AIMS: The metabolic syndrome (MetS) is a risk factor for cancer. However, it is not known if the MetS confers a greater cancer risk than the sum of its individual components, which components drive the association, or if the MetS predicts future cancer risk. MATERIALS AND METHODS: We linked 20,648 participants from the Australian and New Zealand Diabetes and Cancer Collaboration with complet...

Activin A, a member of the transforming growth factor-β superfamily, is stimulated early in inflammation via the Toll-like receptor (TLR) 4 signalling pathway, which is also activated in myocardial ischaemia-reperfusion. Neutralising activin A by treatment with the activin-binding protein, follistatin, reduces inflammation and mortality in several disease models. This study assesses the regulat...

Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/delet...

Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and has anti-obesity effects; however, it is not known which inflammasome regulates this process. We found that mice lacking the NLRP1 inflammasome phenocopy mice lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein ...

Liver steatosis is associated with the development of insulin resistance and the pathogenesis of type 2 diabetes. We tested the hypothesis that protein signals originating from steatotic hepatocytes communicate with other cells to modulate metabolic phenotypes. We show that the secreted factors from steatotic hepatocytes induce pro-inflammatory signaling and insulin resistance in cultured cells...

Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would...

Interleukin-6 (IL-6) plays a paradoxical role in inflammation and metabolism. The pro-inflammatory effects of IL-6 are mediated via IL-6 "trans-signaling," a process where the soluble form of the IL-6 receptor (sIL-6R) binds IL-6 and activates signaling in inflammatory cells that express the gp130 but not the IL-6 receptor. Here we show that trans-signaling recruits macrophages into adipose tis...

Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transpl...

ABCA12 is involved in the transport of ceramides in skin, but it may play a wider role in lipid metabolism. We show that, in Abca12-deficient macrophages, cholesterol efflux failed to respond to activation with LXR agonists. Abca12 deficiency caused a reduction in the abundance of Abca1, Abcg1, and Lxrβ. Overexpression of Lxrβ reversed the effects. Mechanistically, Abca12 deficiency did not aff...

Oxidative stress is an important contributor to glial and vascular cell damage in ischemic retinopathies. We hypothesized that ebselen via its ability to reduce reactive oxygen species (ROS) and augment nuclear factor-like 2 (Nrf2) anti-oxidants would attenuate hypoxia-induced damage to macroglial Müller cells and also lessen retinal vasculopathy. Primary cultures of rat Müller cells were expos...

Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Ma...

BACKGROUND: Patients following laparoscopic adjustable gastric banding (LAGB) are generally advised to avoid liquid calories, opt for solids and refrain from drinking with meals as this is believed to prolong satiety. The role of food consistency and satiety following LAGB is largely uninvestigated. The purpose of the study was to: (1) determine if food consistency impacts on post meal satie...

BACKGROUND: Physical inactivity and sedentary behaviour are common amongst breast cancer survivors. These behaviours are associated with an increased risk of comorbidities such as heart disease, diabetes and other cancers. Commercially available, wearable activity trackers (WATs) have potential utility as behavioural interventions to increase physical activity and reduce sedentary behaviour ...

Children spend over 60% of their school day sitting; much of this occurs in the classroom. Emerging research has examined the impact of environmental interventions on classroom sitting. While this research is promising, it has predominantly focused on the primary school setting. This study examined the impact and feasibility of height-adjustable desks on time spent sitting/standing during class...

During school hours, children can sit for prolonged and unbroken periods of time. This study investigated the impact of an 8-month classroom-based intervention focusing on reducing and breaking-up sitting time on children's cardio-metabolic risk factors (i.e., body mass index, waist circumference, blood pressure) and perceptions of musculoskeletal discomfort. Two Year-6 classes (24 students per...

Background and Purpose: Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categ...

OBJECTIVE: With improvements in cardiovascular disease (CVD) rates among people with diabetes, mortality rates may also be changing. However, these trends may be influenced by coding practices of CVD-related deaths on death certificates. We analyzed trends of mortality over 13 years in people with diabetes and quantified the potential misclassification of CVD mortality according to current cod...

L-sulforaphane (LSF) is a natural isothiocyanate found in cruciferous vegetables particularly broccoli. LSF has been identified as a potent antioxidant and anti-cancer agent and is widely known to regulate phase II detoxifying enzymes and induce cell cycle arrest or apoptosis in malignant cells in vitro and in vivo. Previous studies have found significant G2/M cell cycle arrest in response to L...

The activity of phospholipase Cβ1b (PLCβ1b) is selectively elevated in failing myocardium and cardiac expression of PLCβ1b causes contractile dysfunction. PLCβ1b can be selectively inhibited by expressing a peptide inhibitor that prevents sarcolemmal localization. The inhibitory peptide, PLCβ1b-CT was expressed in heart from a mini-gene using adeno-associated virus (rAAV6-PLCβ1b-CT). rAAV6-PLCβ...

OBJECTIVE: The present study assessed the impact of the retailer-led removal of unhealthy beverages from display at a self-service café within a major health service. While unhealthy beverages remained available from behind the counter upon request, this was not communicated directly to customers. DESIGN: Drinks were categorised based on the state government nutrient profiling system, cl...