Multi-omics analysis of the effects of dietary changes and probiotics on diet-induced obesity

Obesity in adolescence is increasing in frequency and is associated with elevated proinflammatory cytokines and chronic pain in a sex-dependent manner. Dietary probiotics may mitigate these detrimental effects of obesity. Using a Long-Evans adolescent and adult rat model of overweight (high fat diet - 45% kcal from fat from weaning; HFD), we determined the effect of a single strain dietary probiotic (L. plantarum 299v [Lp299v] from weaning) on the theoretically increased neuropathic injury-induced pain phenotype and inflammatory cytokines. We found that although HFD increased fat mass, it did not markedly affect pain phenotype, particularly in adolescence, but there were subtle differences in pain in adult male vs. female rats. The combination of HFD and Lp299v augmented the increase in leptin in adolescent females. There were many non-interacting, main effects of age, diet and probiotic on an array of cytokines and adipokines with adults being higher than adolescents, HFD higher than the control diet, and a decrease with probiotic compared to placebo. Of particular interest were the probiotic-induced increases in IL12p70 in female adolescents on a HFD. We conclude that a more striking pain phenotype could require a higher and longer duration caloric diet or different etiology of pain. A major strength of our study was that a single strain probiotic had a wide range of inhibiting effects on most pro-inflammatory cytokines. The positive effect of probiotic on leptin in female adolescent rats is intriguing and worthy of exploration.

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A comprehensive multiomics approach reveals that high levels of sphingolipids in cardiac cachexia adipose tissue are associated with inflammatory and fibrotic changes

Qu,

Wang,

et al. 2023

Lipids Health Dis

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Cardiac cachexia is a deadly consequence of advanced heart failure that is characterised by the dysregulation of adipose tissue homeostasis. Once cachexia occurs with heart failure, it prevents the normal treatment of heart failure and increases the risk of death. Targeting adipose tissue is an important approach to treating cardiac cachexia, but the pathogenic mechanisms are still unknown, and there are no effective therapies available. Transcriptomics, metabolomics, and lipidomics were used to examine the underlying mechanisms of cardiac cachexia. Transcriptomics investigation of cardiac cachexia adipose tissue revealed that genes involved in fibrosis and monocyte/macrophage migration were increased and strongly interacted. The ECM-receptor interaction pathway was primarily enriched, as shown by KEGG enrichment analysis. In addition, gene set enrichment analysis revealed that monocyte chemotaxis/macrophage migration and fibrosis gene sets were upregulated in cardiac cachexia. Metabolomics enrichment analysis demonstrated that the sphingolipid signalling pathway is important for adipose tissue remodelling in cardiac cachexia. Lipidomics analysis showed that the adipose tissue of rats with cardiac cachexia had higher levels of sphingolipids, including Cer and S1P. Moreover, combined multiomics analysis suggested that the sphingolipid metabolic pathway was associated with inflammatory-fibrotic changes in adipose tissue. Finally, the key indicators were validated by experiments. In conclusion, this study described a mechanism by which the sphingolipid signalling pathway was involved in adipose tissue remodelling by inducing inflammation and fat fibrosis in cardiac cachexia.

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Multi-omics analysis of the effects of dietary changes and probiotics on diet-induced obesity

Cited by 4 publications

References 62 publications

Omics Technologies in Drug Discovery and Therapeutics

Omics Technologies in Drug Discovery and Therapeutics

Probiotic and high-fat diet: effects on pain assessment, body composition, and cytokines in male and female adolescent and adult rats

A comprehensive multiomics approach reveals that high levels of sphingolipids in cardiac cachexia adipose tissue are associated with inflammatory and fibrotic changes

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