New role for ceramide in hypoxia and insulin resistance
WORLD JOURNAL OF GASTROENTEROLOGY
Authors: Xia, Qing-Song; Lu, Fu-Er; Wu, Fan; Huang, Zhao-Yi; Dong, Hui; Xu, Li-Jun; Gong, Jing
Abstract
Ceramides are significant metabolic products of sphingolipids in lipid metabolism and are associated with insulin resistance and hepatic steatosis. In chronic inflammatory pathological conditions, hypoxia occurs, the metabolism of ceramide changes, and insulin resistance arises. Hypoxia-inducible factors (HIFs) are a family of transcription factors activated by hypoxia. In hypoxic adipocytes, HIF-1 alpha upregulates pla2g16 (a novel HIF-1 alpha target gene) gene expression to activate the NLRP3 inflammasome pathway and stimulate insulin resistance, and adipocyte-specific Hif1a knockout can ameliorate homocysteine-induced insulin resistance in mice. The study on the HIF-2 alpha-NEU3-ceramide pathway also reveals the role of ceramide in hypoxia and insulin resistance in obese mice. Under obesity-induced intestinal hypoxia, HIF-2 alpha increases the production of ceramide by promoting the expression of the gene Neu3 encoding sialidase 3, which is a key enzyme in ceramide synthesis, resulting in insulin resistance in high-fat diet-induced obese mice. Moreover, genetic and pathophysiologic inhibition of the HIF-2 alpha-NEU3-ceramide pathway can alleviate insulin resistance, suggesting that these could be potential drug targets for the treatment of metabolic diseases. Herein, the effects of hypoxia and ceramide, especially in the intestine, on metabolic diseases are summarized.
The relevance of HIF1A gene polymorphisms and primary hypertensive left ventricular hypertrophy in Chinese Han population
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Authors: Sheng, Z-L; Ju, C-W; Yan, G-L; Chen, Z-P; Pan, X-D; Lu, W-B; Yao, Y-Y; Ma, G-S
Abstract
INTRODUCTION: To investigate the effect of gene polymorphisms in hypoxia-inducible factor 1 alpha (HIF-1 alpha) in left ventricular hypertrophy of hypertensive patients. PATIENTS AND METHODS: A total of 583 hypertensive patients were divided into two groups, with left ventricular hypertrophy (LVH (+), 198 cases) and without left ventricular hypertrophy (LVH (-), 385 cases). Polymerase Chain Reaction restriction fragment length polymorphism was used to detect the single nucleotide gene polymorphisms rs11549465, rs11549467 and rs1957757 in HIF-1 alpha. RESULTS: The distribution differences of gene frequencies for rs11549465, rs11549467 and rs1957757 in HIF1A single nucleotide gene polymorphisms for LVH (+) and LVH (-) were statistically significant (p<0.05). The T allele of rs11549465 loci and the G allele of rs11549467 loci increased the risk of LVH, related to the increased plasma expression of HIF-1 alpha ( (p<0.05). CONCLUSIONS: Gene polymorphism of HIF-1 alpha were related to primary hypertensive left ventricular hypertrophy, and the expression of rs11549467 correlated with the increasing concentration of plasma HIF-1 alpha.