Transcriptomic insights into the lipotoxicity of high-fat high-fructose diet in rat and mouse

• Published in: The Journal of nutritional biochemistry 2024-06, Vol.128, p.109626, Article 109626
• Main Authors: Zhu, An-Qi, Luo, Ning, Zhou, Xiao-Ting, Yuan, Min, Zhang, Chu-Mei, Pan, Tian-Ling, Li, Kun-Ping
• Format: Article
• Language: English
• Subjects: ACSL1-CPT1A-CPT2 pathway; Animals; Comparative transcriptomics analysis; de novo lipogenesis; Diet, High-Fat - adverse effects; Fatty Acid Synthase, Type I; Fatty Acids - metabolism; Fructose - adverse effects; High-fat high-fructose diet; Lipogenesis; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Obesity - metabolism; Rats; Rats, Sprague-Dawley; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Transcriptome
• ISSN: 0955-2863; 1873-4847; 1873-4847
• DOI: 10.1016/j.jnutbio.2024.109626

Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids β-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet. Overconsumption of HFF diet unbalances the energy intake and expenditure and usually leads to obesity and associated complications. Different kinds of high-calorie diet fed rats/mice manifest distinct hepatic transcriptome and the underlying ingenious regulatory mechanisms remain unclear. Downregulation of some key proteins (SREBP1, FASN) involved in de novo lipogenesis and ACSL1-CPT1A-CPT2 pathway positively mediate the metabolic adaptation to HFF. [Display omitted]