Heme Oxygenase 1 and 2 Differentially Regulate Glucose Metabolism and Adipose Tissue Mitochondrial Respiration: Implications for Metabolic Dysregulation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Yao, Hongwei; Peterson, Abigail L.; Li, Jie; Xu, Haiyan; Dennery, Phyllis A.
Abstract
Heme oxygenase (HO) consists of inducible (HO-1) and constitutive (HO-2) isoforms that are encoded by Hmox1 and Hmox2 genes, respectively. As an anti-inflammatory and antioxidant molecule, HO participates in the development of metabolic diseases. Whether Hmox deficiency causes metabolic abnormalities under basal conditions remains unclear. We hypothesized that HO-1 and HO-2 differentially affect global and adipose tissue metabolism. To test this hypothesis, we determined insulin sensitivity, glucose tolerance, energy expenditure, and respiratory exchange ratio in global Hmox1(-/-) and Hmox2(-/-) mice. Body weight was reduced in female but not male Hmox1(-/-) and Hmox2(-/-) mice. Reduced insulin sensitivity and physical activity were observed in Hmox1(-/-) but not Hmox2(-/-) mice. Deletion of either Hmox1 or Hmox2 had no effects on glucose tolerance, energy expenditure or respiratory exchange ratio. Mitochondrial respiration was unchanged in gonadal fat pads (white adipose tissue, WAT) of Hmox1(-/-) mice. Hmox2 deletion increased proton leak and glycolysis in gonadal, but not interscapular fat tissues (brown adipose tissue, BAT). Uncoupling protein and Hmox1 genes were unchanged in gonadal fat pads of Hmox2(-/-) mice. Conclusively, HO-1 maintains insulin sensitivity, while HO-2 represses glycolysis and proton leak in the WAT under basal condition. This suggests that HO-1 and HO-2 differentially modulate metabolism, which may impact the metabolic syndrome.
Association between a heme oxygenase-2 genetic variant and risk of Parkinson's disease in Han Chinese
NEUROSCIENCE LETTERS
Authors: Tian, Sijia; Yang, Xinglong; Zhao, Quanzhen; Zheng, Jinhua; Huang, Hongyan; Chen, Yalan; An, Ran; Xu, Yanming
Abstract
Studies have reported conflicting results about possible associations between variants in heme oxygenase (HMOX) genes and risk of Parkinson's disease (PD) in Caucasians, and little is known about these associations in Asians. We genotyped the single-nucleotide polymorphisms (SNPs) rs2071746 and rs2071747 in HMOX1 and rs1051308 in HMOX2 in 583 Han Chinese with PD and 627 healthy controls using a customized 2 x 48-Plex SNP Scan (TM) kit. Frequencies of genotypes and minor alleles were similar between patients and controls for rs2071746 and rs2071747, but different for rs1051308(P = 0.004, OR 1.705, 95%CI 1.191-2.442 for genotypes; P = 0.009, OR 1.249, 95%CI 1.037-1.476 for alleles). Our results suggest that rs1051308 is associated with risk of developing PD in Han Chinese, and further studies involving various ethnicities are needed to validate the association. (C) 2017 Published by Elsevier Ireland Ltd.