Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models
TL;DR: In this paper, the authors reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM).
Abstract: The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.
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TL;DR: The authors explored changes in Rhesus macaques before and after sexual maturation based on multi-omics analysis and identified markers for determining sexual maturity, finding that sexually mature males have stronger sperm fertility and cholesterol metabolism compared to sexually immature males.
Abstract: Abstract Rhesus macaques ( Macaca mulatta , RMs) are widely used in sexual maturation studies due to their high genetic and physiological similarity to humans. However, judging sexual maturity in captive RMs based on blood physiological indicators, female menstruation, and male ejaculation behavior can be inaccurate. Here, we explored changes in RMs before and after sexual maturation based on multi-omics analysis and identified markers for determining sexual maturity. We found that differentially expressed microbiota, metabolites, and genes before and after sexual maturation showed many potential correlations. Specifically, genes involved in spermatogenesis ( TSSK2 , HSP90AA1 , S OX5 , SPAG16 , and SPATC1 ) were up-regulated in male macaques, and significant changes in gene ( CD36 ), metabolites (cholesterol, 7-ketolithocholic acid, and 12-ketolithocholic acid), and microbiota ( Lactobacillus ) related to cholesterol metabolism were also found, suggesting the sexually mature males have stronger sperm fertility and cholesterol metabolism compared to sexually immature males. In female macaques, most differences before and after sexual maturity were related to tryptophan metabolism, including changes in IDO1 , IDO2 , IFNGR2 , IL1Β , IL10 , L-tryptophan, kynurenic acid (KA), indole-3-acetic acid (IAA), indoleacetaldehyde, and Bifidobacteria , indicating that sexually mature females exhibit stronger neuromodulation and intestinal immunity than sexually immature females. Cholesterol metabolism-related changes ( CD36 , 7-ketolithocholic acid, 12-ketolithocholic acid) were also observed in female and male macaques. Exploring differences before and after sexual maturation through multi-omics, we identified potential biomarkers of sexual maturity in RMs, including Lactobacillus (for males) and Bifidobacterium (for females) valuable for RM breeding and sexual maturation research.
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TL;DR: The evolving concept of insulin resistance and T2D as having immunological components and an improving picture of how inflammation modulates metabolism provide new opportunities for using antiinflammatory strategies to correct the metabolic consequences of excess adiposity.
Abstract: Over a hundred years ago, high doses of salicylates were shown to lower glucose levels in diabetic patients. This should have been an important clue to link inflammation to the pathogenesis of type 2 diabetes (T2D), but the antihyperglycemic and antiinflammatory effects of salicylates were not connected to the pathogenesis of insulin resistance until recently. Together with the discovery of an important role for tissue macrophages, these new findings are helping to reshape thinking about how obesity increases the risk for developing T2D and the metabolic syndrome. The evolving concept of insulin resistance and T2D as having immunological components and an improving picture of how inflammation modulates metabolism provide new opportunities for using antiinflammatory strategies to correct the metabolic consequences of excess adiposity.
4,046 citations
TL;DR: Current understanding of the major factors regulating protein expression is summarized to demonstrate a substantial role for regulatory processes occurring after mRNA is made in controlling steady-state protein abundances.
Abstract: Recent advances in next-generation DNA sequencing and proteomics provide an unprecedented ability to survey mRNA and protein abundances. Such proteome-wide surveys are illuminating the extent to which different aspects of gene expression help to regulate cellular protein abundances. Current data demonstrate a substantial role for regulatory processes occurring after mRNA is made - that is, post-transcriptional, translational and protein degradation regulation - in controlling steady-state protein abundances. Intriguing observations are also emerging in relation to cells following perturbation, single-cell studies and the apparent evolutionary conservation of protein and mRNA abundances. Here, we summarize current understanding of the major factors regulating protein expression.
3,308 citations
TL;DR: It is concluded that transcript levels by themselves are not sufficient to predict protein levels in many scenarios and to thus explain genotype-phenotype relationships and that high-quality data quantifying different levels of gene expression are indispensable for the complete understanding of biological processes.
1,996 citations
TL;DR: An overview of available methods for the identification and quantification of free and ribosome‐bound mRNA, protein abundances and individual protein turnover rates is given.
1,574 citations
TL;DR: In this issue of the JCI, Gallagher and colleagues demonstrate that in diabetic mice, hyperoxia enhances the mobilization of circulating endothelial progenitor cells (EPCs) from the bone marrow to the peripheral circulation, resulting in accelerated wound healing.
Abstract: Diabetic foot ulcers (DFUs), a leading cause of amputations, affect 15% of people with diabetes. A series of multiple mechanisms, including decreased cell and growth factor response, lead to diminished peripheral blood flow and decreased local angiogenesis, all of which can contribute to lack of healing in persons with DFUs. In this issue of the JCI, Gallagher and colleagues demonstrate that in diabetic mice, hyperoxia enhances the mobilization of circulating endothelial progenitor cells (EPCs) from the bone marrow to the peripheral circulation (see the related article beginning on page 1249). Local injection of the chemokine stromal cell–derived factor–1α then recruits these EPCs to the cutaneous wound site, resulting in accelerated wound healing. Thus, Gallagher et al. have identified novel potential targets for therapeutic intervention in diabetic wound healing.
1,402 citations