Elsevier

The Journal of Nutrition

Volume 146, Issue 2, February 2016, Pages 184-190
The Journal of Nutrition

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 Diet123

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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/6 male mice were fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either 4% or 13.5% of energy for 5 wk (Expt. 1) or 1 wk (Expt. 2). In Expt. 3, mice were 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.

Keywords

fibroblast growth factor
high-carbohydrate diet
high-fat diet
steatosis
exercise

Abbreviations

ACC1
acetyl-CoA carboxylase 1
FAS
fatty acid synthase
FGF21
fibroblast growth factor 21
GLUT1
glucose transporter 1
HC
high-carbohydrate
HFD
high-fat diet
LE
lipid emulsion
LFD
low-fat diet
SFP
standard feed pellet
SREBPF1
sterol-response element binding protein 1C

Cited by (0)

1

Supported by funds from the Graduate Program in Nutrition, Graduate Program in Food Science, Dorothy Foehr Huck Chair (ACR), and NIH grants CA90214 (ACR) and AT004678 (JDL). Baxter Healthcare Corporation provided the liquid diet (Clinimix E), vitamins, and lipid emulsion (Intralipid) used in studies 1 and 2. A postdoctoral research award from Baxter to the Department of Nutritional Sciences partially supported KI.

2

Author disclosures: L Hao, K-H Huang, K Ito, S Sae-tan, JD Lambert, and AC Ross, no conflicts of interest.

3

Supplemental Tables 1 and 2 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org.

7

Present address: Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129.

8

Present address: Department of Medicine, Jikei University, Tokyo, Japan.

9

Present address: Department of Food Science and Technology, Faculty of Agro-Industry, Kasetsart University, Bangkok, Thailand.

10

These authors contributed equally to this work.