Abstract
BackgroundThe effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown. In this study, we aimed to evaluate exercise capacity in mice fed with a high fat diet (HFD) for 3 days and investigate the molecular mechanisms in the early response to high-fat feeding.MethodsExercise capacity was assessed by weight-loaded swimming test in mice fed a control diet (10 kcal% fat) or a HFD (60 kcal% fat) for 3 days. Global gene expression of ten important tissues (brain, heart, liver, spleen, lung, kidney, stomach, duodenum, skeletal muscle and blood) was analyzed using RNA Sequencing.ResultsA HFD for just 3 days can induce 71% decrease of exercise performance prior to substantial weight gain (P <0.01). Principle component analysis revealed that differential gene expression patterns existed in the ten tissues. Out of which, the brain, spleen and lung were demonstrated to have more pronounced transcriptional changes than other tissues. Biological process analysis for differentially expressed genes in the brain, spleen and lung showed that dysregulation of peripheral and central immune response had been implicated in the early stage of HFD exposure. Neurotransmission related genes and circulatory system process related genes were significantly down-regulated in the brain and lung, respectively.ConclusionsOur findings provide new insights for the deleterious effects of high-fat feeding, especially revealing that the lung maybe as a new important target attacked by short-term high-fat feeding.
Highlights
The effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown
Our findings provide new insights for the deleterious effects of high-fat feeding, especially revealing that the lung maybe as a new important target attacked by short-term high-fat feeding
No differences were seen in plasma low-density lipoprotein-cholesterol (LDL-C), free fatty acids (FFAs) and apolipoprotein E (ApoE), the cholesterol level was significantly greater in the high fat diet (HFD)-fed mice (P < 0.001)
Summary
The effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown. We aimed to evaluate exercise capacity in mice fed with a high fat diet (HFD) for 3 days and investigate the molecular mechanisms in the early response to high-fat feeding. Studies in rats have demonstrated a beneficial effect of a fat-rich diet on exercise capacity via increasing the Advances in genomic technologies may help to reveal the early molecular changes by enabling simultaneous analysis of thousands of genes in response to a HFD. The transcriptomic analysis of duodenum mucosa after high-fat meal ingestion in C57BL/6 J mice found substantial changes of genes related to lipid metabolism [7]. Microarray analysis showed markedly changes of numerous genes involved in various biological processes including morphogenesis, fatty acid catabolism and amino acid metabolism following 3 days of high-fat feeding in the skeletal muscle of C57BL/6 J mice [8]. Microarray analysis showed markedly changes of numerous genes involved in various biological processes including morphogenesis, fatty acid catabolism and amino acid metabolism following 3 days of high-fat feeding in the skeletal muscle of C57BL/6 J mice [8]. cDNA microarrays analysis of mRNA expression showed downregulation of genes related to fatty acid biosynthesis in the liver of one week HFD-fed BALB/c mice [9]
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