Erythropoietin as a possible mechanism for the effects of intermittent hypoxia on bodyweight, serum glucose and leptin in mice.
The aim of this study was to determine the effects of intermittent hypoxia training (IHT), with and without fatty-diet, on bodyweight, serum glucose, leptin, insulin, and their receptors, and to test whether erythropoietin (EPO) mediates these effects.


METHODS
Kunming mice were divided into four groups. 1: untreated control; 2: IHT; 3: fatty-diet; 4: fatty-diet and IHT. After 40 days exposure to IHT, the bodyweight, serum glucose, serum leptin, insulin and EPO were measured by ELISA. Liver leptin and insulin receptors were quantified. A separate set of mice were treated with several doses of EPO (0-320 U/kg i.p.) for 5 days. In addition, human hepatic cell lines were treated with EPO for 24h and the expression of genes OB-Ra, OB-Rb and IR were measured using RT-PCR.


RESULTS
IHT reduced bodyweight and serum glucose, with corresponding increases in the serum levels of leptin, insulin, EPO and expression of leptin and insulin receptors in liver. Repeated EPO treatment increased serum leptin concentration, but had no effects on insulin levels. The expression of the genes OB-Ra, OB-Rb and IR were increased after EPO treatment.


CONCLUSIONS
We postulate that, in mice, IHT reduces bodyweight and serum glucose by increasing EPO synthesis which secondarily increases leptin and insulin production in liver.
Qin
Ling
L
Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiang
Yang
Y
Song
Zhi
Z
Jing
Ran
R
Hu
Chengping
C
Howard
Susan T
ST
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000503:physiopathology*; D020738:Leptin / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011972:Receptor, Insulin / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D020738:Leptin; D011994:Recombinant Proteins; D004921:Erythropoietin; D011972:Receptor, Insulin