The University of Osaka · Medicine
Professor Hitoshi Nishizawa's research lab focuses on metabolic regulation, particularly the endocrine and secretory functions of adipose tissue, liver, and skeletal muscle in the context of metabolic diseases such as obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). The lab investigates adipokines and novel secretory factors—like musclin and adiponectin—along with key metabolic regulators such as SHP and IGF-I, to understand their roles in insulin sensitivity, fibrosis, and lipid/glucose homeostasis. A central theme is the crosstalk between endocrine organs and systemic metabolism, with translational aims to identify therapeutic targets for metabolic syndrome and liver fibrosis.
Figures are computed from collected data and may differ slightly.
Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high
Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that
Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.
Skeletal muscle is involved in the homeostasis of glucose and lipid metabolism. We hypothesized that the skeletal muscle produces and secretes bioactive factor(s), similar to adipocytokines secreted by fat tissue. Here, we report the identification of a novel secretory factor, musclin, by signal sequence trap of mouse skeletal muscle cDNAs. Musclin cDNA encoded 130 amino acids, including NH(2)-terminal 30-amino acid signal sequence. Musclin protein contained a region homologous to natriuretic pe
Hepatic fibrosis in nonalcoholic steatohepatitis (NASH) and cirrhosis determines patient prognosis; however, effective treatment for fibrosis has not been established. Oxidative stress and inflammation activate hepatic stellate cells (HSCs) and promote fibrosis. In contrast, cellular senescence inhibits HSCs' activity and limits fibrosis. The aim of this study was to explore the effect of IGF-I on NASH and cirrhotic models and to clarify the underlying mechanisms. We demonstrate that IGF-I signi
Small heterodimer partner (SHP, NR0B2) is an atypical orphan nuclear receptor that inhibits transcriptional activation by several other nuclear receptors. We recently reported that mutations in the SHP gene are associated with insulin resistance. In the present study, we demonstrated that the SHP gene is expressed in adipose tissues. A reporter gene assay showed that a gene product of SHP increased the transcriptional activation of peroxisome proliferator-activated receptor (PPAR) gamma. SHP-med
Objective The production of uric acid in murine white adipose tissue (mWAT), and that such production was augmented in obese mice, was recently reported. However, little is known about the secretion of metabolites associated with purine catabolism in human WAT (hWAT). The present study analyzed this in hWAT. Methods Freshly isolated hWAT and mWAT were cultured. The secretion of metabolites associated with purine catabolism was measured. Tissue distribution profiles of genes associated with purin
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