Adiposity influences on myocardial deformation: a cardiovascular magnetic resonance feature tracking study in people with overweight to obesity without established cardiovascular disease.

The objective of this study was to assess whether dietary-induced weight loss improves myocardial deformation in people with overweight to obesity without established cardiovascular disease applying cardiovascular magnetic resonance (CMR) with feature tracking (FT) based strain analysis. Ninety people with overweight to obesity without established cardiovascular disease (age 44.6 ± 9.3 years, body mass index (BMI) 32.6 ± 4 kg/m2) underwent CMR. We retrospectively quantified FT based strain and LA size and function at baseline and after a 6-month hypocaloric diet, with either low-carbohydrate or low-fat intake. The study cohort was compared to thirty-four healthy normal-weight controls (age 40.8 ± 16.0 years, BMI 22.5 ± 1.4 kg/m2). At baseline, the study cohort with overweight to obesity without established cardiovascular disease displayed significantly increased global circumferential strain (GCS), global radial strain (GRS) and LA size (all p < 0.0001 versus controls) but normal global longitudinal strain (GLS) and normal LA ejection fraction (all p > 0.05 versus controls). Dietary-induced weight loss led to a significant reduction in GCS, GRS and LA size irrespective of macronutrient composition (all p < 0.01). In a population with overweight to obesity without established cardiovascular disease subclinical myocardial changes can be detected applying CMR. After dietary-induced weight loss improvement of myocardial deformation could be shown. A potential clinical impact needs further studies.

Role of human Kallistatin in glucose and energy homeostasis in mice.

OBJECTIVE: Kallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown. METHODS: Kallistatin mRNA expression in human subcutaneous white adipose tissue (sWAT) of 47 people with overweight to obesity of the clinical trial "Comparison of Low Fat and Low Carbohydrate Diets With Respect to Weight Loss and Metabolic Effects (B-SMART)" was measured. Moreover, we studied transgenic mice systemically overexpressing human KST (hKST-TG) and wild type littermate control mice (WT) under normal chow (NCD) and high-fat diet (HFD) conditions. RESULTS: In sWAT of people with overweight to obesity, KST mRNA increased after diet-induced weight loss. On NCD, we did not observe differences between hKST-TG and WT mice. Under HFD conditions, body weight, body fat and liver fat content did not differ between genotypes. Yet, during intraperitoneal glucose tolerance tests (ipGTT) insulin excursions and HOMA-IR were lower in hKST-TG (4.42 ± 0.87 AU, WT vs. 2.20 ± 0.27 AU, hKST-TG, p < 0.05). Hyperinsulinemic euglycemic clamp studies with tracer-labeled glucose infusion confirmed improved insulin sensitivity by higher glucose infusion rates in hKST-TG mice (31.5 ± 1.78 mg/kg/min, hKST-TG vs. 18.1 ± 1.67 mg/kg/min, WT, p < 0.05). Improved insulin sensitivity was driven by reduced hepatic insulin resistance (clamp hepatic glucose output: 7.7 ± 1.9 mg/kg/min, hKST-TG vs 12.2 ± 0.8 mg/kg/min, WT, p < 0.05), providing evidence for direct insulin sensitizing effects of KST for the first time. Insulin sensitivity was differentially affected in skeletal muscle and adipose tissue. Mechanistically, we observed reduced Wnt signaling in the liver but not in skeletal muscle, which may explain the effect. CONCLUSIONS: KST expression increases after weight loss in sWAT from people with obesity. Furthermore, human KST ameliorates diet-induced hepatic insulin resistance in mice, while differentially affecting skeletal muscle and adipose tissue insulin sensitivity. Thus, KST may be an interesting, yet challenging, therapeutic target for patients with obesity and insulin resistance.

Effects of a randomized-controlled and online-supported physical activity intervention on exercise capacity, fatigue and health related quality of life in patients with post-COVID-19 syndrome.

BACKGROUND: The Post-COVID-19 syndrome (PCS), which can occur after acute respiratory syndrome coronavirus 2 infection, leads to restrictions in everyday activity. Our study assessed the impact of an online-guided intervention which intended to facilitate physical activity on the mental and physical capability of PCS patients. METHODS: We randomized 62 patients with PCS (20 male/ 42 female; age: 46 ± 12 years; body mass index: 28.7 ± 6.7 kg/m2) with a score ≥ 22 in the fatigue assessment scale (FAS) to a 3-month exercise-focused intervention (IG n = 30) or control period (CG n = 32). We assessed changes in exercise capacity (bicycle exercise test with measurements of gas exchange), fatigue, markers of health-related quality of life (HrQoL) and mental health. RESULTS: The FAS score decreased significantly in both study groups (IG: 35.1 ± 7.4 to 31.8 ± 8.5 points; CG: 35.6 ± 7.4 to 32.6 ± 7.5 points, both p < 0.01). Exercise capacity did not increase in the CG or IG (within-group changes for IG: peak oxygen uptake: 0.9 ± 2.6 ml/min/kg, p = 0.098; peak power output: 6.1 ± 17.8 W, p = 0.076) with no significant changes in HrQoL and work ability. Patients with a FAS score at baseline ≥ 35 (severe fatigue) showed no change in exercise capacity with the 3-month intervention whereas the sub-group of patients with FAS < 35 points (moderate fatigue) showed improvements, independent of the study group. CONCLUSIONS: Our 3-month intervention seems appropriate for patients with moderate fatigue, whereas those with more severe fatigue appear to be too restricted with respect to their mental or physical health status to perform exercise at a level which is sufficient to improve markers of physical performance. TRIAL REGISTRATION: German Clinical Trials Register (registration trial number: DRKS00026245) on September 2 2021.