Systolic Blood Pressure is Related to Catecholamine Sensitivity in Subcutaneous Abdominal Fat Cells

A relationship between abdominal obesity and hypertension is well established. In search for an early-onset defect in adipocyte function linking these two conditions, we compared catecholamine sensitivity in subcutaneous abdominal fat cells with 24-hour systolic, mean arterial and diastolic blood pressure in 16 healthy, normotensive subjects. Clear inter-individual variations in the adipocyte lipolytic adrenoceptor sensitivity (pD₂) for noradrenaline were observed in dose-response experiments (i.e., about 4 log units). An inverse and independent correlation was found between the 24-hour systolic blood pressure and pD₂ for noradrenaline (r = ?0.67, p < 0.01). The mean arterial blood pressure was also negatively correlated to peripheral noradrenaline sensitivity (r = ?0.58, p < 0.05). However, no significant relationship between the 24-hour diastolic blood pressure and pD₂ for noradrenaline was demonstrated. In conclusion we suggest that catecholamine resistance in subcutaneous fat cells may be associated with autonomic dysfunction and impaired blood pressure regulation. This finding is supported by the fact that both noradrenaline sensitivity and 24-hour systolic blood pressure also are correlated to the individual orthostatic heart rate responses, reflecting the sympathetic nervous system tone (r=0.61, p=0.01 and r= ?0.53, p=0.03, respectively). The relationship between noradrenaline sensitivity and systolic blood pressure may be of importance in the early development of hypertension in man.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin.

The effects of acylation-stimulating protein (ASP) and insulin on free fatty acid (FFA) release from isolated human fat cells and the signal transduction pathways to induce these effects were studied. ASP and insulin inhibited basal and norepinephrine-induced FFA release by stimulating fractional FFA re-esterification (both to the same extent) and by inhibiting FFA produced during lipolysis (ASP to a lesser extent than insulin). Protein kinase C inhibition influenced none of the effects of ASP or insulin. Phosphatidylinositol 3-kinase inhibition counteracted the effects of insulin but not of ASP. Phosphodiesterase 3 (PDE3) activity was stimulated by ASP and insulin, whereas PDE4 activity was slightly increased by ASP only. Selective PDE3 inhibition reversed the effects of both ASP and insulin on fractional FFA re-esterification and lipolysis. Selective PDE4 inhibition slightly counteracted the ASP but not the effect of insulin on fractional FFA re-esterification and did not prevent the action of ASP or insulin on lipolysis. Thus, ASP and insulin play a major role in regulating FFA release from fat cells as follows: insulin by stimulating fractional FFA re-esterification and inhibiting lipolysis and ASP mainly by stimulating fractional FFA re-esterification. For both ASP and insulin these effects on FFA release are mediated by PDE3, and for ASP PDE4 might also be involved. The signaling pathway preceding PDE is not known for ASP but involves phosphatidylinositol 3-kinase for insulin.     

Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin<Superscript>21-157</Superscript>

Introduction  

Chemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators.     

Differentiation at the MHCIIα and Cath2 Loci in Sympatric Salvelinus alpinus Resource Morphs in Lake Thingvallavatn

Northern freshwater fish may be suitable for the genetic dissection of ecological traits because they invaded new habitats after the last ice age (∼10.000 years ago). Arctic charr (Salvelinus alpinus) colonizing streams and lakes in Iceland gave rise to multiple populations of small benthic morphotypes, often in sympatry with a pelagic morphotype. Earlier studies have revealed significant, but subtle, genetic differentiation between the three most common morphs in Lake Thingvallavatn. We conducted a population genetic screen on four immunological candidate genes Cathelicidin 2 (Cath2), Hepcidin (Hamp), Liver expressed antimicrobial peptide 2a (Leap-2a), and Major Histocompatibility Complex IIα (MHCIIα) and a mitochondrial marker (D-loop) among the three most common Lake Thingvallavatn charr morphs. Significant differences in allele frequencies were found between morphs at the Cath2 and MHCIIα loci. No such signal was detected in the D-loop nor in the other two immunological genes. In Cath2 the small benthic morph deviated from the other two (F_ST = 0.13), one of the substitutions detected constituting an amino acid replacement polymorphism in the antimicrobial peptide. A more striking difference was found in the MHCIIα. Two haplotypes were very common in the lake, and their frequency differed greatly between the morphotypes (from 22% to 93.5%, F_ST = 0.67). We then expanded our study by surveying the variation in Cath2 and MHCIIα in 9 Arctic charr populations from around Iceland. The populations varied greatly in terms of allele frequencies at Cath2, but the variation did not correlate with morphotype. At the MHCIIα locus, the variation was nearly identical to the variation in the two benthic morphs of Lake Thingvallavatn. The results are consistent with a scenario where parts of the immune systems have diverged substantially among Arctic charr populations in Iceland, after colonizing the island ∼10.000 years ago.     

Who is the Treatment-Seeking Young Adult with Severe Obesity: A Comprehensive Characterization with Emphasis on Mental Health

Objective

To characterize treatment-seeking young adults (16–25 years) with severe obesity, particularly mental health problems.

Study Design and Participants

Cross-sectional study of 165 participants (132 women, 33 men) with BMI ≥35 kg/m² or ≥30 kg/m² with comorbidities, enrolling in a multidisciplinary obesity treatment program.

Method

Data collection at admission of present and life-time health issues including symptomatology of anxiety, depression (Hospital Anxiety and Depression Scale) and attention-deficit/hyperactivity disorder (Adult ADHD Self-Report scale); self-esteem (Rosenberg Self-Esteem Scale), suicide attempts, health-related quality of life (Short Form-36 Health Survey), psychosocial functioning related to obesity (Obesity-related Problems Scale), cardiorespiratory fitness (Astrand´s bicycle ergometer test), somatic and psychiatric co-morbidities, cardiometabolic risk factors, and micronutritional status. We used multiple regression analysis to identify variables independently associated with present anxiety and depressive symptomatology.

Results

Mean body mass index was 39.2 kg/m² (SD = 5.2). We found evidence of poor mental health, including present psychiatric diagnoses (29%), symptomatology of anxiety (47%), depression (27%) and attention-deficit/hyperactivity disorder (37%); low self-esteem (42%), attempted suicide (12%), and low quality of life (physical component score = 46, SD = 11.2; mental component score = 36, SD = 13.9, P<0.001 for difference). Variables independently associated with present anxiety symptomatology (R ² = 0.33, P<0.001) included low self-esteem (P<0.001) and pain (P = 0.003), whereas present depressive symptomatology (R ² = 0.38, P<0.001) was independently associated with low self-esteem (P<0.001), low cardiorespiratory fitness (P = 0.009) and obesity-related problems (P = 0.018). The prevalence of type 2 diabetes was 3%, and hypertension 2%. Insulin resistance was present in 82%, lipid abnormality in 62%, and poor cardiorespiratory fitness in 92%. Forty-eight percent had at least one micronutritional deficiency, vitamin D being the most common (35%).

Conclusion

A wide range of health issues, including quite severe mental health problems, was prevalent in treatment-seeking young adults with severe obesity. These are likely to constitute a major treatment challenge, including options relating to bariatric surgery.