The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and ␤-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor ␣. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo.In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.

OBJECTIVE -The high-molecular weight (HMW) form of adiponectin, an adipocytederived insulin-sensitizing hormone, has been reported to be the most active form of this hormone. We investigated whether measurement of plasma HMW adiponectin levels, using our newly developed enzyme-linked immunosorbent assay system for selective measurement of human HMW adiponectin level, may be useful for the prediction of insulin resistance and metabolic syndrome.RESEARCH DESIGN AND METHODS -A total of 298 patients admitted for diabetes treatment or coronary angiography served as study subjects. Receiver operator characteristic (ROC) curves for the HMW ratio (HMWR; ratio of plasma level of HMW adiponectin to that of total adiponectin) and plasma total adiponectin levels were plotted to predict the presence of insulin resistance and metabolic syndrome. CONCLUSIONS -The HMWR value has better predictive power for the prediction of insulin resistance and metabolic syndrome than plasma total adiponectin level. RESULTS Diabetes Care 29:1357-1362, 2006A diponectin (also known as ACRP30, GBP28, and AdipoQ) is a hormone secreted exclusively by adipocytes (1-4). Adiponectin replenishment has been found to ameliorate the abnormalities of metabolic syndrome, including insulin resistance, hyperglycemia, and dyslipidemia, in a murine model of obesity-linked metabolic syndrome associated with decreased adiponectin levels (5). Adiponectin-deficient mice (6,7) have been demonstrated to show features of metabolic syndrome, such as insulin resistance, glucose intolerance, dyslipidemia, and hypertension. In humans, decreased plasma adiponectin levels have been demonstrated in patients with obesity, diabetes, and coronary artery disease (8 -10), all of which are linked to insulin resistance. Moreover, the degree of hypoadiponectinemia has been reported to be correlated with the degree of insulin resistance (11,12), and hypoadiponectinemia has been shown to be closely associated with the clinical phenotype of metabolic syndrome (13,14). The gene encoding adiponectin (APM1) has been mapped to chromosome 3q27, which has been reported to be linked to type 2 diabetes and metabolic syndrome by genome-wide scans in Japanese (15), American, (16), and French-Caucasian (17) populations. A single nucleotide polymorphism in the adiponectin gene was shown to be associated with hypoadiponectinemia, insulin resistance, and increased risk of type 2 diabetes (18,19), indicating that adiponectin may play a crucial role in the regulation of insulin sensitivity and glucose and lipid metabolism and that reduced plasma adiponectin levels caused by genetic and environmental factors may lead to the development of insulin resistance, type 2 diabetes, and metabolic syndrome (20). Indeed, a recent study demonstrated that individuals with high plasma adiponectin levels had a substantially lower relative risk of developing type 2 diabetes, even after adjustment for conventional risk factors, such as BMI (21,22).We have reported that adiponectin forms multimers and is present in th...

We recently isolated a Krüppel-like zinc-finger transcription factor 5 (KLF5; also known as BTEB2 and IKLF), which is markedly induced in activated vascular smooth-muscle cells and fibroblasts. Here we describe our analysis of the in vivo function of KLF5 using heterozygous KLF5-knockout mice (Klf5(+/-)). In response to external stress, Klf5(+/-) mice showed diminished levels of arterial-wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis. Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression. In addition, we determined that KLF5 interacted with the retinoic-acid receptor (RAR), that synthetic RAR ligands modulated KLF5 transcriptional activity, and that in vivo administration of RAR ligands affected stress responses in the cardiovascular system in a KLF5-dependent manner. KLF5 thus seems to be a key element linking external stress and cardiovascular remodeling.

Nonpolypoid colorectal neoplasms are grossly classified into three groups: slightly elevated (small flat adenomas), laterally spreading, and depressed. Flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when they are extremely small. Nonpolypoid lesions are difficult to detect and are often overlooked. Keys to detect them are their slight color change, interruption of the capillary network pattern, slight deformation of the colonic wall, spontaneously bleeding spots, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves. Spraying of indigo carmine dye helps to clarify the lesions. A pit pattern analysis with a zoom colonoscope is useful for the diagnosis and staging of early colorectal cancer. Small flat adenomas are thought to be precursors of protruded polyps and lateral spreading tumors, whereas depressed lesions are thought to grow endophytically and become advanced cancers. Small depressed lesions are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Laterally spreading tumors are not as invasive despite their large size and therefore are good indications for the EMR or piecemeal EMR method. Small flat adenomas need not be treated urgently, as almost none is invasive. Accurate diagnosis with dye-spraying and zoom colonoscopy is vital for deciding the treatment strategy.

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