Excessive secretion of triglyceride-rich very low-density lipoproteins (VLDL-TG) contributes to diabetic dyslipidemia. Earlier studies have indicated a possible role for the hypothalamus and autonomic nervous system in the regulation of VLDL-TG. In the current study, we investigated whether the autonomic nervous system and hypothalamic neuropeptide Y (NPY) release during fasting regulates hepatic VLDL-TG secretion. We report that, in fasted rats, an intact hypothalamic arcuate nucleus and hepatic sympathetic innervation are necessary to maintain VLDL-TG secretion. Furthermore, the hepatic sympathetic innervation is necessary to mediate the stimulatory effect of intracerebroventricular administration of NPY on VLDL-TG secretion. Since the intracerebroventricular administration of NPY increases VLDL-TG secretion by the liver without affecting lipolysis, its effect on lipid metabolism appears to be selective to the liver. Together, our findings indicate that the increased release of NPY during fasting stimulates the sympathetic nervous system to maintain VLDL-TG secretion at a postprandial level.
Background During the first wave of the COVID-19 pandemic older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. Objective The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. Methods This was a multi-centre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. Results A total of 1,376 patients were included (median age 78 years (IQR 74–84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6–9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 vs. 7 days), lower oxygen demand and lower levels of CRP. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared to patients with CFS 1–3, patients with CFS 4–5 had a two times higher risk (odds ratio (OR) 2.0 (95%CI 1.3–3.0) and patients with CFS 6–9 had a three times higher risk of in-hospital mortality (OR 2.8 (95%CI 1.8–4.3)). Conclusions The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.
Objective: Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monocarboxylate transporter 8 (MCT8 (SLC16A2)), MCT10, organic anion transporting polypeptide 1C1 (OATP1C1 (SLCO1C1)), and the types 2 and 3 deiodinases (D2 and D3) in the developing human hypothalamus. Design: Fifteen postmortem brain samples of fetuses and young children ranging between 17 weeks of gestation and 29 months of postnatal age including one child (28 months) with central congenital hypothyroidism were studied. Methods: Sections of the different hypothalami were stained with polyclonal rabbit antisera against MCT8, MCT10, OATP1C1, D2, and D3. Results: We found MCT8 and D3 but not D2 protein expression to be present in our earliest sample of 17 weeks of gestation, indicating triiodothyronine degradation, but not production at this time of development. At term, expression of TH transporters and D2 decreased and D3 expression increased, suggesting decreased TH signaling just before birth. The child with central congenital hypothyroidism showed higher MCT8 and D2 expression compared with the other children of similar age. Conclusions: This study reports the developmental timing of expression of components crucial for central TH signaling in the human hypothalamus. In general, during fetal hypothalamic development, the coordinated expression of D2 and D3 in combination with the different TH transporters suggests that proper TH concentrations are regulated to prevent untimely maturation of brain cells.
The arterial baroreflex regulates blood pressure by modifying heart rate and systemic vascular resistance. Baroreflex sensitivity is expressed as the relation between changes in blood pressure and the resulting changes in reciprocal values of heart rate (cardBRS) and in reciprocal values of vascular resistance (vascBRS). This study investigated determinants of vascBRS and cardBRS and their relationship in a random population sample. Continuous noninvasive arterial pressure was analyzed in 105 adults (43 males) with a median age of 45 (range 18-95) years and body mass index of 24.5 (range 18.1-39.1) kg m⁻². Systolic and diastolic blood pressures were 130 (range 95-205) and 80 (range 47-141) mmHg, and heart rate was 66 (range 42-109) beats min⁻¹. Pulse contour (CO-trek)-determined vascular resistance was 1.37 (range 0.60-7.75) mmHg s ml⁻¹. The results of vascBRS and cardBRS were log-transformed; linear regression analysis revealed that age, resistance⁻¹, systolic and diastolic blood pressures were major determinants of log(vascBRS) explaining 30.5 % of the variance. Determinants of log(cardBRS) were age, body mass index, heart rate, systolic and diastolic blood pressures, explaining 70.4 % of the variance. Thus, some established determinants of cardBRS were not correlated with vascBRS. There was no correlation between log(cardBRS) and log(vascBRS) after correction for age, supporting that vascBRS is an independent description of baroreflex regulation. These findings suggest that vascBRS and cardBRS report different modalities of cardiovascular autonomic function.
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