Fibroblast growth factor 21 (FGF21) gene expression is elevated in the liver of mice fed a high-carbohydrate liquid diet and attenuated by a lipid emulsion but is not upregulated in the liver of mice fed a high-fat obesogenic diet

Lei Hao, Kuan Hsun Huang, Kyoko Ito, Sudathip Sae-Tan, Joshua D. Lambert, A. Catharine Ross

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Abstract

Background: Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. Objective: We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. Methods: C57BL/6malemicewere fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either4%or 13.5%of energy for 5 wk (Expt. 1) or 1wk (Expt. 2). In Expt. 3,micewere fed a purified LFD (~10% fat) or HFD (~60% fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. Results: Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5-to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+ exercise group to <20% of the level in the HFD group (P < 0.0001). Conclusions: In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake.

Original languageEnglish (US)
Pages (from-to)184-190
Number of pages7
JournalJournal of Nutrition
Volume146
Issue number2
DOIs
StatePublished - Jan 1 2016

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High Fat Diet
Emulsions
Carbohydrates
Diet
Lipids
Gene Expression
Liver
Fat-Restricted Diet
Fats
Gene Expression Regulation
Messenger RNA
Carbohydrate Metabolism
fibroblast growth factor 21
Lipid Metabolism
Running
Blood Proteins
Proteins
Glucose

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

@article{99eba32f69de45ddbb1387033b3e300c,
title = "Fibroblast growth factor 21 (FGF21) gene expression is elevated in the liver of mice fed a high-carbohydrate liquid diet and attenuated by a lipid emulsion but is not upregulated in the liver of mice fed a high-fat obesogenic diet",
abstract = "Background: Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. Objective: We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. Methods: C57BL/6malemicewere fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either4{\%}or 13.5{\%}of energy for 5 wk (Expt. 1) or 1wk (Expt. 2). In Expt. 3,micewere fed a purified LFD (~10{\%} fat) or HFD (~60{\%} fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. Results: Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5-to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+ exercise group to <20{\%} of the level in the HFD group (P < 0.0001). Conclusions: In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake.",
author = "Lei Hao and Huang, {Kuan Hsun} and Kyoko Ito and Sudathip Sae-Tan and Lambert, {Joshua D.} and Ross, {A. Catharine}",
year = "2016",
month = "1",
day = "1",
doi = "10.3945/jn.115.216572",
language = "English (US)",
volume = "146",
pages = "184--190",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "2",

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TY - JOUR

T1 - Fibroblast growth factor 21 (FGF21) gene expression is elevated in the liver of mice fed a high-carbohydrate liquid diet and attenuated by a lipid emulsion but is not upregulated in the liver of mice fed a high-fat obesogenic diet

AU - Hao, Lei

AU - Huang, Kuan Hsun

AU - Ito, Kyoko

AU - Sae-Tan, Sudathip

AU - Lambert, Joshua D.

AU - Ross, A. Catharine

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. Objective: We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. Methods: C57BL/6malemicewere fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either4%or 13.5%of energy for 5 wk (Expt. 1) or 1wk (Expt. 2). In Expt. 3,micewere fed a purified LFD (~10% fat) or HFD (~60% fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. Results: Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5-to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+ exercise group to <20% of the level in the HFD group (P < 0.0001). Conclusions: In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake.

AB - Background: Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. Objective: We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. Methods: C57BL/6malemicewere fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either4%or 13.5%of energy for 5 wk (Expt. 1) or 1wk (Expt. 2). In Expt. 3,micewere fed a purified LFD (~10% fat) or HFD (~60% fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. Results: Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5-to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+ exercise group to <20% of the level in the HFD group (P < 0.0001). Conclusions: In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake.

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