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High-protein diet alleviate cardiac damage, adipose tissue inflammation, and alterations in the gut microbiota induced by chronic sleep fragmentation

ABSTRACT: Background: Sleep is fundamental to growth, immune function, and overall health. We initiate our study to elucidate the impact of sleep fragmentation (SF) on the cardiac function, gut microbiome diversity, and the transcriptomic profile of inguinal white adipose tissue (iWAT) in mice, as well as the regulatory role of a high protein diet. Methods: We constructed chronic SF and high protein diet intervention mouse models for this research. Cardiac structure and function were evaluated by echocardiographic analyses. Gut microbiota composition was determined by 16s rDNA amplicon sequencing. Transcriptome alterations of iWAT were assessed by RNA-sequencing. Results: Our result revealed that SF interventions induced inflammatory changes in adipose tissue and perturbed the diversity and composition of the gut microbiota. Concurrently, 6-week SF intervention led to a significant decline in left ventricular systolic function in mice, manifested by a notable decrease in EF and FS. Masson staining revealed distinctions compared to the control group, suggesting an increase in myocardial collagen fiber content following SF intervention. High-protein diet intervention partially mitigated the damage to cardiac structure and function caused by SF. Meanwhile, high-protein diet coupled with improvements in the adipose tissue transcriptome changes induced by SF. Conclusions: In conclusion, chronic SF intervention induced cardiac damage, alters gut microbiota composition and induce adipose tissue inflammation. High-protein diet could partially mitigate the changes above.

ORGANISM(S): Mus musculus

PROVIDER: GSE262679 | GEO | 2026/03/31

REPOSITORIES: GEO

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Project description:We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis. Keywords: Diet intervention study Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.

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High-protein diet alleviate cardiac damage, adipose tissue inflammation, and alterations in the gut microbiota induced by chronic sleep fragmentation

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