Visceral adipose tissue (VAT) imaged by computed tomography (CT) or magnetic resonance imaging (MRI) is associated with the metabolic syndrome features, being morphologically and functionally different from subcutaneous adipose tissue (SAT). Insulin effect is lower and catecholamine effect higher in visceral adipose tissue, with its metabolites and its secretions draining through portal system, partially at least, to the liver. Thus, visceral cells transfer and release fatty acids more extensively, have increased glucocorticoid and reduced thiazolidinedione responses, produce more angiotensinogen, interleukin-6 and plasminogen activator inhibitor-1, and secrete less leptin and adiponectin than SAT. Furthermore, there are regional differences in the intrinsic characteristics of the preadipocytes, with those of SAT presenting greater differentiation and fat cell gene expression but less apoptosis than that of VAT. All features contribute to the morbidity associated with increased VAT. To evaluate the relationship between VAT and components of the metabolic syndrome, 55 non-diabetic women, 11 lean (VAT < 68 cm 2) and 44 obese were studied. The obese with VAT within the normal range (VAT < or = 68 cm 2) had higher BMI, WHR, BP and resistance to FFA suppression during oGTT in comparison to the lean controls. The obese with VAT > 68 cm 2 compared to those with VAT < or = 68 cm 2 had similar body mass index (BMI) but significantly higher in vivo homeostasis model assessment for insulin resistance (HOMA IR ) results and triglycerides. By pooling all data, correlation analysis indicated that VAT contributes more to insulin resistance (HOMA IR ) than SAT does, but not when insulin-suppressed plasma free fatty acids during oral glucose tolerance test as an index of insulin resistance are taken into consideration.

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription–PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

Local production of growth factors may play a major role in vascular repair after injury. We examined the regulation of insulin-like growth factor-I (IGF-I) and its specific membrane receptor in balloon-denuded rat aorta. Aortic IGF-I mRNA and radioimmunoassayable IGF-I content increased severalfold after balloon denudation with a peak at 7 d after injury. This coincided with a reciprocal 25% decrease in IGF-I receptor mRNA content and a 40% decrease in total '25I-IGF-I binding.Scatchard analysis indicated a single class of binding sites, with a decrease in receptor number at 7 d compared to control and no change in affinity. By in situ hybridization the predominant site of IGF-I expression in the normal and the denuded vessel wall was the medial smooth muscle cell. After denudation there was a relative decrease in IGF-I receptor mRNA in the medial cells as compared to the neointima, suggesting that the site of IGF-I action was predominantly in the medial layer. These data suggest that local expression and action of IGF-I are significant in the promotion of smooth muscle cell proliferation after arterial injury. (J. Clin. Invest. 1992. 90:1926-1931