Cardiometabolic diseases, which include obesity, diabetes, hypertension and cardiovascular disease, are associated with reduced quality of life and reduced life expectancy. Unfortunately, racial/ethnic and socioeconomic disparities in these diseases exist such that minority populations, such as African Americans and Hispanics, and those of lower socioeconomic status, experience a greater burden. Several reports have indicated that there are differences in sleep duration and quality that mirror the disparities in cardiometabolic disease. The goal of this paper is to review the association between sleep and cardiometabolic disease risk because of the possibility that suboptimal sleep may partially mediate the cardiometabolic disease disparities. We will review both experimental studies that have restricted sleep duration or impaired sleep quality and examined biomarkers of cardiometabolic disease risk, including glucose metabolism and insulin sensitivity, appetite regulation and food intake, and immune function. We will also review observational studies that have examined the association between habitual sleep duration and quality and the prevalence or risk of obesity, diabetes, hypertension and cardiovascular disease. Many experimental and observational studies do support an association between suboptimal sleep and increased cardiometabolic disease risk.

A hallmark of biology is the cyclical nature of organismal physiology driven by networks of biological, including circadian, rhythms. Unsurprisingly, disruptions of the circadian rhythms through sleep curtailment or shift work have been connected through numerous studies to positive associations with obesity, insulin resistance, and diabetes. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) measures oscillation in messenger RNA expression, an essential foundation for the study of the physiological circadian regulatory network. Primarily, measured oscillations have involved the use of reference gene normalization. However, the validation and identification of suitable reference genes is a significant challenge across different biological systems. This study focuses on adipose tissue of premenopausal, otherwise healthy, morbidly obese women voluntarily enrolled after being scheduled for laparoscopic sleeve gastrectomy surgery. Acquisition of tissue was accomplished by aspiratory needle biopsies of subcutaneous adipose tissue 1 to 2 weeks prior to surgery and 12 to 13 weeks following surgery and an in-surgery scalpel-assisted excision of mesenteric adipose tissue. Each biopsy was sterile cultured ex vivo and serially collected every 4 h over approximately 36 h. The candidate reference genes that were tested were 18S rRNA, GAPDH, HPRT1, RPII, RPL13α, and YWHAZ. Three analytic tools were used to test suitability, and the candidate reference genes were used to measure oscillation in expression of a known circadian clock element (Dbp). No gene was deemed suitable as an individual reference gene control, which indicated that the optimal reference gene set was the geometrically averaged 3-gene panel composed of YWHAZ, RPL13α, and GAPDH. These methods can be employed to identify optimal reference genes in other systems.

In addition to the caloric and macronutrient composition of meals, timing of energy consumption may be important for optimal glucose metabolism. Our goal was to examine whether the habitual timing of energy intake was associated with insulin sensitivity in healthy volunteers. Volunteers without diabetes aged 21–50 years completed a 3-day food diary and underwent an oral glucose tolerance test to estimate insulin sensitivity (n = 44). From the food diary, we calculated the proportions of the total energy and macronutrients consumed in the morning and evening, and the clock time at which 25%, 50% and 75% of total energy was consumed. A greater proportion of energy intake in the morning was significantly associated with higher insulin sensitivity estimated by Matsuda Index (B = 2.8 per 10%; 95%CI: 0.3, 5.2). The time at which 25% of energy was consumed was associated with insulin sensitivity estimated by Matsuda Index (B = −1.6 per hour; 95%CI: −3.0, −0.3) and QUICKI (B = −1.4 per hour, 95%CI: −2.8, −0.1). The timing of carbohydrate consumption demonstrated similar associations. Greater energy intake earlier in the day was associated with higher insulin sensitivity in individuals without diabetes.

Extracellular circulating miRNAs (ECmiRNAs) play a crucial role in cell-to-cell communication and serve as non-invasive biomarkers in a wide range of diseases, but their abundance and functional relevance in cystic fibrosis (CF) remain poorly understood. In this study, we employed microarray technology to identify aberrantly expressed plasma ECmiRNAs in CF and elucidate the functional relevance of their targets. Overall, we captured several ECmiRNAs abundantly expressed in CF. Expression levels of 11 ECmiRNAs differed significantly between CF and healthy control (HC) samples (FDR < 0.05, log2 FC≥2). Among these, 10 were overexpressed while only hsa-miR-598-3p was underexpressed in CF. The overexpressed miRNAs included three let-7 family members (hsa-let-7b-5p, hsa-let-7c-5p and hsa-let-7d-5p), three 103/107 family members (hsa-mir-103a-3p; hsa-mir-103b; hsa-mir-107), hsa-miR-486-5p, and other miRNAs. Using in silico methods, we identified 2,505 validated targets of the 11 differentially expressed miRNAs. Hsa-let-7b-5p was the most important hub in the network analysis. The top-ranked validated targets were involved in miRNA biogenesis and gene expression, including AGO1, DICER1, HMGA1, and MYC. The top pathways influenced by all targets were primarily signal transduction pathways associated with CF, including PI3K/Akt-, Wnt/β catenin-, glucocorticoid receptor-, and mTor signaling pathways. Our results suggest ECmiRNAs may be clinically relevant in CF and warrant further study.

Background In cystic fibrosis (CF), impaired immune cell responses, driven by the dysfunctional CF transmembrane conductance regulator ( CFTR ) gene, may determine the disease severity but clinical heterogeneity remains a major therapeutic challenge. The characterization of molecular mechanisms underlying impaired immune responses in CF may reveal novel targets with therapeutic potential. Therefore, we utilized simultaneous RNA sequencing targeted at identifying differentially expressed genes, transcripts, and miRNAs that characterize impaired immune responses triggered by CF and its phenotypes. Methods Peripheral blood mononuclear cells (PBMCs) extracted from a healthy donor were stimulated with plasma from CF patients ( n = 9) and healthy controls ( n = 3). The PBMCs were cultured (1 × 10 5 cells/well) for 9 h at 37 ° C in 5% CO 2 . After culture, total RNA was extracted from each sample and used for simultaneous total RNA and miRNA sequencing. Results Analysis of expression signatures from peripheral blood mononuclear cells induced by plasma of CF patients and healthy controls identified 151 genes, 154 individual transcripts, and 41 miRNAs differentially expressed in CF compared to HC while the expression signatures of 285 genes, 241 individual transcripts, and seven miRNAs differed due to CF phenotypes. Top immune pathways influenced by CF included agranulocyte adhesion, diapedesis signaling, and IL17 signaling, while those influenced by CF phenotypes included natural killer cell signaling and PI3K signaling in B lymphocytes. Upstream regulator analysis indicated dysregulation of CCL5, NF-κB and IL1A due to CF while dysregulation of TREM1 and TP53 regulators were associated with CF phenotype. Five miRNAs showed inverse expression patterns with three target genes relevant in CF-associated impaired immune pathways while two miRNAs showed inverse expression patterns with two target genes relevant to a dysregulated immune pathway associated with CF phenotypes. Conclusions Our results indicate that miRNAs and individual transcript variants are relevant molecular targets contributing to impaired immune cell responses in CF. Electronic supplementary material The online version of this article (10.1186/s12920-019-0529-0) contains supplementary material, which is available to authorized users.