White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense 1 . High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition 1 , and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D) 2 . Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

Mitochondrial dysfunction, associated with insulin resistance, is characterized by low expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) and nuclear-encoded mitochondrial genes. This deficit could be due to decreased physical activity or a decreased response of gene expression to exercise. The objective of this study was to investigate whether a bout of exercise induces the same increase in nuclear-encoded mitochondrial gene expression in insulin-sensitive and insulin-resistant subjects matched for exercise capacity. Seven lean and nine obese subjects took part. Insulin sensitivity was assessed by an 80 mU.m(-2).min(-1) euglycemic clamp. Subjects were matched for aerobic capacity and underwent a single bout of exercise at 70 and 90% of maximum heart rate with muscle biopsies at 30 and 300 min postexercise. Quantitative RT-PCR and immunoblot analyses were used to determine the effect of exercise on gene expression and protein abundance and phosphorylation. In the postexercise period, lean subjects immediately increased PGC-1alpha mRNA level (reaching an eightfold increase by 300 min postexercise) and protein abundance and AMP-dependent protein kinase phosphorylation. Activation of PGC-1alpha was followed by increase of nuclear respiratory factor-1 and cytochrome c oxidase (subunit VIc). However, in insulin-resistant subjects, there was a delayed and reduced response in PGC-1alpha mRNA and protein, and phosphorylation of AMP-dependent protein kinase was transient. None of the genes downstream of PGC-1alpha was increased after exercise in insulin resistance. Insulin-resistant subjects have a reduced response of nuclear-encoded mitochondrial genes to exercise, and this could contribute to the origin and maintenance of mitochondrial dysfunction.

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense1. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D)2. Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

Because vasodilatory dysfunction has been postulated to contribute to insulin resistance, the exercise-induced improvement in vasodilatory function may signify changes in the endothelium that could contribute to the improvement in insulin sensitivity observed after aerobic exercise training.

Peripheral edema, mild weight gain, and anemia are often observed in type II diabetic patients treated with thiazolidinediones (TZDs). Small decreases in hemoglobin (Hb) and hematocrit (Hct) appear to be a class effect of TZDs and are generally attributed to fluid retention, although experimental data are lacking. We analyzed 50 patients with type II diabetes mellitus undergoing either placebo or pioglitazone (PIO, 45 mg/day) for 16 weeks. Before and after therapy, we measured Hb/Hct and used (3)H(2)O and bioimpedance to quantitate total body water (TBW), extracellular water, and fat-free mass. The majority (89%) of the increment in body weight was accounted for by increased body fat. Hb and Hct fell significantly in the PIO group (-0.9+/-0.2 g/dl, -2.4+/-0.5%, both P<0.0001), without change in TBW. A decline in white blood cell (-0.8+/-0.1 x 10(3)/mm(3), P<0.0001) and platelet (-15+/-6 x 10(3)/mm(3), P<0.02) counts was seen after PIO. In conclusion, the small decreases in Hb/Hct observed after 16 weeks of PIO treatment cannot be explained by an increase in TBW. Other causes, such a mild marrow suppressive effect, should be explored.