Short Sleep Duration and Its Association with Obesity and Other Metabolic Risk Factors in Kuwaiti Urban Adults.

BACKGROUND: Efficient sleep duration and its quality are increasingly recognized as important contributors for maintaining normal body weight. However, lifestyle and social structure within the Arab-gulf region differ compared to those in the western world. This study was specifically conducted in Kuwait's population to investigate the link between sleep quality (SQ) and obesity in the absence of sleep apnea (SA) onset. METHODS: SQ was measured by the Pittsburgh Sleep Quality Index (PQSI) in 984 participants, then verified in 60 individuals including 20 lean (Body mass index/BMI: 18.5-24.9 kg/m2), 20 overweight (BMI: 25-29.9 kg/m2) and 20 obese (BMI: ≥30 kg/m2) through actigraph worn over the right-hip for 7 consecutive days to characterize their sleep-wake cycle, rest-activity, and physical activity. Blood samples were collected for metabolic markers. RESULTS: 59.6% of participants reported a PSQI score higher than 5, with 57.6% of the participants reporting less than 6 hours of sleep per day. The data show that both SQ and sleep duration are considered inadequate in comparison to the international SQ standards. We found a significant association between SQ and obesity independent of age and sex. Actigraph data further supported the independent association of sleep duration on BMI within the population (p < 0.001). Additionally, total sleep time (TST) was found to significantly correlate with several other metabolic factors including diastolic blood pressure, elevated resting heart rate (RHR), triglycerides, total cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), C-peptide, and C-Reactive Protein (CRP) secretion. Further multiple-regression analysis showed a significant independent association between blood pressure (p < 0.03), HOMA-IR (p < 0.04), and C-peptide (p < 0.3) and sleep duration. CONCLUSION: These findings suggest that sleep deprivation and disturbance could be indirect factors involved in the development of not only obesity in Kuwait but also other metabolic syndromes such as type 2 diabetes.

Elevated resting heart rate as a predictor of inflammation and cardiovascular risk in healthy obese individuals.

The role of leukocyte inflammatory markers and toll like receptors (TLRs)2/4 in pathologies associated with elevated resting heart rate (RHR) levels in healthy obese (HO) individuals is not well elucidated. Herein, we investigated the relationship of RHR with expression of leukocyte-inflammatory markers and TLRs in HO individuals. 58-obese and 57-lean participants with no history of a major medical condition, were recruited in this study. In HO individuals, the elevated-RHR correlated positively with diastolic blood pressure, cholesterol, pro-inflammatory monocytes CD11b+CD11c+CD206- phenotype (r = 0.52, P = 0.0003) as well as with activated T cells CD8+HLA-DR+ phenotype (r = 0.27, P = 0.039). No association was found between RHR and the percentage of CD16+CD11b+ neutrophils. Interestingly, elevated RHR positively correlated with cells expressing TLR4 and TLR2 (CD14+TLR4+, r = 0.51, P ≤ 0.0001; and CD14+TLR2+, r = 0.42, P = 0.001). TLR4+ expressing cells also associated positively with the plasma concentrations of proinflammatory or vascular permeability/matrix modulatory markers including TNF-α (r = 0.36, P = 0.005), VEGF (r = 0.47, P = 0.0002), and MMP-9 (r = 0.53, P ≤ 0.0001). Multiple regression revealed that RHR is independently associated with CD14+TLR4+ monocytes and VEGF. We conclude that in HO individuals, increased CD14+TLR4+ monocytes and circulatory VEGF levels associated independently with RHR, implying that RHR monitoring could be used as a non-invasive clinical indicator to identify healthy obese individuals at an increased risk of developing inflammation and cardiovascular disease.

Adipose tissue gene expression of CXCL10 and CXCL11 modulates inflammatory markers in obesity: implications for metabolic inflammation and insulin resistance.

BACKGROUND: The CXCL subfamily of chemokines (CXCL9, CXCL10, and CXCL11; angiostatic chemokines) plays a key role in many inflammatory diseases. However, the expression of CXCLs in adipose tissue (AT) during obesity and association of these CXCLs with inflammatory markers and insulin resistance are poorly understood. Therefore, this study aimed to investigate the effects of CXCL gene expression on subcutaneous AT inflammatory markers and insulin resistance. METHODS: Subcutaneous-fat biopsies were collected from 59 nondiabetic (lean/overweight/obese) individuals for RNA isolation. Expression levels of AT CXCL and inflammatory markers were determined by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Biomedical parameters in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). Insulin resistance was estimated using homeostatic model assessment (HOMA-IR). RESULTS: AT CXCL expression was higher in obese compared with lean individuals (p < 0.05) and positively correlated with body mass index (BMI; r ⩾ 0.269, p < 0.05). Expression of CXCL9, CXCL10, and CXCL11 correlated significantly with various pro-inflammatory markers, including family members of interleukins, chemokines, and their prospective receptors (r ⩾ 0.339, p ⩽ 0.009), but not anti-inflammatory markers. CXCL11 expression correlated specifically with the expression of CCL5, CCL18, TLR3, TLR4, TLR8, IRF5, and NF-κB (r ⩾ 0.279, p ⩽ 0.039). Notably, CXCL11 was correlated with C-reactive protein (CRP), fasting blood glucose (FBG), and HOMA-IR. In multiple regression analysis, CXCL11 was identified as an independent predictor of CCL19, CCL5, IL-6, and TLR3. CONCLUSION: These data suggest that the CXCL family members, specifically CXCL10 and CXCL11, are potential biomarkers for the onset of AT inflammation during obesity.

Increasing the Duration of Light Physical Activity Ameliorates Insulin Resistance Syndrome in Metabolically Healthy Obese Adults.

Obesity is a well-known risk factor for insulin resistance syndrome (IRS). Nevertheless, limited data are available regarding the effects of physical activity (PA) intensity on the ability to modulate IRS. The study aim was to investigate the beneficial effects of the longer duration of light PA vs. a single bout of the acute moderate or vigorous PA for improvement in IRS indicators. Sixty metabolically healthy obese (MHO) participants, 30 males and 30 females, with body mass index (BMI) of ≥30 were enrolled in this study. PA levels were measured using an accelerometer, and the expression of monocytic surface markers was analyzed using flow cytometry. Plasma cytokines' secretion was determined by enzyme-linked immunosorbent assay (ELISA). Univariate regression analysis evaluated the actigraphy-assessed PA measures, inflammatory cytokines, and insulin resistance. The longer duration of PA was found to be associated with the homeostatic model assessment of insulin resistance (HOMA-IR), a lower lipid profile, and the expression of inflammatory cytokines by monocytes. Even though, higher intensities of PA were found to be associated with lower body fat percentage, only the light intensity PA was found to be beneficial as it associated with the improved insulin sensitivity and lower expression of inflammatory markers. In conclusion, maintaining the longer duration of low-intensity PA throughout the day could be more beneficial for reducing inflammation and improving insulin resistance. This study supports a more feasible approach model to gain beneficial lifestyle changes for the prevention of IRS in metabolically healthy adults with obesity.

Stearic Acid and TNF-α Co-Operatively Potentiate MIP-1α Production in Monocytic Cells via MyD88 Independent TLR4/TBK/IRF3 Signaling Pathway.

Increased circulatory and adipose tissue expression of macrophage inflammatory protein (MIP)-1α (CC motif chemokine ligand-3/CCL3) and its association with inflammation in the state of obesity is well documented. Since obesity is associated with increases in both stearic acid and tumor necrosis factor α (TNF-α) in circulation, we investigated whether stearic acid and TNF-α together could regulate MIP-1α/CCL3 expression in human monocytic cells, and if so, which signaling pathways were involved in MIP-1α/CCL3 modulation. Monocytic cells were treated with stearic acid and TNF-α resulted in enhanced production of MIP-1α/CCL3 compared to stearic acid or TNF-α alone. To explore the underlying mechanisms, cooperative effect of stearic acid for MIP-α/CCL3 expression was reduced by TLR4 blocking, and unexpectedly we found that the synergistic production of MIP-α/CCL3 in MyD88 knockout (KO) cells was not suppressed. In contrast, this MIP-α/CCL3 expression was attenuated by inhibiting TBK1/IRF3 activity. Cells deficient in IRF3 did not show cooperative effect of stearate/TNF-α on MIP-1α/CCL3 production. Furthermore, activation of IRF3 by polyinosinic-polycytidylic acid (poly I:C) produced a cooperative effect with TNF-α for MIP-1α/CCL3 production that was comparable to stearic acid. Individuals with obesity show high IRF3 expression in monocytes as compared to lean individuals. Furthermore, elevated levels of MIP-1α/CCL3 positively correlate with TNF-α and CD163 in fat tissues from individuals with obesity. Taken together, this study provides a novel model for the pathologic role of stearic acid to produce MIP-1α/CCL3 in the presence of TNF-α associated with obesity settings.