Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans.

Objective: Alterations in lipids in muscle and plasma have been documented in insulin-resistant people with obesity. Whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear.

Methods: Nondiabetic sedentary individuals not treated with lipid-lowering medications were studied (n = 51).

The effect of short-term overfeeding on serum lipids in healthy humans.

Objectives: While chronic obesity is associated with alterations in circulating glycerolipids, sphingolipids and plasmalogens, the effects of short-term overfeeding in humans are unclear.

Design And Methods: Healthy individuals (n = 40) were overfed by 1,250 kcal day(-1) for 28 days. Insulin sensitivity (hyperinsulinemic-euglycemic clamp), abdominal fat distribution and serum lipidomics (mass spectrometry) were assessed.

Plasma lipidomic analysis of stable and unstable coronary artery disease.

Objective: Traditional risk factors for coronary artery disease (CAD) fail to adequately distinguish patients who have atherosclerotic plaques susceptible to instability from those who have more benign forms. Using plasma lipid profiling, this study aimed to provide insight into disease pathogenesis and evaluate the potential of lipid profiles to assess risk of future plaque instability.

Methods And Results: Plasma lipid profiles containing 305 lipids were measured on 220 individuals (matched healthy controls, n=80; stable angina, n=60; unstable coronary syndrome, n=80) using electrospray-ionisation tandem mass spectrometry.

Lipidomics is providing new insight into the metabolic syndrome and its sequelae.

Purpose Of Review: The metabolic syndrome incorporating obesity, hypertension, dyslipidaemia and elevated plasma glucose has reached epidemic proportions in many Western countries leading to a dramatic increase in insulin resistance, steatosis and type 2 diabetes. Lipidomics presents a new set of tools to unravel the relationship between hyper-caloric diets and other environmental and genetic factors with the metabolic syndrome and disease progression.

Recent Findings: Plasma lipidomic studies are providing detailed characterisation of the dyslipidaemia associated with obesity and the metabolic syndrome.

Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs.

The separate impacts of the chronic diabetic state and the prevailing hyperglycemia on plasma substrates and hormones, in vivo glucose turnover, and ex vivo skeletal muscle (SkM) during exercise were examined in the same six dogs before alloxan-induced diabetes (prealloxan) and after 4-5 wk of poorly controlled hyperglycemic diabetes (HGD) in the absence and presence of approximately 300-min phlorizin-induced (glycosuria mediated) normoglycemia (NGD). For each treatment state, the approximately 15-h-fasted dog underwent a primed continuous 150-min infusion of [3-(3)H]glucose, followed by a 30-min treadmill exercise test (approximately 65% maximal oxygen capacity), with SkM biopsies taken from the thigh (vastus lateralis) before and after exercise. In the HGD and NGD states, preexercise hepatic glucose production rose by 130 and 160%, and the metabolic clearance rate of glucose (MCRg) fell by 70 and 37%, respectively, compared with the corresponding prealloxan state, but the rates of glucose uptake into peripheral tissues (Rd(tissue)) and total glycolysis (GF) were unchanged, despite an increased availability of plasma free fatty acid in the NGD state.

Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise.

The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activities and site-specific phosphorylation of acetyl-CoA carboxylase was examined in the same six dogs before alloxan (35 mg/kg)-induced diabetes (C) and after 4-5 wk of suboptimally controlled hyperglycemic and hypoinsulinemic diabetes (DHG) in the presence and absence of 300-min phlorizin (50 microg.kg-1.min-1)-induced "normoglycemia" (DNG).