Objective
Serum uric acid (SUA) has been associated with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify a ...unifying mechanism linking elevated SUA to IR and VAT.
Methods
We conducted analyses in 226 subjects from the UIEM cohort with both euglycemic hyperinsulinemic clamp (EHC) and dual X‐ray absorptiometry (DXA) measurements for IR and VAT accumulation and explored the role of SUA and adiponectin by developing a network of causal mediation analyses to assess their impact on IR and VAT. These models were then translated to two population‐based cohorts comprising 6337 subjects from NHANES 2003–2004 and 2011–2012 cycles in the US and ENSANUT Medio Camino 2016 in Mexico, using HOMA2IR and adipoIR as indicators of peripheral and adipose tissue IR, and METS‐VF as a surrogate for VAT accumulation.
Results
SUA has a mediating role inside a bidirectional relationship between IR and visceral obesity, which was similar using either gold standard measurements or surrogate measures for IR and VAT. Furthermore, adiponectin acts as a linking mediator between elevated SUA and both peripheral IR and VAT accumulation. The proportion of the mechanism for IR‐mediated (in either peripheral or adipose tissue) VAT accumulation was greater, compared to VAT‐mediated IR accumulation (10.53% 9.23%–12.00% to 5.44% 3.78%–7.00%). Normal‐range SUA levels can be used to rule‐out underlying cardio‐metabolic abnormalities in both men and women.
Conclusions
Elevated SUA acts as a mediator inside the bidirectional relationship between IR and VAT accumulation and these observations could be applicable at a phenotype scale.
Fibroblast growth factor 21 (FGF21) increases glucose uptake. It is unknown if FGF21 serum levels are affected by exercise.
This was a comparative longitudinal study. Anthropometric and biochemical ...evaluation were carried out before and after a bout of exercise and repeated after two weeks of daily supervised exercise. The study sample was composed of 60 sedentary young healthy women. The mean age was 24±3.7 years old, and the mean BMI was 21.4±7.0 kg/m². The anthropometric characteristics did not change after two weeks of exercise. FGF21 levels significantly increased after two weeks of exercise (276.8 ng/l (142.8-568.6) vs. (460.8 (298.2-742.1), p<0.0001)). The delta (final-basal) log of serum FGF21, adjusted for BMI, showed a significant positive correlation with basal glucose (r = 0.23, p = 0.04), mean maximal heart rate (MHR) (r = 0.54, p<0.0001), mean METs (r = 0.40, p = 0.002), delta plasma epinephrine (r = 0.53, p<0.0001) and delta plasma FFAs (r = 0.35, p = 0.006). A stepwise linear regression model showed that glucose, MHR, METs, FFAs, and epinephrine, were factors independently associated with the increment in FGF21 after the exercise program (F = 4.32; r² = 0.64, p<0.0001).
Serum FGF21 levels significantly increased after two weeks of physical activity. This increment correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise.
ClinicalTrials.gov NCT01512368.
Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current ...treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD.
Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart ...and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes.
We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes.
EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95% CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4 C severity score, independent of obesity. EAT mediated 13.1% (95% CI 3.67-28.0%) and 5.1% (95% CI 0.19-14.0%) of the effect of age and 19.4% (95% CI 4.67-63.0%) and 12.8% (95% CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19.
EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.
Many biological pathways involved in regulating substrate metabolism display rhythmic oscillation patterns. In rodents, clock genes regulate circadian rhythms of metabolic genes and substrate ...metabolism. However, the interrelationships among substrate metabolism, metabolic genes, and clock genes have not been fully explored in people.
We tested the hypothesis that the diurnal expression pattern of pyruvate dehydrogenase kinase 4 (PDK4), a key metabolic enzyme involved in fuel switching between glucose and free fatty acids (FFAs), is associated with plasma FFA concentration and clock genes.
We analyzed peripheral blood mononuclear cells (PBMCs), subcutaneous adipose tissue, and plasma samples obtained serially during 24 hours from metabolically healthy women (n = 10) and evaluated the interrelationships among PDK4, plasma FFA, and clock genes. We also determined the potential mechanisms responsible for PDK4 transcriptional regulation by using primary human PBMCs and adipocytes.
We found that PDK4 diurnal expression patterns were similar in PBMCs and adipose tissue (ρ = 0.84, P < 0.001). The diurnal variation in PBMC PDK4 expression correlated more strongly with plasma FFA and insulin (ρ = 0.86 and 0.63, respectively, both P < 0.001) concentrations than clock genes. Data obtained from primary culture experiments demonstrated that FFAs directly induced PDK4 gene expression, at least in part through activation of peroxisome proliferator-activated receptor α.
Our results suggest that plasma FFA availability is an important regulator of diurnal expression patterns of PDK4, and we identify a novel interaction between plasma FFA and cellular diurnal rhythms in regulating substrate metabolism.
Background
The prevalence of obesity has increased worldwide in parallel with associated metabolic disturbances such as diabetes and non‐alcoholic fatty liver disease.
Objective
The objective of this ...article is to underscore discrepancies in the standard anthropometric cut‐off values and the presence of metabolic disturbances including diabetes and non‐alcoholic fatty liver disease caused by biological and ethnic variations.
Materials and methods
We performed a literature review regarding the diagnosis and prevalence of obesity, diabetes, metabolic syndrome and non‐alcoholic fatty liver disease and about the different available indicators to define obesity.
Results
There is an ongoing epidemic of these chronic diseases, partially attributed to the increased prevalence of obesity. The available markers to indicate adiposity are imperfect, and the selection of accurate cut‐off points is still not clear.
Conclusion
Methods to quantify adiposity that are useful in clinical practice should be developed to better classify individuals and to reflect metabolic risk more appropriately.
The effects of non-nutritive sweeteners (NNS) on glucose metabolism and appetite regulating hormones are not clear. There is an ongoing debate concerning NNS use and deleterious changes in ...metabolism.
The aim of this review is to analyze the scientific available evidence regarding the effects of NNS on glucose metabolism and appetite regulating hormones.
We identified human observational studies evaluating the relation between NNS consumption and obesity, diabetes, and metabolic syndrome, in addition to clinical trials evaluating the effects of NNS in glucose metabolism and appetite regulating hormones.
Fourteen observational studies evaluating the association between NNS consumption and the development of metabolic diseases and twenty-eight clinical trials studying the effects of NNS on metabolism were included. Finally, two meta-analyses evaluating the association between the consumption of NNS-containing beverages and the development of type 2 diabetes were identified.
Some observational studies suggest an association between NNS consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in observational studies. The effects of the NNS on glucose metabolism are not clear. The results of the identified clinical trials are contradictory and are not comparable because of the major existing differences between them. Studies evaluating specific NNS, with an adequate sample size, including a homogeneous study group, identifying significant comorbidities, with an appropriate control group, with an appropriate exposure time, and considering adjustment for confounder variables such as adiposity are needed.
Endoplasmic reticulum (ER) stress is likely involved in the pathogenesis of metabolic dysfunction in people with obesity and diabetes. Although tissue biopsy is often used to evaluate the presence ...and severity of ER stress, it is not known whether acute tissue injury‐induced by percutaneous muscle biopsy causes ER stress and its potential downstream effects on markers of inflammation and metabolic function. In this study, we tested the hypothesis that percutaneous biopsy‐induced tissue injury causes ER stress and alters inflammatory and metabolic pathways in skeletal muscle. Vastus lateralis muscle tissue was obtained by percutaneous biopsy at 0600 h and 12 h later from either the contralateral leg (Group 1, n = 6) or at the same site as the initial biopsy (Group 2, n = 6) in women who were overweight. Muscle gene expression of selected markers of ER stress, inflammation, and regulators of glucose and lipid metabolism were determined. Compared with Group 1, muscle gene expression in the second biopsy sample obtained in Group 2 demonstrated marked increases in markers of ER stress (GRP78, XBP1, ATF6) and inflammation (IL6, TNF), and alterations in metabolic regulators (decreased expression of GLUT4 and PPARGC1A and increased expression of FASN). Our results suggest that acute tissue injury induced by percutaneous muscle biopsy causes an integrated local response that involves an induction of ER stress and alterations in markers of inflammation and regulators of glucose and lipid metabolism.
This study shows acute tissue injury induced by percutaneous muscle biopsy causes local endoplasmic reticulum (ER) stress in conjunction with transcriptional changes in markers of inflammation and metabolic function. These results suggest ER stress, inflammation, and alterations in cellular metabolic function are components of an integrated acute response to help repair muscle injury induced by percutaneous biopsy.
Arterial stiffness may be associated with glucose metabolism parameters, such as HbA1c, mainly via insulin resistance. We aimed to investigate the association between arterial stiffness and HbA1c and ...explore the mediator effect of insulin resistance. In this cross-sectional study, arterial stiffness (pulse-wave velocity; PWV), HbA1c, and insulin resistance (METS-IR) were determined in Hispanic adults. In addition to sex and age, various biochemical measurements (glucose, lipid profile, etc.) and adipose tissue (fat mass and visceral fat mass) were considered as potential confounding variables. A multivariate regression analysis shows that HbA1c is associated with PWV, even after adjusting for several confounding variables. Importantly, the results show that insulin resistance mediated 17.9% of the effect of HbA1c over PWV. In conclusion, HbA1c may be a potential resource for predicting arterial stiffness due to the influence of insulin resistance in Hispanic subjects.
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