Objective:Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate... Show moreObjective:Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate the association between HTGC and coagulation factors (F)I (fibrinogen), VIII, IX, and XI while adjusting for TBF and VAT.Approach and Results:In this cross-sectional analysis of the NEO study (Netherlands Epidemiology of Obesity; n=6671), a random subset of participants underwent magnetic resonance imaging and magnetic resonance spectroscopy to assess VAT and HTGC (n=2580). We excluded participants without complete imaging and coagulation assessment, and with history of liver disease, venous thrombosis, or on anticoagulation. Mean differences in coagulation factor levels across HTGC quartiles were estimated by linear regression adjusted for age, sex, ethnicity, education, alcohol intake, physical activity, smoking, estrogen, and menopause, in addition to TBF and VAT. Among the 1946 participants included, median HTGC was 2.66% (interquartile range: 1.34%-6.27%). Coagulation factor levels increased dose-dependently across HTGC quartiles. Mean differences between the fourth and first quartiles were 14.7 mg/dL (95% CI, 2.1-27.2) for fibrinogen, 6.7 IU/dL (95% CI, 0.5-12.9) for FVIII, 26.1 IU/dL (95% CI, 22.4-29.8) for FIX, and 8.6 IU/dL (95% CI, 4.6-12.6) for FXI. With further adjustment for TBF and VAT, the dose-response association of HTGC with FIX persisted, whereas associations with other factors disappeared.Conclusions:HTGC was associated with various coagulation factors, of which FIX remained associated with HTGC after adjustment for TBF and VAT. HTGC might contribute to venous thrombosis risk beyond total body and visceral fat through FIX levels. Show less
Background: COVID-19 is a global challenge to healthcare. Obesity is common in patients with COVID-19 and seems to aggravate disease prognosis. In this review we explore the link between obesity,... Show moreBackground: COVID-19 is a global challenge to healthcare. Obesity is common in patients with COVID-19 and seems to aggravate disease prognosis. In this review we explore the link between obesity, chronic disease, lifestyle factors and the immune system, and propose societal interventions to enhance global immunity.Search Strategy and Selection Criteria: We performed three literature searches using the keywords (1) coronavirus AND comorbidities, (2) comorbidities AND immune system, and (3) lifestyle factors AND immune system. Results were screened for relevance by the main author and a total of 215 articles were thoroughly analyzed.Results: The relationship between obesity and unfavorable COVID-19 prognosis is discussed in light of the impact of chronic disease and lifestyle on the immune system. Several modifiable lifestyle factors render us susceptible to viral infections. In this context, we make a case for fostering a healthy lifestyle on a global scale.Conclusions: Obesity, additional chronic disease and an unhealthy lifestyle interactively impair immune function and increase the risk of severe infectious disease. In adverse metabolic and endocrine conditions, the immune system is geared toward inflammation. Collective effort is needed to ameliorate modifiable risk factors for obesity and chronic disease on a global scale and increase resistance to viruses like SARS-CoV-2. Show less
BackgroundThe association between obesity and lung cancer (LC) remains poorly understood. However, other indices of obesity on the basis of body shape instead of body size have not been examined... Show moreBackgroundThe association between obesity and lung cancer (LC) remains poorly understood. However, other indices of obesity on the basis of body shape instead of body size have not been examined yet. The aim of this study was to evaluate the association between different indices of body size and body shape and the risk of LC. In particular, this study examined the association between A Body Shape Index, a more precise indicator of abdominal fat than traditional anthropometric measures, and the risk of LC.MethodsIn the prospective cohort the Rotterdam Study, we analysed data of 9,689 participants. LC diagnoses were based on medical records and anthropometric measurements were assessed at baseline. Cox-regression analyses with corresponding Hazard Ratios were used to examine the association between the anthropometric measurements and the risk of LC with adjustment for potential confounders. Potential non-linear associations were explored with cubic splines using the Likelihood ratio (LR) test.ResultsDuring follow-up, 319 participants developed LC. Body mass Index (BMI) was inversely associated with the risk of lung cancer (HR 0.94, 95% CI: 0.91-0.97) and persisted after excluding lung cancer cases during the first 10 years of follow-up. There was evidence for a non-linear association between BMI and the risk of lung cancer (0,04, df = 1), which indicated that the inverse association between BMI and lung cancer was mainly present in non-obese participants. Waist circumference (WC) (HR 1.03 95% CI: 1.01-1.05), Waist-to-Hip Ratio (WHR) (HR 1.23 95% CI: 1.09-1.38) and ABSI (A Body Shape Index) (HR 1.17 95% CI: 1.05-1.30) were positively and linearly associated with the risk of lung cancer.ConclusionsBody shape rather than body size may be an important risk indicator of LC. Future research should focus on the role of visceral fat and the risk of LC as well as the underlying mechanisms. Show less
BACKGROUND: Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the associations of... Show moreBACKGROUND: Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the associations of body fat distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school--age children.METHODS AND RESULTS: In a population--based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual--energy X--ray absorptiometry, and magnetic resonance imaging to collect information on body mass index, lean mass index, fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end--diastolic volume, left ventricular mass, and mass--to--volume ratio as a marker for concentricity. All body fat measures were positively associated with right and left ventricular end--diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94-1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14- 0.57) higher left ventricular mass--to--volume ratio than normal weight children. Conditional on body mass index, higher lean mass index was associated with higher right and left ventricular end--diastolic volume and left ventricular mass, whereas higher fat mass measures were inversely associated with these cardiac measures (all P<0.05).CONCLUSIONS: Higher childhood body mass index is associated with a larger right and left ventricular size. This association is influenced by higher lean mass. In childhood, lean mass may be a stronger determinant of heart growth than fat mass. Fat mass may influence cardiac structures at older ages. Show less
Narcolepsy type 1 is a neurological sleep-wake disorder caused by the destruction of orexin (hypocretin)-producing neurons. These neurons are particularly located in the lateral hypothalamus and... Show moreNarcolepsy type 1 is a neurological sleep-wake disorder caused by the destruction of orexin (hypocretin)-producing neurons. These neurons are particularly located in the lateral hypothalamus and have widespread projections throughout the brain, where they are involved, e.g., in the regulation of the sleep-wake cycle and appetite. Interestingly, a higher prevalence of obesity has been reported in patients with narcolepsy type 1 compared to healthy controls, despite a normal to decreased food intake and comparable physical activity. This suggests the involvement of tissues implicated in total energy expenditure, including skeletal muscle, liver, white adipose tissue (WAT), and brown adipose tissue (BAT). Recent evidence from pre-clinical studies with orexin knock-out mice demonstrates a crucial role for the orexin system in the functionality of brown adipose tissue (BAT), probably through multiple pathways. Since BAT is a highly metabolically active organ that combusts fatty acids and glucose toward heat, thereby contributing to energy metabolism, this raises the question of whether BAT plays a role in the development of obesity and related metabolic diseases in narcolepsy type 1. BAT is densely innervated by the sympathetic nervous system that activates BAT, for instance, following cold exposure. The sympathetic outflow toward BAT is mainly mediated by the dorsomedial, ventromedial, arcuate, and paraventricular nuclei in the hypothalamus. This review focuses on the current knowledge on the role of the orexin system in the control of energy balance, with specific focus on BAT metabolism and adiposity in both preclinical and clinical studies. Show less
Hoekstra, M.; Sluis, R.J. van der; Hildebrand, R.B.; Lammers, B.; Zhao, Y.; Pratico, D.; ... ; Eck, M. van 2020
Objective:We tested the hypothesis that enlarged, dysfunctional HDL (high-density lipoprotein) particles contribute to the augmented atherosclerosis susceptibility associated with SR-BI (scavenger... Show moreObjective:We tested the hypothesis that enlarged, dysfunctional HDL (high-density lipoprotein) particles contribute to the augmented atherosclerosis susceptibility associated with SR-BI (scavenger receptor BI) deficiency in mice.Approach and Results:We eliminated the ability of HDL particles to fully mature by targeting PLTP (phospholipid transfer protein) functionality. Particle size of the HDL population was almost fully normalized in male and female SR-BIxPLTP double knockout mice. In contrast, the plasma unesterified cholesterol to cholesteryl ester ratio remained elevated. The PLTP deficiency-induced reduction in HDL size in SR-BI knockout mice resulted in a normalized aortic tissue oxidative stress status on Western-type diet. Atherosclerosis susceptibility was-however-only partially reversed in double knockout mice, which can likely be attributed to the fact that they developed a metabolic syndrome-like phenotype characterized by obesity, hypertriglyceridemia, and a reduced glucose tolerance. Mechanistic studies in chow diet-fed mice revealed that the diminished glucose tolerance was probably secondary to the exaggerated postprandial triglyceride response. The absence of PLTP did not affect LPL (lipoprotein lipase)-mediated triglyceride lipolysis but rather modified the ability of VLDL (very low-density lipoprotein)/chylomicron remnants to be cleared from the circulation by the liver through receptors other than SR-BI. As a result, livers of double knockout mice only cleared 26% of the fractional dose of [C-14]cholesteryl oleate after intravenous VLDL-like particle injection.Conclusions:We have shown that disruption of PLTP-mediated HDL maturation reduces SR-BI deficiency-driven atherosclerosis susceptibility in mice despite the induction of proatherogenic metabolic complications in the double knockout mice. Show less
Background: Due to a clinical and public health interest of neck circumference (NC), a better understanding of this simple anthropometric measurement, as a valid marker of body composition is... Show moreBackground: Due to a clinical and public health interest of neck circumference (NC), a better understanding of this simple anthropometric measurement, as a valid marker of body composition is necessary. Methods: A total of 119 young healthy adults participated in this study. NC was measured over the thyroid cartilage and perpendicular to the longitudinal axis of the neck. Body weight, height, waist circumference (WC), and hip circumference were measured. A Dual X-ray absorptiometry (DXA) scan was used to determine fat mass, lean mass, and visceral adipose tissue (VAT). Additionally, body mass index (BMI) and triponderal mass index (TMI), the waist to hip and waist to height ratios, and the fat mass and lean mass indexes (FMI and LMI, respectively) were calculated. Results: NC was positively associated in women (W) and men (M), with BMI (rW = 0.70 and rM = 0.84, respectively), TMI (rW = 0.63 and rM = 0.80, respectively), WC (rW = 0.75 and rM = 0.86, respectively), VAT (rW = 0.74 and rM = 0.82, respectively), Waist/hip (rW = 0.51 and rM = 0.67, respectively), Waist/height (rW = 0.68 and rM = 0.83, respectively) and FMI (rW = 0.61 and rM = 0.81, respectively). The association between NC and indicators of body composition was however weaker than that observed by BMI, TMI, WC and Waist/height in both women and men. It is of note that in women, NC was associated with FMI, VAT and LMI independently of BMI. In men, adding NC to anthropometric variables did not improve the prediction of body composition, while slight improvements were observed in women. Conclusions: Taken together, the present study provides no indication for NC as a useful proxy of body composition parameters in young adults, yet future studies should explore its usefulness as a measure to use in combination with BMI, especially in women. Show less
Background: Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously... Show moreBackground: Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined.Objective: We aimed to investigate the associations of BAT volume and F-18-fluordeoxyglucose (F-18-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans.Methods: A total of 102 young adults (65 women; age: 22.08 +/- 2.17 y; BMI: 25.05 +/- 4.93 kg/m(2)) took part in this cross-sectional study. BAT volume, BAT F-18-FDG uptake, and skeletal muscle F-18-FDG uptake were assessed by means of static F-18-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan.Results: BAT volume and F-18-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (beta: 17.612, R-2 = 0.213; P < 0.001) and the habitual energy intake (beta: 16.052, R-2 = 0.123; P = 0.001). Neither the interaction BAT volume x time elapsed after meal consumption nor that of BAT F-18-FDG uptake x time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3).Conclusions: Neither BAT volume, nor BAT F-18-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans. This trial was registered at clinicaltrials.gov as NCT02365129. Show less
Song, X.Y.; Zhang, W.H.; Hallensleben, C.; Versluis, A.; Kleij, R. van der; Jiang, Z.L.; ... ; Gobbens, R.J.J. 2020
Purpose: To investigate the prevalence of multidimensional frailty in older people with hypertension and to examine a possible relationship of general obesity and abdominal obesity to frailty in... Show morePurpose: To investigate the prevalence of multidimensional frailty in older people with hypertension and to examine a possible relationship of general obesity and abdominal obesity to frailty in older people with hypertension.Patients and Methods: A sample of 995 community-dwelling older people with hypertension, aged 65 years and older and living in Zhengzhou (China), completed the Tilburg Frailty Indicator (TFI), a validated self-report questionnaire for assessing multidimensional frailty. In addition, socio-demographic and lifestyle characteristics were assessed by self-report, and obesity was determined by measuring waist circumference and calculating the body mass index.Results: The prevalence of multidimensional frailty in this older population with hypertension was 46.5%. Using multiple linear regression analysis, body mass index was significantly associated with physical frailty (p = 0.001), and waist circumference was significantly positively associated with multidimensional frailty and all three frailty domains. Older age was positively associated with multidimensional frailty, physical frailty, and psychological frailty, while gender (woman) was positively associated with multidimensional, psychological, and social frailty. Furthermore, comorbid diseases and being without a partner were positively associated with multidimensional, physical, psychological, and social frailty. Of the lifestyle characteristics, drinking alcohol was positively associated with frailty domains.Conclusion: Multidimensional frailty was highly prevalent among Chinese community-dwelling older people with hypertension. Abdominal obesity could be a concern in physical frailty, psychological frailty, and social frailty, while general obesity was concerning in relation to physical frailty. Show less
