased adiposity and increased metabolic health in later life, which might be related to galactose. OBJECTIVE: The aim of this study was to investigate if partial replacement of glucose with galactose in the postweaning diet had a metabolic programming effect. METHODS: Male and female mice (C57BL/6JRccHsd) received an isocaloric diet (16 energy% fat; 64 energy% carbohydrates; 20 energy% protein) with either glucose (32 energy%) (GLU) or glucose + galactose (GLU + GAL, 16 energy% each) for 3 wk postweaning. Afterwards, all mice were switched to the same 40 energy% high-fat diet (HFD) for 9 wk to evaluate potential programming effects in an obesogenic environment. Data were analyzed within sex. RESULTS: Female body weight (-14%) and fat mass (-47%) were significantly lower at the end of the HFD period (both P < 0.001) among those fed GLU + GAL than among those fed GLU; effects in males were in line with these findings but nonsignificant. Food intake was affected in GLU + GAL-fed females (+8% on postweaning diet, -9% on HFD) compared with GLU-fed females, but not for hypothalamic transcript levels at endpoint. Also, in GLU + GAL-fed females, serum insulin concentrations (-48%, P  < 0.05) and the associated homeostasis model assessment of insulin resistance (HOMA-IR) were significantly lower ( P < 0.05) at endpoint, but there were no changes in pancreas morphology. In GLU + GAL-fed females, expression of insulin receptor substrate 2 (Irs2) (-27%, P  < 0.01 ; -44%, P  < 0.001) and the adipocyte size markers leptin (Lep) (-40%, P  < 0.05; -63% , P  < 0.05) and mesoderm-specific transcript homolog protein (Mest) (-80%, P < 0.05; -72%, P  < 0.05) was lower in gonadal and subcutaneous white adipose tissue (WAT), respectively. Expression of insulin receptor substrate1 (Irs1) (-24%, P  < 0.05) was only lower in subcutaneous WAT in GLU + GAL-fed females. CONCLUSIONS: Partial replacement of glucose with galactose, resulting in a 1:1 ratio mimicking lactose, in a 3-wk postweaning diet lowered body weight, adiposity, HOMA-IR, and expression of WAT insulin signaling in HFD-challenged female mice in later life. This suggests that prolonged galactose intake may improve metabolic and overall health in later life.

AB - BACKGROUND: Duration of breastfeeding is positively associated with decreased adiposity and increased metabolic health in later life, which might be related to galactose. OBJECTIVE: The aim of this study was to investigate if partial replacement of glucose with galactose in the postweaning diet had a metabolic programming effect. METHODS: Male and female mice (C57BL/6JRccHsd) received an isocaloric diet (16 energy% fat; 64 energy% carbohydrates; 20 energy% protein) with either glucose (32 energy%) (GLU) or glucose + galactose (GLU + GAL, 16 energy% each) for 3 wk postweaning. Afterwards, all mice were switched to the same 40 energy% high-fat diet (HFD) for 9 wk to evaluate potential programming effects in an obesogenic environment. Data were analyzed within sex. RESULTS: Female body weight (-14%) and fat mass (-47%) were significantly lower at the end of the HFD period (both P < 0.001) among those fed GLU + GAL than among those fed GLU; effects in males were in line with these findings but nonsignificant. Food intake was affected in GLU + GAL-fed females (+8% on postweaning diet, -9% on HFD) compared with GLU-fed females, but not for hypothalamic transcript levels at endpoint. Also, in GLU + GAL-fed females, serum insulin concentrations (-48%, P  < 0.05) and the associated homeostasis model assessment of insulin resistance (HOMA-IR) were significantly lower ( P < 0.05) at endpoint, but there were no changes in pancreas morphology. In GLU + GAL-fed females, expression of insulin receptor substrate 2 (Irs2) (-27%, P  < 0.01 ; -44%, P  < 0.001) and the adipocyte size markers leptin (Lep) (-40%, P  < 0.05; -63% , P  < 0.05) and mesoderm-specific transcript homolog protein (Mest) (-80%, P < 0.05; -72%, P  < 0.05) was lower in gonadal and subcutaneous white adipose tissue (WAT), respectively. Expression of insulin receptor substrate1 (Irs1) (-24%, P  < 0.05) was only lower in subcutaneous WAT in GLU + GAL-fed females. CONCLUSIONS: Partial replacement of glucose with galactose, resulting in a 1:1 ratio mimicking lactose, in a 3-wk postweaning diet lowered body weight, adiposity, HOMA-IR, and expression of WAT insulin signaling in HFD-challenged female mice in later life. This suggests that prolonged galactose intake may improve metabolic and overall health in later life.

KW - adipose tissue

KW - galactose

KW - insulin signaling

KW - lactose

KW - postweaning

KW - programming

U2 - 10.1093/jn/nxz028

DO - 10.1093/jn/nxz028

M3 - Article

VL - 149

SP - 1140

EP - 1148

JO - The Journal of Nutrition

T2 - The Journal of Nutrition

JF - The Journal of Nutrition

SN - 0022-3166

IS - 7

ER -