Unveiling the aetiology of insulin resistance
Insulin resistance is a common denominator in many metabolic-related diseases and obesity. However, the mechanism that causes insulin resistance is not completely understood. Emerging evidence indicates that the presence of certain pro-inflammatory cytokines such as hepatocyte growth factor (HGF) in adipose tissue is tightly associated with obese subjects and the development of metabolic disease. Although the role of HGF in the activation of glucose metabolism and in the inhibition of fatty acid oxidation is well established, little is known about its role in insulin resistance. Seeking to address this, the EU-funded 'Hepatocyte growth factor and insulin resistance' (HGF-INSR) consortium generated transgenic mice expressing HGF in skeletal muscle and mice lacking the HGF receptor in skeletal muscle. Looking at the impact of HGF in these mice, they observed reduced plasma insulin levels and improved glucose tolerance, despite similar body weight. The results were even more striking when HGF was overexpressed in the muscle of obese mice, with improved total body glucose metabolism and insulin sensitivity. The consortium worked under the hypothesis that HGF improves insulin sensitivity. They also performed anthropometric measurements in normal and obese children to find an association between plasma HGF levels and insulin resistance in obese children. HGF levels were also higher in pre-term neonates, suggesting a potential role in foetal maturity. To understand the association between maternal obesity and foetal metabolism, scientists measured the levels of HGF in amniotic fluid. Their findings clearly supported a mechanistic link between HGF with glucose and lipid metabolism in neonates. They suggest that HGF modifies the availability of nutrients to the foetus, thereby increasing the risk of metabolic diseases such as obesity and diabetes later in life. Taken together, the results of the HGF-INSR study underscore the importance of HGF in insulin resistance and the development of metabolic diseases. Furthermore, they indicate that HGF could be reliably used as a diagnostic marker for predicting obesity or diabetes.
Keywords
Insulin resistance, obesity, hepatocyte growth factor, HGF, metabolic disease
