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Toxicologic Pathology
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Articles

The Effect of Fasting on Hepatic Lipid Accumulation and Transcriptional Regulation of Lipid Metabolism Differs between C57BL/6J and BALB/cA Mice Fed a High-fat Diet

Satomi Nishikawa
Kunio Doi
Hiroyuki Nakayama
Koji Uetsuka

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

Correspondence: Koji Uetsuka, Nippon Institute for Biological Science, 9-2221-1, Shin-Machi, Ome, Tokyo 198-0024, Japan; e-mail:koji_ue{at}nibs.or.jp.

The effects of fasting on hepatic lipid metabolism in mice fed a high-fat diet (HFD) are still unclear. After fasting, the degree of hepatic lipid accumulation differs between HFD-fed C57BL/6J (B6) and BALB/cA (BALB/c) mice. It is not clear whether this difference is due to sensitivity to fasting or HFD. The aim of this study is to elucidate this difference among strains. After nine weeks of HFD feeding, both B6 and BALB/c mice showed moderate hepatic steatosis. However, after a subsequent twenty-hour fast, the hepatic lipid accumulation was markedly decreased in B6 but not in BALB/c mice. Moreover, the mRNA expression of a transcription factor, Srebp1(regulates hepatic lipid metabolism), and its target genes—malic enzyme, acetyl-CoA carboxylase, fatty acid synthase(regulate fatty acid synthesis), and glycerol-3-phosphate acyltransferase(regulates triacylglycerol synthesis)—were more markedly reduced in B6 than BALB/c mice. In conclusion, fasting may modify hepatic lipid accumulation in HFD-fed B6 and BALB/c mice differently. The difference may be partly owing to a marked downregulation of the expression of some lipid-metabolism–related genes in B6 mice. These results suggest that fasting per se has a significant effect on hepatic lipid accumulation in mouse strains. SREBP1 might play a role in this fasting effect.

Key Words: fasting • fatty liver • mice • inbred strain • lipid metabolism

Abbreviations: ACSs, acyl-coA synthetases • BALB/c, BALB/cA • B6, C57BL/6J • GAPDH, glyceraldehyde-3-phosphate dehydrogenase • HE, hematoxylin and eosin • HFD, high-fat diet • SD, standard deviation • Srebp1, sterol regulatory element binding protein 1 • TAG, triacylglycerol • VLDL, very-low density lipoprotein

This version was published on October 1, 2008

Toxicologic Pathology, Vol. 36, No. 6, 850-857 (2008)
DOI: 10.1177/0192623308323920
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