Sex hormones are likely to be involved in sex differences in adipose tissue distribution. To test whether estrogen regulates genes expressed in the adipose tissue in a site-specific manner, we studied the effect of exogenous estradiol on the gene expression in visceral and subcutaneous adipose tissues of male ob/ob mice. We screened genes expressed in a site- and sex-specific manner, and genes that were affected by exogenous estradiol by DNA chip analysis. They were verified by real-time PCR. Myosin heavy chain 2B (Myh4) and phosphoglycerate mutase muscle-specific subunit (Pgam) were expressed specifically in the subcutaneous adipose tissue, and uroplakin IIIb (UP3) was expressed specifically in the visceral adipose tissue. DEAD-box Y RNA helicase (DBY) and eukaryotic initiation factor 2 gamma Y (eIF2γ Y) were expressed only in male adipose tissue. X-chromosome inactive specific transcript (Xist) was expressed only in female adipose tissue. When estradiol was subcutaneously administrated to male mice, the expression of monocyte-chemoattractant protein-1 (MCP-1) and androgen receptor (AR) genes was regulated in a site-specific manner. The difference in the amount of estrogen receptor did not account for the site-specific effect of estrogen. Our findings show that estrogen affects the expression of some adipocyte genes in a site-specific manner.

Luseogliflozin, a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), was previously shown to improve the blood glucose and hemoglobin A1c (HbA1c) levels of patients with type 2 diabetes in a clinical setting. Although patients with type 2 diabetes often have hepatic impairment, few reports have been published concerning the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes accompanied by hepatic impairment. The present study was undertaken to evaluate the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes divided into 2 groups according to hepatic function parameters (a normal group and an elevated group). In this study, luseogliflozin significantly improved both HbA1c and body weight to similar extents in both the normal group and the elevated group, accompanied by marked reductions in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GTP) levels. These results suggested that luseogliflozin can be safely used in patients with type 2 diabetes who also exhibit hepatic impairment. The results additionally suggest the possibility that luseogliflozin might be capable of alleviating hepatic impairment in patients with type 2 diabetes.

Objective: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemia agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, so this combination required careful administration for patients. In the present study, we evaluated the effects of combination therapy of pemafibrate, a novel fibrate and statins. Methods: We administered pemafibrate for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and examined the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group. Results: In the combination group, a decrease in serum total cholesterol levels was observed after 6 months of pemafibrate treatment compared to baseline, along with an increase in HDL-cholesterol. While serum triglyceride level was reduced, HbA1c level was elevated in both the groups. Serum creatinine kinase level, which is an indicator of myopathy, was lowered in the combination group. In addition, a decrease in γ-glutamyl transpeptidase, a parameter of hepatic dysfunction, was observed in the combination group. Conclusion: The statin-pemafibrate combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.