Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet-induced obesity and type 2 diabetes we aimed at investigating the impact of Apoa1 or Lcat deficiency, two key proteins of peripheral HDL metabolic pathway, on these pathological conditions in mouse models. We report that universal deletion of apoa1 or lcat expression in mice fed western-type diet results in increased sensitivity to body-weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discrete effects on white adipose tissue (WAT) metabolic activation and plasma glucose homeostasis. Apoa1-deficiency results in reduced WAT mitochondrial non-shivering thermogenesis. Lcat-deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non-shivering thermogenesis, rendering lcat^?/? mice the most sensitive to weight gain out of the three strains tested, followed by apoa1^?/? mice. Nevertheless, only apoa1^?/? mice show disturbed plasma glucose homeostasis due to dysfunctional glucose-stimulated insulin secretion in pancreatic β-islets and insulin resistant skeletal muscles. Our analyses show that both apoa1^?/? and lcat^?/? mice fed high-fat diet have no measurable Apoa1 levels in their plasma, suggesting no direct involvement of Apoa1 in the observed phenotypic differences among groups.     

High Thyrotropin Levels and Risk of Mortality in the Elderly With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis

ObjectiveThis study aims to determine whether elevated endogenous thyrotropin levels contribute to an increased risk of adverse outcomes, such as all-cause mortality in older adults with subclinical hypothyroidism.MethodsEight electronic databases were searched for relevant articles from inception until March 23, 2022. Cohort studies assessing the association between thyrotropin levels and the risk of mortality among older adults aged ≥60 years with subclinical hypothyroidism were eligible. The outcomes of interest were either all-cause or cardiovascular-related mortality. Two independent researchers assessed the eligibility of the studies and collected data through a previously defined data extraction form. The Newcastle-Ottawa Scale was used to evaluate the quality of evidence, and multivariate-adjusted hazard ratios (HRs) (95% Cl) were collected as the necessary risk estimate for synthesis. Random-effects models were applied for meta-analysis.ResultsOverall, 13 studies involving 44 514 participants were included in this meta-analysis. There were no significant differences in the risk of all-cause mortality (pooled HR: 1.18 [95% Cl: 0.95, 1.45], I² = 94%) and cardiovascular-related mortality (pooled HR: 1.08 [95% Cl: 0.94, 1.23], I² = 0%) between euthyroid older adults and older adults with subclinical hypothyroidism. The results remained the same when only older adults with thyrotropin ≥10 mIU/L were assessed (pooled HR for all-cause mortality and cardiovascular-related mortality, respectively: 1.53 [95% Cl: 0.81, 2.88], I² = 22%, 1.35 [95% Cl: 0.63, 2.86], I² = 43%).ConclusionHigh thyrotropin levels are not associated with increased risk for all-cause mortality as well as cardiovascular-related mortality in older adults aged ≥60 years with subclinical hypothyroidism, suggesting an unnecessity in initialing treatment.