High-Fructose/High-Fat Diet Downregulates the Hepatic Mitochondrial Oxidative Phosphorylation Pathway in Mice Compared with High-Fat Diet Alone

Milton D Chiang Morales; Chao-Yuan Chang; Van Long Le; I-Tao Huang; I-Lin Tsai; Hung-Jen Shih; Chun-Jen Huang

doi:10.3390/cells11213425

High-Fructose/High-Fat Diet Downregulates the Hepatic Mitochondrial Oxidative Phosphorylation Pathway in Mice Compared with High-Fat Diet Alone

Cells. 2022 Oct 29;11(21):3425. doi: 10.3390/cells11213425.

Authors

Milton D Chiang Morales^{1

2}, Chao-Yuan Chang^{2

3

4}, Van Long Le^{1

5}, I-Tao Huang^{6

7}, I-Lin Tsai⁸, Hung-Jen Shih^{9

10}, Chun-Jen Huang^{2

4

11

12}

Affiliations

¹ International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
² Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
³ Department of Medical Research, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
⁴ Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
⁵ Department of Anesthesiology and Critical Care, Hue University of Medicine and Pharmacy, Hue City 52000, Vietnam.
⁶ Emergency Department, Redcliffe Hospital, Redcliffe, QLD 4020, Australia.
⁷ School of Public Health, Faculty of Medicine, University of Queensland, Herston, QLD 4006, Australia.
⁸ Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
⁹ Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
¹⁰ Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
¹¹ Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
¹² Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Abstract

Both high-fat diet (HFD) alone and high-fructose plus HFD (HFr/HFD) cause diet-induced non-alcoholic fatty liver disease in murine models. However, the mechanisms underlying their impacts on inducing different levels of liver injury are yet to be elucidated. This study employed a proteomic approach to elucidate further on this issue. Adult male C57BL/6J mice were allocated to the HFD or the HFr/HFD group. After feeding for 12 weeks, all mice were euthanized and samples were collected. The proteomic profiles in liver tissues were analyzed using liquid chromatography-tandem mass spectrometry followed by canonical pathway analysis. We demonstrated that the mitochondrial oxidative phosphorylation (OXPHOS) pathway was the most significantly downregulated canonical pathway in the HFr/HFD group when compared with the HFD group. Within the OXPHOS pathway, the HFr/HFD group demonstrated significant downregulation of complexes I and III and significant upregulation of complex IV when compared with the HFD group. Moreover, the HFr/HFD group had lower protein levels of NADH: ubiquinone oxidoreductase subunits S3, S6, A5, and A12 in complex I (p < 0.001, =0.03, <0.001, and <0.001, respectively), lower protein level of cytochrome C in complex III (p < 0.001), and higher protein level of cytochrome C oxidase subunit 2 in complex IV (p = 0.002), when compared with the HFD group. To summarize, we have demonstrated that the hepatic mitochondrial OXPHOS pathway is significantly downregulated in long-term HFr/HFD feeding when compared with long-term HFD feeding. These data support the concept that the hepatic mitochondrial OXPHOS pathway should be involved in mediating the effects of HFr/HFD on inducing more severe liver injury than HFD alone.

Keywords: OXPHOS; high fructose; high-fat diet; liver; mitochondria; proteomic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diet, High-Fat* / adverse effects
Fructose* / metabolism
Liver / metabolism
Male
Mice
Mice, Inbred C57BL
Oxidative Phosphorylation
Proteomics

Substances

Fructose

Grants and funding

This research was funded by the Ministry of Science and Technology, Taiwan (grant numbers: MOST 110-2314-B-038-103-MY2 to Chun-Jen Huang; MOST 111-2314-B-038-127-MY2 to Chao-Yuan Chang) and Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (grant number: 111-wf-eva-12 to Chun-Jen Huang; 111-wf-eva-16 to Chao-Yuan Chang).