Anti-hypoxia works as anti-obesity… New obesity treatment is found???
It is just recently published in PlosOne journal that Shin et al. successfully reduce body weight of diet induced obesity using HIF-1 alpha antisense oligonucleotide or ASO. HIF-1 alpha or hypoxia inducible factor-1 is protein that expressed when oxygen in the cell or tissue are low. This protein is sensitive to oxigen level in human body.
Hypoxia in obesity is a new research field with a lot of potentials. These studies were started when scientists found the fact that hypoxia occured in adipose tissues of obese humans and animal model. Earlier this year, a research group from United Kingdom shown a promising result from their microarray analysis that hypoxia in adipocyte induced changes in lipolysis and fat oxidation pathway. Mice model has also been used in the other studies showing that knock out HIF-1 alpha is able to protect against obesity while constitutive activation could lead to mild obesity.
In the report, Shin shown that inducing ASO to a mice model could reduce expression of HIF-1 alpha in several area including liver, brown fat; epididymal fat and omental fat. Not only be able to decrease hypoxia marker, ASO administration also be able to reduce body weight and adiposity significantly. This action then followed by changes in energy expenditure. And since food intake and physical activity were not different in control and treatment group, it is assumed that weight reduction is due to increment of energy expenditure.
Authors tried to find out the effect of this treatment to metabolic changes. Interestingly, they shown that insulin and glucose level are reduce thus metabolism switched into fat oxidation. This is a good news because energy effiency was be reduce and more fat used as the source of energy.
Not only on fat metabolism. Treatment in hypoxia also be able to change expression of molecules that are related to adipocyte cells. In this case serum leptin, total cholesterol and adiponectin are successfully decreased after treatment. The ASO treatment is also be able to decrease enzyme in lipid biosynthesi in the liver.
This study is really open the possibility of treatment for weigh lost in the future using changes in hypoxia. However, following studies are really needed to confirm this finding. More importantly, molecular mechanism beneath the anti hypoxia treatment and weight lost.
Shin MK et al. Metabolic consequences of high fat diet are attenuated by suppression of HIF-1a. plosOne, 2012, (10), 46562.