Macrophage HIF-1α increases liver tumor

Aims/Introduction: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of liver cancer. Recently, it was reported that hypoxia‐inducible factor‐1α (HIF‐1α) is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity‐ and diabetes‐associated liver cancer using macrophage‐specific HIF‐1α knockout (KO) mice. Materials and Methods: To induce liver cancer in the mice, diethylnitrosamine, a chemical carcinogen, was used. Both KO mice and wild‐type littermates were fed either a high‐fat diet (HFD) or normal chow. They were mainly analyzed 6 months after HFD feeding. Results: Development of liver cancer after HFD feeding was 45% less in KO mice than in wild‐type littermates mice. Phosphorylation of extracellular signal‐regulated kinase 2 was also lower in the liver of KO mice. Those effects of HIF‐1α deletion in macrophages were not observed in normal chow‐fed mice. Furthermore, the size of liver tumors did not differ between KO and wild‐type littermates mice, even those on a HFD. These results suggest that the activation of macrophage HIF‐1α by HFD is involved not in the growth, but in the development of liver cancer with the enhanced oncogenic extracellular signal‐regulated kinase 2 signaling in hepatocytes. Conclusions: The activation of macrophage HIF‐1α might play important roles in the development of liver cancer associated with diet‐induced obesity and diabetes

No association of the Trp 64 Arg mutation of the β3-adrenergic receptor gene with obesity, type 2 diabetes mellitus, hyperlipidemia, and hypertension in Japanese patients with schizophrenia

This study was conducted to address the question of whether the β3-adrenergic receptor gene mutation (Trp 64 Arg) is associated with metabolic disease in Japanese patients with schizophrenia. Methods : In a cross-sectional study, 89 participants were grouped into three genotypes. The 64 Arg allelic frequency in patients with or without metabolic disease was analyzed. Anthropometrics variables and biochemical parameters were compared among the genotypes. Results : The 64 Arg allele, which had a frequency of 0.22, was not associated with obesity, type 2 diabetes mellitus, dyslipidemias, or hypertension. No significant differences among the genotypes were found in current age, age at diagnosis with schizophrenia, body mass index, waist-hip ratio, plasma glucose, plasma insulin, triglycerides, free fatty acids. Patients with the 64 Arg allele had greater 24-h excretion of norepinephrine than those lacking the variant (p=0.019). Conclusion : The 64Arg allelic mutation is not associated with obesity, type 2 diabetes mellitus, lipid metabolism dysfunction, or hypertension in Japanese patients with schizophrenia