Obesity-related respiratory failure is increasingly common but remains under-diagnosed and under-treated. There are several clinical phenotypes reported, including severe obstructive sleep apnoea (OSA), isolated nocturnal hypoventilation with or without severe OSA and OSA complicating chronic obstructive pulmonary disease (COPD). The presence of hypercapnic respiratory failure is associated with poor clinical outcomes in each of these groups. While weight loss is a core aim of management, this is often unachievable, and treatment of sleep-disordered breathing with positive airway pressure (PAP) therapy is the mainstay of clinical practice. Although there are few long-term clinical efficacy trials, the lack of equipoise would prevent the utilization of an untreated control group. The current data support the use of PAP therapy to improve respiratory failure and is associated with improvements in health-related quality of life, reduced healthcare utilization and reduced mortality. Both continuous PAP (CPAP) and non-invasive ventilation (NIV) appear safe and effective in patients with obesity-related respiratory failure and OSA, with or without COPD, and the current evidence would not support a single therapy choice in all patients. There are no studies of CPAP in patients with isolated nocturnal hypoventilation, and NIV would be the current recommendation in this patient group. Whichever starting therapy is used, titration should be performed to correct sleep-disordered breathing and reverse chronic respiratory failure, with consideration of step-down of the treatment based on a clinical re-evaluation. In contrast, failure to reach physiological and clinical treatment targets should lead to the consideration of treatment escalation.

We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted using random-effects models with Hedges' g as the effect size estimate. We identified 31 eligible studies, investigating the levels of 7 appetite regulating hormones (adiponectin, insulin, leptin, ghrelin, orexin, resistin and visfatin) in 1792 FEP patients and 1364 controls. The insulin levels in FEP patients were higher than in controls (g = 0.34, 95%CI: 0.19 - 0.49, p < 0.001), even considering only antipsychotic-naïve patients (g = 0.39, 95%CI: 0.12 - 0.66, p = 0.005). The severity of negative symptoms was positively associated with the effect size estimates (β = 0.08, 95%CI: 0.01 - 0.16, p = 0.030). Moreover, we found lower levels of leptin in antipsychotic-naïve FEP patients (g = -0.62, 95%CI: -1.11 - 0.12, p = 0.015). Impaired appetite regulation, in terms of elevated insulin levels and decreased leptin levels, occurs in early psychosis, before antipsychotic treatment. Hyperinsulinemia might be related to negative symptoms.

Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derived factor (PEDF), a protein isolated from retinal pigment epithelial cells, has multiple functions, including neuronal protection, antineoplastic effects, and anti-inflammatory activity. The aim of this study is to investigate the antiobesity effects of PEDF. The antiobesity effects of PEDF on fat accumulation, inflammation, energy expenditure, insulin resistance, and obesity-related physiological parameters and protein levels were assessed in high-fat diet (HFD)-induced obese mice in vivo and in 3T3-L1 adipocytes, palmitate (PA)-treated HepG2 cells, and C2C12 myotubes in vitro. In an in vivo assay, PEDF effectively decreased body weight gain, white adipose tissue mass, and inflammation and improved insulin resistance, dyslipidemia, and hyperglycemia in HFD-induced mice. In liver tissue, PEDF decreased lipid accumulation and fibrosis. In an in vitro assay, PEDF diminished the differentiation of 3T3-L1 preadipocytes. We also determined that PEDF promoted lipolysis and prolonged cell cycle progression, through the mTOR-S6K pathway and downstream transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α (CEBP-α), and CEBP-β. In addition, PEDF decreased reactive oxygen species production in PA-induced HepG2 cells and improved glucose uptake ability in PA-induced HepG2 cells and C2C12 myotubes. In the present study, PEDF protected against HFD-induced obesity and metabolic disorders in mice, inhibited adipogenesis, and improved insulin resistance. These results provide a new potential treatment for obesity in the future.

This study investigated the impact of exercise training on interindividual variability and response rates in body composition and cardiometabolic outcomes in adolescents with obesity. Postpubertal males and females (n=143) were randomly assigned to six-months of a diet-only Control or Aerobic, Resistance, or Combined exercise training. Body composition indices were percentages of body fat mass (%BFM) and lean body mass (%LBM), and waist circumference (WC). Biomarkers of cardiometabolic health were systolic blood pressure (SBP) and plasma fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Interindividual variability was examined by comparing the standard deviation of individual responses (SDIR) to a smallest robust change (SRC). The typical error of measurement was used to classify responses. SDIR exceeded the SRC for %BFM in all exercise groups (SRC=1.04%; Aerobic SDIR=1.50%; Resistance SDIR=1.22%; Combined SDIR=2.29%), %LBM (SRC=1.38%; SDIR=3.2%,) and SBP (SRC=2.06 mmHg; SDIR=4.92 mmHg) in the Resistance group, and WC (SRC=2.33 cm; SDIR=4.09 cm) and fasting glucose (SRC=0.08 mmol/L; SDIR=0.28 mmol/L) in the Combined group. However, half of the reported variables (11/21) did not have a positive SDIR. Importantly, adverse response rates were significantly lower in all three exercise groups than control for body composition. Although exercise had a small influence on interindividual variability for indices of body composition, the rate of adverse responses did not increase for any outcome. -Interindividual variability and individual responses to exercise training have not been investigated in adolescents with obesity. -Six-months of exercise training does not increase interindividual variability in adolescents with obesity. -Exercise created a positive, uniform shift in responses.

Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18β-Glycyrrhetinic acid (18β-GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18β-GA on sRAGE secretion via TRPC channels in high glucose (HG)-induced THP-1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide-adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18β-GA showed the dramatic effects similar to Pyr3 or 2-aminoethyl diphenyl borinate inhibitors and effectively reversed HG-elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18β-GA provides a potential implication to diabetes mellitus and its complications.

Effective strategies to improve health education, food choices, and physical activity are vital for people with intellectual and developmental disabilities (IDD), as their sedentary lifestyles and high fat diets are contributing to poor health, such as cardiovascular disease, osteoporosis, hypertension, Type II diabetes, and obesity. This study examined the effectiveness of a peer-led health promotion program for people with IDD. One group pre/post-test design was used to test the feasibility and effectiveness of the 12-week HealthMessages Program for three groups: peer health coaches (PHCs), mentors, and peer participants. A total of 379 volunteers participated including PHCs people with IDD (n = 33), mentors-staff from community organizations (n = 35), and peer participants-peers with IDD (n = 311). Following the intervention and 12-week HealthMessages Program, PHCs had significant changes in physical activity and hydration knowledge, mentors had significant changes in self-efficacy scores, and peer participants had significant changes in physical activity and hydration knowledge, social supports, and total health behaviors. A dyad approach supported PHCs and mentors to implement a successful HealthMessages Program with their peers.